Down syndrome (Trisomy 21)

Epidemiology and Genetics

Epidemiology

• Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 1 in 700 live births
• ↑ Risk with ↑ maternal age:
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: 1 in 100 with maternal age of 40 years
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: approximately 1 in 30 with maternal age of 45 years
  • Incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency: approximately 1 in 6 with maternal age of 50 years
• 80% of affected children are born to women < 35 years of age—the group that has most of the children.
• One of most common autosomal chromosomal aberrations chromosomal aberrations Abnormal number or structure of chromosomes. Chromosome aberrations may result in chromosome disorders. Chromosome Testing
• Most frequent genetic cause of developmental delay
• Life expectancy Life expectancy Based on known statistical data, the number of years which any person of a given age may reasonably expected to live. Population Pyramids: approximately 50 years

Genetics Genetics Genetics is the study of genes and their functions and behaviors. Basic Terms of Genetics

There are 3 genotypes that result in Down syndrome.

• Full trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21:
  • 90%–95% of cases
  • Each cell in the body has an extra chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 21.
  • Occurs spontaneously, not inherited
  • Most commonly due to nondisjunction Nondisjunction The failure of homologous chromosomes or chromatids to segregate during mitosis or meiosis with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none. Basic Terms of Genetics in meiosis Meiosis The creation of eukaryotic gametes involves a DNA replication phase followed by 2 cellular division stages: meiosis I and meiosis II. Meiosis I separates homologous chromosomes into separate cells (1n, 2c), while meiosis II separates sister chromatids into gametes (1n, 1c). Meiosis I (70%) 
  • May also be due to nondisjunction Nondisjunction The failure of homologous chromosomes or chromatids to segregate during mitosis or meiosis with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none. Basic Terms of Genetics in meiosis Meiosis The creation of eukaryotic gametes involves a DNA replication phase followed by 2 cellular division stages: meiosis I and meiosis II. Meiosis I separates homologous chromosomes into separate cells (1n, 2c), while meiosis II separates sister chromatids into gametes (1n, 1c). Meiosis II (20%)
  • Nondisjunction Nondisjunction The failure of homologous chromosomes or chromatids to segregate during mitosis or meiosis with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none. Basic Terms of Genetics typically of maternal origin
  • Rarely due to paternal nondisjunction Nondisjunction The failure of homologous chromosomes or chromatids to segregate during mitosis or meiosis with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none. Basic Terms of Genetics during spermatogenesis Spermatogenesis The process of germ cell development in the male from the primordial germ cells, through spermatogonia; spermatocytes; spermatids; to the mature haploid spermatozoa. Gametogenesis (approximately 5%)
  • Karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System: 47,XX,+21 (girls) and 47,XY,+21 (boys)
• Translocation trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21: 
  • Approximately 2%–4% of all cases
  • Part or an extra or a whole extra chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 21 is attached (translocated) to another acrocentric chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics (often chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 14).
  • Translocation may occur spontaneously or be inherited from an unaffected parent with balanced translocation (parent is carrier Carrier Vaccination).
  • Advanced maternal age is not a risk factor for translocation trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21.
  • Balanced Robertsonian translocation Robertsonian translocation Patau Syndrome (Trisomy 13):
    • Long arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 21 is translocated and fused to long arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 14 (short arms of both chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure are deleted).
    • Karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System: 45,XX,t(21;14) or 45,XY,t(21;14)
    • Necessary genetic material resides on long arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy of chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure; all needed genetic material is present, thus the phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics is normal.
  • Unbalanced translocation: 
    • Results in trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21 phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics
    • 2 normal copies of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 21 are present along with translocated t(21;14) chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics, resulting in 3 copies of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 21.
    • Karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System: 46,XX,+21,t(21;14) or 46XY,+21,t(21;14)
    • Spontaneous t(21;14) translocations are typically of maternal origin.
    • Risk of fetus with Down syndrome is 25% in parent who is a carrier Carrier Vaccination of the t(21;14) balanced translocation.
  • A t(21;21) Robertsonian translocation Robertsonian translocation Patau Syndrome (Trisomy 13) also occurs infrequently between homologous chromosomes Homologous chromosomes Basic Terms of Genetics (in most cases, t(21;21) is actually an isochromosome (dup21q), meaning 1 arm Arm The arm, or “upper arm” in common usage, is the region of the upper limb that extends from the shoulder to the elbow joint and connects inferiorly to the forearm through the cubital fossa. It is divided into 2 fascial compartments (anterior and posterior). Arm: Anatomy of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 21 duplicates itself, creating a partial trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations in and of itself):
    • Occurs spontaneously
    • Isochromosome (dup21q) is equally likely to be of maternal or paternal origin.
    • Robertsonian translocation Robertsonian translocation Patau Syndrome (Trisomy 13) typically of maternal origin
    • Risk of fetus with Down syndrome rises to 100% in carriers Carriers The Cell: Cell Membrane of t(21;21) translocation.
• Mosaic trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21: 
  • 1%–2% of all cases
  • Simultaneous existence of normal cell line with normal number of chromosomes Chromosomes In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. DNA Types and Structure and another cell line with 3 copies of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 21 ( trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21)
  • Caused by nondisjunction Nondisjunction The failure of homologous chromosomes or chromatids to segregate during mitosis or meiosis with the result that one daughter cell has both of a pair of parental chromosomes or chromatids and the other has none. Basic Terms of Genetics during mitosis Mitosis A type of cell nucleus division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. Cell Cycle
  • Timing of mitotic error Error Refers to any act of commission (doing something wrong) or omission (failing to do something right) that exposes patients to potentially hazardous situations. Disclosure of Information affects ratio of trisomic to normal cells.
  • Phenotype Phenotype The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics depends on ratio of normal cells to trisomic cells.
  • Karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System: 46,XX/47,XX,+21 or 46,XY/47,XY,+21

Clinical Presentation

Craniofacial

• Brachycephaly (flattened back of skull Skull The skull (cranium) is the skeletal structure of the head supporting the face and forming a protective cavity for the brain. The skull consists of 22 bones divided into the viscerocranium (facial skeleton) and the neurocranium. Skull: Anatomy)
• Almond-shaped eyes
• Upslanting palpebral fissures
• Epicanthal folds
• Ocular hypertelorism Hypertelorism Abnormal increase in the interorbital distance due to overdevelopment of the lesser wings of the sphenoid. DiGeorge Syndrome (↑↑ distance between eyes)
• Brushfield spots (small white or grayish-brown spots on periphery of iris)
• Flattened, broad nasal bridge
• Low-set, small, rounded, folded, and/or dysplastic ears
• Small mouth and chin Chin The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. Melasma
• High-arched palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy (roof of mouth)
• Abnormal teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth: Anatomy
• Large, protruding, and/or fissured tongue Tongue The tongue, on the other hand, is a complex muscular structure that permits tasting and facilitates the process of mastication and communication. The blood supply of the tongue originates from the external carotid artery, and the innervation is through cranial nerves. Lips and Tongue: Anatomy

Ocular

High prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of ocular disorders: Frequency increases with age.

• Refractive errors Refractive errors By refraction, the light that enters the eye is focused onto a particular point of the retina. The main refractive components of the eye are the cornea and the lens. When the corneal curvature, the refractive power of the lens, does not match the size of the eye, ametropia or a refractive error occurs. Refractive Errors, such as myopia Myopia Refractive Errors, hyperopia Hyperopia Refractive Errors, and astigmatism Astigmatism Unequal curvature of the refractive surfaces of the eye. Thus a point source of light cannot be brought to a point focus on the retina but is spread over a more or less diffuse area. This results from the radius of curvature in one plane being longer or shorter than the radius at right angles to it. . Refractive Errors (approximately 35%–76%)
• Strabismus Strabismus Strabismus is the misalignment of the eyes while fixating the gaze on an object. Strabismus can be idiopathic, but it may also be caused by cerebral palsy, uncorrected refractive errors, and extraocular muscle or cranial nerve dysfunction. Strabismus (crossed eyes) 
• Nystagmus Nystagmus Involuntary movements of the eye that are divided into two types, jerk and pendular. Jerk nystagmus has a slow phase in one direction followed by a corrective fast phase in the opposite direction, and is usually caused by central or peripheral vestibular dysfunction. Pendular nystagmus features oscillations that are of equal velocity in both directions and this condition is often associated with visual loss early in life. Albinism 
• Cataracts
• Corneal opacities
• Glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
• Keratonus (abnormal shape and thinning of cornea Cornea The transparent anterior portion of the fibrous coat of the eye consisting of five layers: stratified squamous corneal epithelium; bowman membrane; corneal stroma; descemet membrane; and mesenchymal corneal endothelium. It serves as the first refracting medium of the eye. Eye: Anatomy)

Auditory

• Recurrent otitis media
• Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss:
  • May be congenital Congenital Chorioretinitis or secondary to otitis media
  • Conductive hearing loss Conductive hearing loss Hearing loss due to interference with the mechanical reception or amplification of sound to the cochlea. The interference is in the outer or middle ear involving the ear canal; tympanic membrane; or ear ossicles. Hearing Loss most common, but may also be sensorineural or mixed
  • May be unilateral or bilateral

Musculoskeletal

• Hypotonia Hypotonia Duchenne Muscular Dystrophy 
• Short neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess with excessive skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions at nape
• Dysplasia Dysplasia Cellular Adaptation of middle phalanx of 5th finger
• Single transverse palmar crease
• Shortened and broad hands and feet
• Separation of first and second toes (sandal gap)
• Hypermobility of joints
• Atlantoaxial instability (ligamentous instability between atlas Atlas The first cervical vertebra. Vertebral Column: Anatomy C1 and axis Axis The second cervical vertebra. Vertebral Column: Anatomy C2 vertebrae)
• Clinodactyly (abnormal curvature of finger, typically inward curve of 5th finger)
• Brachydactyly (abnormal shortness of fingers or toes)
• Diastasis recti
• Surplus ribs Ribs A set of twelve curved bones which connect to the vertebral column posteriorly, and terminate anteriorly as costal cartilage. Together, they form a protective cage around the internal thoracic organs. Chest Wall: Anatomy
• Abnormal vertebral bodies
• Pelvic dysplasia Dysplasia Cellular Adaptation with leveled angle of acetabulum and ilium

Cardiovascular

• Congenital Congenital Chorioretinitis heart defects present in approximately 50% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, with > 20% having more than 1 anomaly:
  • Atrioventricular septal defect (approximately 40%)
  • Ventricular septal defect Ventricular Septal Defect Tetralogy of Fallot (approximately 30%)
  • Isolated atrial septal defects (approximately 15%)
  • Tetralogy of Fallot Tetralogy of Fallot Tetralogy of Fallot is the most common cyanotic congenital heart disease. The disease is the confluence of 4 pathologic cardiac features: overriding aorta, ventricular septal defect, right ventricular outflow obstruction, and right ventricular hypertrophy. Tetralogy of Fallot 
  • Patent ductus arteriosus Ductus arteriosus A fetal blood vessel connecting the pulmonary artery with the descending aorta. Patent Ductus Arteriosus (PDA) 
• Valve abnormalities found in adolescents/adults, most commonly mitral valve prolapse Mitral valve prolapse Abnormal protrusion or billowing of one or both of the leaflets of mitral valve into the left atrium during systole. This allows the backflow of blood into left atrium leading to mitral valve insufficiency, systolic murmurs, or cardiac arrhythmia. Mitral Valve Prolapse and aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD) 
• Pulmonary hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension also common (> 25%) and may be transient or persistent

Gastrointestinal

• GI tract anomalies occur in approximately 5% of cases:
  • Duodenal atresia Atresia Hypoplastic Left Heart Syndrome (HLHS)/ stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) + annular Annular Dermatologic Examination pancreas Pancreas The pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue. Pancreas: Anatomy most common
  • Atresia Atresia Hypoplastic Left Heart Syndrome (HLHS) of esophagus Esophagus The esophagus is a muscular tube-shaped organ of around 25 centimeters in length that connects the pharynx to the stomach. The organ extends from approximately the 6th cervical vertebra to the 11th thoracic vertebra and can be divided grossly into 3 parts: the cervical part, the thoracic part, and the abdominal part. Esophagus: Anatomy + tracheoesophageal fistula Fistula Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. Anal Fistula
  • Atresia Atresia Hypoplastic Left Heart Syndrome (HLHS) of anus 
  • Rectal prolapse Rectal prolapse Rectal prolapse, also known as rectal procidentia, is the protrusion of rectal tissue through the anus. The tissue may include just the mucosa or the full thickness of the rectal wall. Common risk factors include chronic straining, constipation, bowel motility disorders, and weakening of the pelvic floor muscles. Rectal Prolapse
  • Malformation of bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy duct 
• Umbilical/inguinal hernia Hernia Protrusion of tissue, structure, or part of an organ through the bone, muscular tissue, or the membrane by which it is normally contained. Hernia may involve tissues such as the abdominal wall or the respiratory diaphragm. Hernias may be internal, external, congenital, or acquired. Abdominal Hernias
• Hirschsprung’s disease ( congenital Congenital Chorioretinitis defect involving nerve cells of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy causing functional bowel obstruction Bowel obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis)
• Celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease (intolerance to gluten Gluten Prolamins in the endosperm of seeds from the triticeae tribe which includes species of wheat; barley; and rye. Celiac Disease affecting small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy)

Hematologic

• Polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma (↑ RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology) 
• Leukopenia (↓ WBCs)
• Thrombocytosis 
• Transient myeloproliferative disorder, also known as transient leukemia:
  • Found almost exclusively in newborns with Down syndrome
  • Majority asymptomatic and have spontaneous resolution within 2–3 months
  • Rarely progresses to serious condition, which can cause organ damage and death
• ↑ Risk of leukemia (ALL, AML AML Acute myeloid leukemia (AML) is a hematologic malignancy characterized by the uncontrolled proliferation of myeloid precursor cells. Seen predominantly in older adults, AML includes an accumulation of myeloblasts and a replacement of normal marrow by malignant cells, which leads to impaired hematopoiesis. Acute Myeloid Leukemia)

Endocrine

• Hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism
• Type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus

Reproductive

• Hypogonadism Hypogonadism Hypogonadism is a condition characterized by reduced or no sex hormone production by the testes or ovaries. Hypogonadism can result from primary (hypergonadotropic) or secondary (hypogonadotropic) failure. Symptoms include infertility, increased risk of osteoporosis, erectile dysfunction, decreased libido, and regression (or absence) of secondary sexual characteristics. Hypogonadism
• Cryptorchidism Cryptorchidism Cryptorchidism is one of the most common congenital anomalies in young boys. Typically, this asymptomatic condition presents during a routine well-child examination where 1 or both testicles are not palpable in the scrotum. Cryptorchidism ( undescended testes Undescended testes A developmental defect in which a testis or both testes failed to descend from high in the abdomen to the bottom of the scrotum. Testicular descent is essential to normal spermatogenesis which requires temperature lower than the body temperature. Cryptorchidism can be subclassified by the location of the maldescended testis. Familial Juvenile Polyposis)
• Impaired fertility, more so in men

Neurologic

• ↑ Risk of early-onset Alzheimer disease Early-Onset Alzheimer Disease Alzheimer Disease (typically by age 40)
• ↑ Risk of development of epilepsy Epilepsy Epilepsy is a chronic brain disorder marked by recurrent and unprovoked seizures. These seizures can be classified as focal or generalized and idiopathic or secondary to another condition. Clinical presentation correlates to the classification of the epileptic disorder. Epilepsy

Psychiatric/behavioral

• Developmental delay is universal.
• Cognitive impairment is often present.
• ↑ Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of behavioral disorders: 
  • ADHD ADHD Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. Attention Deficit Hyperactivity Disorder
  • Conduct/oppositional disorder
  • Aggressive behaviors
• Depression and aggressive behavior most common in adults
• Autism diagnosed as comorbidity in about 7% of cases
• Down syndrome is a disintegrative disorder.
  • New or worsening autism-like symptoms in school-aged children
  • Cognitive decline/ dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders
  • New-onset insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia

Development

• Impaired development noted in 1st year of life: 
  • Impaired motor Motor Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology development: milestones achieved at approximately twice the normal age
  • Impaired language development: Average age for 1st word is 18 months.
• Cognitive impairment varies from mild to severe, with most having mild to moderate intellectual disability Disability Determination of the degree of a physical, mental, or emotional handicap. The diagnosis is applied to legal qualification for benefits and income under disability insurance and to eligibility for social security and workman’s compensation benefits. ABCDE Assessment.
• Growth retardation Growth Retardation Failure of a fetus to attain expected growth. Fetal Alcohol Spectrum Disorder/↓ growth rate

Other associated conditions

• Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
• Sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea 
• ↑ Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, particularly respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

Diagnosis

Prenatal diagnosis

Screening Screening Preoperative Care is recommended prior to 20th week of gestation.

• 1st-trimester combined test at 11th–13th week detects < 90% of cases: 
  • Maternal serum testing:
    • ↑ β-hCG
    • ↓ Pregnancy-associated plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products protein A
  • Ultrasound:
    • ↑ Nuchal translucency Nuchal translucency A prenatal ultrasonography measurement of the soft tissue behind the fetal neck. Either the translucent area below the skin in the back of the fetal neck (nuchal translucency) or the distance between occipital bone to the outer skin line (nuchal fold) is measured. Obstetric Imaging measurement ( edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema of posterior neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess)
    • Absent or hypoplastic nasal bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types
    • Shortened long bones Long bones Length greater than width. Bones: Structure and Types ( humerus Humerus Bone in humans and primates extending from the shoulder joint to the elbow joint. Arm: Anatomy, femur)
    • Shortened middle phalanges Phalanges Bones that make up the skeleton of the fingers, consisting of two for the thumb, and three for each of the other fingers. Hand: Anatomy of 5th digits with abnormal curvature
• 2nd-trimester triple test (triple screen) between 16th and 20th weeks:
  • ↑ β-hCG
  • ↓ α-fetoprotein
  • ↓ Free estriol Estriol A hydroxylated metabolite of estradiol or estrogen that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During pregnancy, a large amount of estriol is produced by the placenta. Isomers with inversion of the hydroxyl group or groups are called epiestriol. Noncontraceptive Estrogen and Progestins
• 2nd-trimester quadruple test (quad-screen) between 15th and 18th weeks:
  • ↓ Free estriol Estriol A hydroxylated metabolite of estradiol or estrogen that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During pregnancy, a large amount of estriol is produced by the placenta. Isomers with inversion of the hydroxyl group or groups are called epiestriol. Noncontraceptive Estrogen and Progestins
  • ↓ α-fetoprotein 
  • ↑ Inhibin A Inhibin A Glycoproteins that inhibit pituitary follicle stimulating hormone secretion. Inhibins are secreted by the sertoli cells of the testes, the granulosa cells of the ovarian follicles, the placenta, and other tissues. Inhibins and activins are modulators of follicle stimulating hormone secretions; both groups belong to the TGF-beta superfamily, as the transforming growth factor beta. Inhibins consist of a disulfide-linked heterodimer with a unique alpha linked to either a beta a or a beta B subunit to form inhibin a or inhibin b, respectively. Menstrual Cycle
  • ↑ β-hCG
• Sequential Sequential Computed Tomography (CT) integrated test: combination of 1st-trimester combined test and 2nd-trimester quadruple test
• Full integrated test between 10th and 13th weeks includes measurement of maternal serum pregnancy-associated plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products protein A and nuchal translucency Nuchal translucency A prenatal ultrasonography measurement of the soft tissue behind the fetal neck. Either the translucent area below the skin in the back of the fetal neck (nuchal translucency) or the distance between occipital bone to the outer skin line (nuchal fold) is measured. Obstetric Imaging
• Cell-free fetal DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure test may be done any time after 10 weeks of gestation.
  • Fetal DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure is isolated from maternal blood and evaluated for chromosomal abnormalities
  • Noninvasive procedure for fetus
  • May be more accurate than traditional screening Screening Preoperative Care tests
  • Also tests for sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria of baby
• Diagnostic tests Diagnostic tests Diagnostic tests are important aspects in making a diagnosis. Some of the most important epidemiological values of diagnostic tests include sensitivity and specificity, false positives and false negatives, positive and negative predictive values, likelihood ratios, and pre-test and post-test probabilities. Epidemiological Values of Diagnostic Tests: 
  • Indicated if: 
    • Positive screening Screening Preoperative Care test
    • Previous pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care with child with trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 21
    • Known chromosomal translocation or aberration in parent
  • Procedures:
    • Chorionic villus sampling: takes sample of placenta Placenta A highly vascularized mammalian fetal-maternal organ and major site of transport of oxygen, nutrients, and fetal waste products. It includes a fetal portion (chorionic villi) derived from trophoblasts and a maternal portion (decidua) derived from the uterine endometrium. The placenta produces an array of steroid, protein and peptide hormones (placental hormones). Placenta, Umbilical Cord, and Amniotic Cavity for testing between 10th and 13th weeks
    • Amniocentesis Amniocentesis Percutaneous transabdominal puncture of the uterus during pregnancy to obtain amniotic fluid. It is commonly used for fetal karyotype determination in order to diagnose abnormal fetal conditions. Polyhydramnios: samples amniotic fluid Amniotic fluid A clear, yellowish liquid that envelopes the fetus inside the sac of amnion. In the first trimester, it is likely a transudate of maternal or fetal plasma. In the second trimester, amniotic fluid derives primarily from fetal lung and kidney. Cells or substances in this fluid can be removed for prenatal diagnostic tests (amniocentesis). Placenta, Umbilical Cord, and Amniotic Cavity for testing between 15th and 20th weeks
    • Percutaneous umbilical blood sampling: blood sample from umbilical cord Umbilical cord The flexible rope-like structure that connects a developing fetus to the placenta in mammals. The cord contains blood vessels which carry oxygen and nutrients from the mother to the fetus and waste products away from the fetus. Placenta, Umbilical Cord, and Amniotic Cavity between 18th and 22nd weeks (most accurate diagnosis during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care)
  • Risks include bleeding, infection, fetal injury, and, rarely, fetal loss.
• Fetal karyotyping Karyotyping Mapping of the karyotype of a cell. Chromosome Testing is confirmatory.

Postnatal diagnosis

• History and clinical examination
• Screening Screening Preoperative Care for associated conditions:
  • Pediatric cardiology evaluation and echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) to evaluate for congenital Congenital Chorioretinitis heart disease
  • Hearing screen
  • Pediatric ophthalmology exam
  • Routine labs: CBC with differential, thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function testing, glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance screening Screening Preoperative Care 
• Confirmed via karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System analysis

Management

Given the pervasive nature of Down syndrome and the lack of a cure, the majority of management focuses on screening Screening Preoperative Care and prevention of the various clinical manifestations and complications associated with the syndrome.

Medical management

• Growth: 
  • Monitor growth throughout childhood and adolescence.
  • CDC provides specific growth charts.
• Nutrition and obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity prevention:  
  • Attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment to diet and physical activity level starting at 2 years of age
  • Monitor weight gain throughout lifespan.
  • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes and vitamin D Vitamin D A vitamin that includes both cholecalciferols and ergocalciferols, which have the common effect of preventing or curing rickets in animals. It can also be viewed as a hormone since it can be formed in skin by action of ultraviolet rays upon the precursors, 7-dehydrocholesterol and ergosterol, and acts on vitamin D receptors to regulate calcium in opposition to parathyroid hormone. Fat-soluble Vitamins and their Deficiencies supplements to minimize bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types loss
• Hearing: 
  • Hearing screens every 6 months until 5 years of age, then annually 
  • Referral to otolaryngologist if hearing screen failed
  • May require hearing aids AIDS Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. HIV Infection and AIDS or cochlear implants
• Vision Vision Ophthalmic Exam:
  • Annual exam for children with known ophthalmologic disorders
  • Prescription glasses for refractive errors Refractive errors By refraction, the light that enters the eye is focused onto a particular point of the retina. The main refractive components of the eye are the cornea and the lens. When the corneal curvature, the refractive power of the lens, does not match the size of the eye, ametropia or a refractive error occurs. Refractive Errors 
  • Unaffected children should have eye exams: 
    • Annually for ages < 5 years
    • Every 2 years for ages 5–13 
    • Every 3 years for ages > 13
• Dental: 
  • Visits every 6 months
  • Treatment and cleaning may be complicated and require sedation. 
• Cardiovascular: 
  • Continued cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) monitoring through adulthood 
  • Assess for development of mitral valve prolapse Mitral valve prolapse Abnormal protrusion or billowing of one or both of the leaflets of mitral valve into the left atrium during systole. This allows the backflow of blood into left atrium leading to mitral valve insufficiency, systolic murmurs, or cardiac arrhythmia. Mitral Valve Prolapse or aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD).
• GI:  screening Screening Preoperative Care for celiac disease Celiac disease Celiac disease (also known as celiac sprue or gluten enteropathy) is an autoimmune reaction to gliadin, which is a component of gluten. Celiac disease is closely associated with HLA-DQ2 and HLA-DQ8. The immune response is localized to the proximal small intestine and causes the characteristic histologic findings of villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. Celiac Disease beginning at 1 year of age 
• Hematologic:
  • Hemoglobin measurement annually until 13 years of age to screen for anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • If transient myeloproliferative disorders detected: 
    • Repeat CBC with differential every 3 months until 3 years of age.
    • Every 6 months for ages 3–6 years
• Endocrine: 
  • Routine thyroid Thyroid The thyroid gland is one of the largest endocrine glands in the human body. The thyroid gland is a highly vascular, brownish-red gland located in the visceral compartment of the anterior region of the neck. Thyroid Gland: Anatomy function and glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance testing
  • Thyroxine Thyroxine The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (monoiodotyrosine) and the coupling of iodotyrosines (diiodotyrosine) in the thyroglobulin. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroid Hormones for hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism treatment 
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin for type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus
• Musculoskeletal/neurologic:
  • Physical therapy Physical Therapy Becker Muscular Dystrophy for hypotonia Hypotonia Duchenne Muscular Dystrophy
  • Atlantoaxial instability: 
    • Annual screening Screening Preoperative Care with thorough neurologic evaluation for signs or symptoms of spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy injury
    • Caution playing sports and other high-risk activities (e.g., trampoline use)
    • Cervical spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy films, particularly with lateral views, starting at 3 years of age:
      • If any neurologic deficits Neurologic Deficits High-Risk Headaches detected on exam 
      • Screening Screening Preoperative Care as part of sports preparticipation exam 
      • Prior to medical procedures that require extreme head positioning 
    • If abnormalities seen on cervical spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy films → place in cervical collar, refer to pediatric neurosurgeon or pediatric orthopedic spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy surgeon, obtain cervical spine Spine The human spine, or vertebral column, is the most important anatomical and functional axis of the human body. It consists of 7 cervical vertebrae, 12 thoracic vertebrae, and 5 lumbar vertebrae and is limited cranially by the skull and caudally by the sacrum. Vertebral Column: Anatomy MRI
• Sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea:
  • Screen for symptoms beginning at 1 year of age.
  • Sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep study or pulse oximetry monitoring during sleep Sleep A readily reversible suspension of sensorimotor interaction with the environment, usually associated with recumbency and immobility. Physiology of Sleep recommended by 4 years of age.
• Reproductive: 
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care is high-risk for women with Down syndrome.
  • Contraception counseling

Surgical management

• Correction of congenital Congenital Chorioretinitis heart defects
• Correction of GI anomalies
• Rarely, surgical correction for ocular disorders (e.g., strabismus Strabismus Strabismus is the misalignment of the eyes while fixating the gaze on an object. Strabismus can be idiopathic, but it may also be caused by cerebral palsy, uncorrected refractive errors, and extraocular muscle or cranial nerve dysfunction. Strabismus, cataracts) needed to improve vision Vision Ophthalmic Exam
• Surgical fusion or stabilization for severe atlantoaxial instability 
• Adenotonsillectomy or other surgical procedures for treatment of sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea

Educational/early interventions

• Neuropsychological, developmental, educational, and behavioral assessments/screenings 
• Special education
• Speech and language therapy
• Vocational training

Others

• Supportive environment 
• Genetic counseling Genetic Counseling An educational process that provides information and advice to individuals or families about a genetic condition that may affect them. The purpose is to help individuals make informed decisions about marriage, reproduction, and other health management issues based on information about the genetic disease, the available diagnostic tests, and management programs. Psychosocial support is usually offered. Myotonic Dystrophies 
• Psychotherapy Psychotherapy Psychotherapy is interpersonal treatment based on the understanding of psychological principles and mechanisms of mental disease. The treatment approach is often individualized, depending on the psychiatric condition(s) or circumstance. Psychotherapy

Differential Diagnosis

• Trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 18 ( Edwards syndrome Edwards syndrome Edwards syndrome, or trisomy 18, is a genetic syndrome caused by the presence of an extra chromosome 18. The extra chromosome is either from 3 full copies of chromosome 18 or an additional segment of chromosome 18. As the 2nd most common trisomy, Edwards syndrome is seen in 1 out of every 5,500 live births. Edwards Syndrome (Trisomy 18)): genetic syndrome caused by presence of 3 copies of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 18: Edwards syndrome Edwards syndrome Edwards syndrome, or trisomy 18, is a genetic syndrome caused by the presence of an extra chromosome 18. The extra chromosome is either from 3 full copies of chromosome 18 or an additional segment of chromosome 18. As the 2nd most common trisomy, Edwards syndrome is seen in 1 out of every 5,500 live births. Edwards Syndrome (Trisomy 18) is the 2nd most common trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations, with predominance in girls. Characteristic features include intrauterine growth retardation Growth Retardation Failure of a fetus to attain expected growth. Fetal Alcohol Spectrum Disorder, cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) defects, clenched fists with overlapping fingers, and rocker-bottom feet Rocker-bottom feet Edwards Syndrome (Trisomy 18). Diagnosis is made by karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System analysis. No treatment is available, and most do not survive beyond 1 year of life.
• Trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations 13 ( Patau syndrome Patau syndrome Trisomy 13, or Patau syndrome, is a genetic syndrome caused by the presence of 3 copies of chromosome 13. As the 3rd most common trisomy, Patau syndrome has an incidence of 1 in 10,000 live births. Most cases of Patau syndrome are diagnosed prenatally by maternal screening and ultrasound. More than half of the pregnancies result in spontaneous abortions. Patau Syndrome (Trisomy 13)): genetic syndrome caused by presence of 3 copies of chromosome Chromosome In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. Basic Terms of Genetics 13: Patau syndrome Patau syndrome Trisomy 13, or Patau syndrome, is a genetic syndrome caused by the presence of 3 copies of chromosome 13. As the 3rd most common trisomy, Patau syndrome has an incidence of 1 in 10,000 live births. Most cases of Patau syndrome are diagnosed prenatally by maternal screening and ultrasound. More than half of the pregnancies result in spontaneous abortions. Patau Syndrome (Trisomy 13) is the 3rd most common trisomy Trisomy The possession of a third chromosome of any one type in an otherwise diploid cell. Types of Mutations. Clinical features include brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and spinal cord Spinal cord The spinal cord is the major conduction pathway connecting the brain to the body; it is part of the CNS. In cross section, the spinal cord is divided into an H-shaped area of gray matter (consisting of synapsing neuronal cell bodies) and a surrounding area of white matter (consisting of ascending and descending tracts of myelinated axons). Spinal Cord: Anatomy malformations, cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) defects, eye defects, cleft lip Cleft lip The embryological development of craniofacial structures is an intricate sequential process involving tissue growth and directed cell apoptosis. Disruption of any step in this process may result in the formation of a cleft lip alone or in combination with a cleft palate. As the most common craniofacial malformation of the newborn, the diagnosis of a cleft is clinical and usually apparent at birth. Cleft Lip and Cleft Palate/ palate Palate The palate is the structure that forms the roof of the mouth and floor of the nasal cavity. This structure is divided into soft and hard palates. Palate: Anatomy, and hypotonia Hypotonia Duchenne Muscular Dystrophy. Diagnosis is made by karyotype Karyotype The full set of chromosomes presented as a systematized array of metaphase chromosomes from a photomicrograph of a single cell nucleus arranged in pairs in descending order of size and according to the position of the centromere. Congenital Malformations of the Female Reproductive System analysis. No treatment is available, and most do not survive beyond 1 year of life.
• Zellweger syndrome Zellweger syndrome Zellweger syndrome (ZWS), also called cerebrohepatorenal syndrome, is a rare congenital peroxisome biosynthesis disorder and is considered an inborn error of metabolism. Zellweger syndrome is the most severe form of a spectrum of conditions called Zellweger spectrum disorder (ZSD), and is characterized by the reduction or absence of functional peroxisomes. Zellweger Syndrome: also called cerebrohepatorenal syndrome Cerebrohepatorenal syndrome Zellweger syndrome (ZWS), also called cerebrohepatorenal syndrome, is a rare congenital peroxisome biosynthesis disorder and is considered an inborn error of metabolism. Zellweger syndrome is the most severe form of a spectrum of conditions called Zellweger spectrum disorder (ZSD), and is characterized by the reduction or absence of functional peroxisomes. Zellweger Syndrome: Zellweger syndrome Zellweger syndrome Zellweger syndrome (ZWS), also called cerebrohepatorenal syndrome, is a rare congenital peroxisome biosynthesis disorder and is considered an inborn error of metabolism. Zellweger syndrome is the most severe form of a spectrum of conditions called Zellweger spectrum disorder (ZSD), and is characterized by the reduction or absence of functional peroxisomes. Zellweger Syndrome is a rare autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance congenital Congenital Chorioretinitis peroxisome biosynthesis Biosynthesis The biosynthesis of peptides and proteins on ribosomes, directed by messenger RNA, via transfer RNA that is charged with standard proteinogenic amino acids. Virology disorder and is considered an inborn error Error Refers to any act of commission (doing something wrong) or omission (failing to do something right) that exposes patients to potentially hazardous situations. Disclosure of Information of metabolism. Characterized by reduction or absence of functional peroxisomes Peroxisomes Microbodies which occur in animal and plant cells and in certain fungi and protozoa. They contain peroxidase, catalase, and allied enzymes. The Cell: Organelles. Clinical features are present from birth and include craniofacial and skeletal anomalies, as well as ocular disorders, hypotonia Hypotonia Duchenne Muscular Dystrophy, and seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures. No treatment is available, and most do not survive beyond 1 year of life.