Marfan Syndrome

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 5,000 live births 
• Affects men and women in all ethnic and racial groups

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

• Most commonly due to a mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in the FBN1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics on 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 15 
  • Affects the connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology protein, fibrillin-1
    • Fibrillin-1 is the main component of microfibrils, which form elastic Elastic Connective Tissue: Histology fibers in connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology.
    • Mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in FBN1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics → impaired fibrillin protein → defective microfibrils → ↓ elasticity Elasticity Resistance and recovery from distortion of shape. Skeletal Muscle Contraction in tissues
  • Affects connective tissues throughout the body:
    • Organs
    • Blood vessels 
    • Eyes 
    • 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
    • Skeletal components  
• Inheritance pattern: autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance
  • 75% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have affected parents.
  • 25% of cases are de novo mutations De novo mutations DiGeorge Syndrome ( idiopathic Idiopathic Dermatomyositis).
• Penetrance Penetrance The percent frequency with which a dominant or homozygous recessive gene or gene combination manifests itself in the phenotype of the carriers. Familial Juvenile Polyposis: complete
• Expressivity: variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables

Clinical Presentation

Musculoskeletal

• Tall stature with disproportionately long extremities:
  • ↓ upper segment to lower segment ratio (US/LS)
  • ↑ 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 span to height ratio
• Long fingers and toes (arachnodactyly):
  • Positive thumb sign (Steinberg’s sign): The distal phalanx of the adducted thumb extends beyond the ulnar border of a clenched fist palm.
  • Positive wrist sign (Walker sign): The thumb and 5th finger of the hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy overlap with each other when wrapped around the contralateral wrist. 
• Joint laxity
• Elbows may lack full extension Extension Examination of the Upper Limbs mobility Mobility Examination of the Breast.
• Vertebral column Vertebral column 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 abnormalities:
  • Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis 
  • Kyphosis Kyphosis Deformities of the spine characterized by an exaggerated convexity of the vertebral column. The forward bending of the thoracic region usually is more than 40 degrees. This deformity sometimes is called round back or hunchback. Osteoporosis 
•  Chest abnormalities:
  • Pectus excavatum Pectus Excavatum Cardiovascular Examination ( funnel chest Funnel Chest Cardiovascular Examination)
    • Sternum Sternum A long, narrow, and flat bone commonly known as breastbone occurring in the midsection of the anterior thoracic segment or chest region, which stabilizes the rib cage and serves as the point of origin for several muscles that move the arms, head, and neck. Chest Wall: Anatomy protrudes inward.
    • Looks “caved in”
  • Pectus carinatum Pectus carinatum A developmental anomaly characterized by abnormal anterior protrusion of the sternum and adjacent costal cartilage. Cardiovascular Examination ( pigeon chest Pigeon chest A developmental anomaly characterized by abnormal anterior protrusion of the sternum and adjacent costal cartilage. Cardiovascular Examination or sternal kyphosis Kyphosis Deformities of the spine characterized by an exaggerated convexity of the vertebral column. The forward bending of the thoracic region usually is more than 40 degrees. This deformity sometimes is called round back or hunchback. Osteoporosis): Sternum Sternum A long, narrow, and flat bone commonly known as breastbone occurring in the midsection of the anterior thoracic segment or chest region, which stabilizes the rib cage and serves as the point of origin for several muscles that move the arms, head, and neck. Chest Wall: Anatomy protrudes outward.
• Hindfoot valgus:
  • Heel points outward away from midline.
  • Associated with pes PES Removal of plasma and replacement with various fluids, e.g., fresh frozen plasma, plasma protein fractions (ppf), albumin preparations, dextran solutions, saline. Used in treatment of autoimmune diseases, immune complex diseases, diseases of excess plasma factors, and other conditions. Thrombotic Thrombocytopenic Purpura planus (flat foot Foot The foot is the terminal portion of the lower limb, whose primary function is to bear weight and facilitate locomotion. The foot comprises 26 bones, including the tarsal bones, metatarsal bones, and phalanges. The bones of the foot form longitudinal and transverse arches and are supported by various muscles, ligaments, and tendons. Foot: Anatomy)
• Protrusio acetabuli (acetabular protrusion)
• 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
• Characteristic facial features:
  • Dolichocephaly (↓ head width:length ratio)
  • Enophthalmos (posterior displacement Displacement The process by which an emotional or behavioral response that is appropriate for one situation appears in another situation for which it is inappropriate. Defense Mechanisms of the eyeball within the orbit Orbit The orbit is the cavity of the skull in which the eye and its appendages are situated. The orbit is composed of 7 bones and has a pyramidal shape, with its apex pointed posteromedially. The orbital contents comprise the eye, extraocular muscles, 5 cranial nerves, blood vessels, fat, the lacrimal apparatus, among others. Orbit and Extraocular Muscles: Anatomy)
  • Downslanting palpebral fissures (area between open eyelids Eyelids Each of the upper and lower folds of skin which cover the eye when closed. Blepharitis)
  • Malar hypoplasia Hypoplasia Hypoplastic Left Heart Syndrome (HLHS) (malar or zygomatic Zygomatic Either of a pair of bones that form the prominent part of the cheek and contribute to the orbit on each side of the skull. Skull: Anatomy 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 is small or absent)
  • Retrognathia (lower jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy set back further than upper jaw Jaw The jaw is made up of the mandible, which comprises the lower jaw, and the maxilla, which comprises the upper jaw. The mandible articulates with the temporal bone via the temporomandibular joint (TMJ). The 4 muscles of mastication produce the movements of the TMJ to ensure the efficient chewing of food. Jaw and Temporomandibular Joint: Anatomy)

Cardiovascular

• Aortic disease is the main cause of morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status in Marfan syndrome (MFS) patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, and is due to degeneration of the media of the vessel walls.
  • Dilation or aneurysm Aneurysm An aneurysm is a bulging, weakened area of a blood vessel that causes an abnormal widening of its diameter > 1.5 times the size of the native vessel. Aneurysms occur more often in arteries than in veins and are at risk of dissection and rupture, which can be life-threatening. Thoracic Aortic Aneurysms of the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy
    • Present in 50% of children 
    • Dilation may involve thoracic aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy, abdominal aorta Abdominal Aorta The aorta from the diaphragm to the bifurcation into the right and left common iliac arteries. Posterior Abdominal Wall: Anatomy, or root of pulmonary artery Pulmonary artery The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. Lungs: Anatomy.
    • Dilation of the aortic root present in 60%–80% of adults with MFS
  • Aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
    • Often occurs with aortic dilation 
    • Valve leaflets prevented from closing properly
    • Diastolic heart murmur on exam
  • Aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection
    • Tear in the intima (innermost layer) of the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy, allowing blood between the intima and media (middle layer)
    • Life-threatening condition
    • Presents with sudden, severe, chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain that radiates to the back
    • MFS patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship account for 50% of those with aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection under 40 years of age. 
    • ↑ risk of dissection 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 and postpartum
• 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 
  • Valve leaflets bulge (prolapse) into left atrium during heart systole Systole Period of contraction of the heart, especially of the heart ventricles. Cardiac Cycle
  • More frequently seen with ↑ age and in women
  • Systolic heart murmur and midsystolic click on exam
  • Can lead to mitral regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
• Dilation of carotid and cranial arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology 
  • Much less common
  • Berry (saccular) aneurysms are typically at the exit of the circle of Willis Circle of Willis A polygonal anastomosis at the base of the brain formed by the internal carotid, proximal parts of the anterior, middle, and posterior cerebral arteries, the anterior communicating artery and the posterior communicating arteries. Subarachnoid Hemorrhage.
  • Rupture of a cranial artery can cause subarachnoid hemorrhage Subarachnoid Hemorrhage Subarachnoid hemorrhage (SAH) is a type of cerebrovascular accident (stroke) resulting from intracranial hemorrhage into the subarachnoid space between the arachnoid and the pia mater layers of the meninges surrounding the brain. Most SAHs originate from a saccular aneurysm in the circle of Willis but may also occur as a result of trauma, uncontrolled hypertension, vasculitis, anticoagulant use, or stimulant use. Subarachnoid Hemorrhage.

Ocular

• Dislocation of the lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy (ectopia lentis)
  • Impaired supporting ciliary zonules fail to keep the lens Lens A transparent, biconvex structure of the eye, enclosed in a capsule and situated behind the iris and in front of the vitreous humor (vitreous body). It is slightly overlapped at its margin by the ciliary processes. Adaptation by the ciliary body is crucial for ocular accommodation. Eye: Anatomy in place.
  • Upward and temporal displacement Displacement The process by which an emotional or behavioral response that is appropriate for one situation appears in another situation for which it is inappropriate. Defense Mechanisms
  • Occurs in 50%–80% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Iridodonesis can be seen on inspection Inspection Dermatologic Examination ( vibration Vibration A continuing periodic change in displacement with respect to a fixed reference. Neurological Examination of the iris Iris The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers – the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. Eye: Anatomy with eye movement).
  • Seen on slit lamp Slit Lamp A microscope with a light source that can be projected into a linear beam. It allows cross-sectional viewing of the aqueous humor; conjuncteiva; cornea; eyelids; iris; and lens of the eye. Ophthalmic Exam examination
• Myopia Myopia Refractive Errors ( nearsightedness Nearsightedness Refractive Errors)
• Retinal tears or detachment
  • Often bilateral in MFS patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
  • Associated with proliferative retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome
• 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
• Early cataract Cataract Partial or complete opacity on or in the lens or capsule of one or both eyes, impairing vision or causing blindness. The many kinds of cataract are classified by their morphology (size, shape, location) or etiology (cause and time of occurrence). Neurofibromatosis Type 2 formation

Other manifestations

• 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: striae atrophicae (stretch marks) 
  • Not associated with weight changes or 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
  • Often in uncommon areas:
    • Upper arms
    • Axillary area
    • Mid and lower back
    • Thighs
• Pulmonary: emphysematous changes in the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy 
  • Lung bullae Bullae Erythema Multiforme predominantly in the upper lobes
  • ↑ risk for spontaneous pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax
• Central nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification (CNS): lumbosacral dural ectasia 
  • Dilation of the dural sac surrounding the 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
  • Symptoms: 
    • Lower back pain Back pain Back pain is a common complaint among the general population and is mostly self-limiting. Back pain can be classified as acute, subacute, or chronic depending on the duration of symptoms. The wide variety of potential etiologies include degenerative, mechanical, malignant, infectious, rheumatologic, and extraspinal causes. Back Pain
    • Radicular pain Radicular Pain Spinal Disk Herniation
    • Paresthesias Paresthesias Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation. Posterior Cord Syndrome
    • Bowel and bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess dysfunction
    • Headaches

Diagnosis

• Revised Ghent criteria
  • Complex scoring system based on the presence of characteristic Marfan syndrome manifestations
  • Requires varying combinations of: 
    • Aortic root dilatation
    • Ectopia lentis
    • FBN1 gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations
    • Systemic score > 7 (see table below)
  • The presence, or absence, of a family history Family History Adult Health Maintenance of MFS is factored in.
• Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies for the FBN1 mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations is done on a case-by-case basis if it will affect Affect The feeling-tone accompaniment of an idea or mental representation. It is the most direct psychic derivative of instinct and the psychic representative of the various bodily changes by means of which instincts manifest themselves. Psychiatric Assessment management.
• Imaging is used to evaluate for complications of MFS.
  • Radiographs → pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax, protrusio acetabuli, scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis
  • 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) (echo) → valvular and aortic root defects 
  • Computed tomography (CT) of chest, abdomen, and pelvis Pelvis The pelvis consists of the bony pelvic girdle, the muscular and ligamentous pelvic floor, and the pelvic cavity, which contains viscera, vessels, and multiple nerves and muscles. The pelvic girdle, composed of 2 “hip” bones and the sacrum, is a ring-like bony structure of the axial skeleton that links the vertebral column with the lower extremities. Pelvis: Anatomy with intravenous (IV) contrast → aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection
  • Magnetic resonance imaging (MRI) → dural ectasia, aortic dilation

Management

The management of MFS is based on the clinical manifestations. A multidisciplinary team of cardiologists, ophthalmologists, orthopedists, and cardiovascular surgeons is needed.

General

• Avoid: 
  • Caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants
  • Stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants
  • Strenuous exercise Strenuous exercise Physical activity which is usually regular and done with the intention of improving or maintaining physical fitness or health. Contrast with physical exertion which is concerned largely with the physiologic and metabolic response to energy expenditure. Cardiovascular Response to Exercise
  • Contact sports
  • Activities that entail the Valsalva maneuver Valsalva maneuver Forced expiratory effort against a closed glottis. Rectal Prolapse
  • Scuba diving
• Genetic and preconception counseling
  • 50% risk of transmission to children
  • High-risk pregnancy High-Risk Pregnancy Prenatal Care due to ↑ risk of aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection and rupture

Musculoskeletal

• Scoliosis Scoliosis Scoliosis is a structural alteration of the vertebral column characterized by a lateral spinal curvature of greater than 10 degrees in the coronal plane. Scoliosis can be classified as idiopathic (in most cases) or secondary to underlying conditions. Scoliosis treatment
  • Bracing
  • Surgery if the curve > 40 degrees
• Physical therapy Physical Therapy Becker Muscular Dystrophy
• Surgery may be needed for other skeletal anomalies (e.g., pectus deformities), if severe. 

Cardiovascular

• 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) 
  • Upon initial diagnosis and every 6–12 months
  • Evaluate and monitor aortic dilation.
  • Monitoring frequency is based on the rate of growth over time.
• Cardiac Cardiac Total Anomalous Pulmonary Venous Return (TAPVR) CT or MRI 
  • Used to confirm echo findings
  • Assess for additional aortic or vascular defects not seen on echo.
• Medications for strict blood pressure control 
  • Beta blockers 
  • Angiotensin receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blockers ( ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Angina Medication)
  • Avoid calcium channel blockers Calcium Channel Blockers Calcium channel blockers (CCBs) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBs: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers), as these may ↑ risk of aortic complications.
• Surgery
  • Elective aortic repair or replacement surgery is indicated if:
    • Diameter ≥ 50 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
    • Rapid growth
    • Family history Family History Adult Health Maintenance of dissection
    • Progressive aortic regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship considering 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
  • Surgery or medical management for aortic dissection Aortic dissection Aortic dissection occurs due to shearing stress from pulsatile pressure causing a tear in the tunica intima of the aortic wall. This tear allows blood to flow into the media, creating a “false lumen.” Aortic dissection is most commonly caused by uncontrolled hypertension. Aortic Dissection depends on whether the ascending aorta Ascending aorta Mediastinum and Great Vessels: Anatomy is involved.
  • Mitral valve Mitral valve The valve between the left atrium and left ventricle of the heart. Heart: Anatomy repair or replacement is recommended for:
    • Severe mitral regurgitation Regurgitation Gastroesophageal Reflux Disease (GERD)
    • Progressive left ventricular dilation or systolic dysfunction Systolic dysfunction Dilated Cardiomyopathy

Ocular

• Annual ophthalmologic exams
• Myopia Myopia Refractive Errors → vision Vision Ophthalmic Exam correction
• Retinal tears or detachment → photocoagulation
• Urgent ophthalmologic assessment for sudden vision Vision Ophthalmic Exam changes

Differential Diagnosis

• Homocystinuria: 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 disorder of homocysteine metabolism. Affected individuals have marfanoid body habitus and ectopia lentis, characterized by a downward and inward dislocation. Individuals may also have 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, megaloblastic 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, and thrombotic events (strokes and myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction). Measurement of homocysteine levels 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 in diagnosis. Management is via a low-methionine diet and vitamin supplementation. 
• Ehlers-Danlos syndrome Ehlers-Danlos syndrome Ehlers-Danlos syndrome (EDS) is a heterogeneous group of inherited connective tissue disorders that are characterized by hyperextensible skin, hypermobile joints, and fragility of the skin and connective tissue. Ehlers-Danlos Syndrome: an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology disorder affecting collagen Collagen A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin; connective tissue; and the organic substance of bones (bone and bones) and teeth (tooth). Connective Tissue: Histology. The syndrome has 13 subtypes, and the inheritance pattern can be autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance or recessive. The cardiovascular system, musculoskeletal system, eyes, and 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 are affected. Easy bruising Easy bruising Chédiak-Higashi Syndrome or bleeding and dental abnormalities are also seen. The syndrome is a clinical diagnosis, but genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies may be beneficial. Management is symptomatic and based on manifestations. 
• Loeys-Dietz syndrome: an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue: Histology disorder with similar presentation Presentation The position or orientation of the fetus at near term or during obstetric labor, determined by its relation to the spine of the mother and the birth canal. The normal position is a vertical, cephalic presentation with the fetal vertex flexed on the neck. Normal and Abnormal Labor to MFS but affecting a different gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics. Unlike MFS, features of hypertelorism Hypertelorism Abnormal increase in the interorbital distance due to overdevelopment of the lesser wings of the sphenoid. DiGeorge Syndrome (widely spaced eyes), split uvula Uvula A fleshy extension at the back of the soft palate that hangs above the opening of the throat. Peritonsillar Abscess, cleft 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, easy bruising Easy bruising Chédiak-Higashi Syndrome, keloid formation, and arterial tortuosity are present. Vascular features may be more aggressive, with aortic aneurysms seen at an early age. Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies can help differentiate between Loeys-Dietz syndrome and MFS. Management is similar to MFS.
• Multiple endocrine neoplasia Multiple endocrine neoplasia Multiple endocrine neoplasia syndromes are autosomal dominant inherited conditions characterized by 2 or more hormone-producing tumors involving the endocrine organs. There are different types of MEN, namely MEN1-4. Multiple Endocrine Neoplasia, type 2B ( MEN 2B MEN 2b Similar to men2a, it is also caused by mutations of the men2 gene, also known as the ret proto-oncogene. Its clinical symptoms include medullary carcinoma of thyroid gland and pheochromocytoma of adrenal medulla (50%). Unlike men2a, men2b does not involve parathyroid neoplasms. It can be distinguished from men2a by its neural abnormalities such as mucosal neuromas on eyelids; lip; and tongue, and ganglioneuromatosis of gastrointestinal tract leading to megacolon. It is an autosomal dominant inherited disease. Multiple Endocrine Neoplasia): an autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance syndrome associated with medullary 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 carcinoma, pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma, oral mucosal neuromas Mucosal Neuromas Multiple Endocrine Neoplasia, and intestinal ganglioneuromas Intestinal Ganglioneuromas Multiple Endocrine Neoplasia. Affected individuals also have a marfanoid body habitus with skeletal abnormalities; however, the cardiovascular system and eyes are usually not affected. Genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies helps in diagnosis. Surgery is required to remove the neoplasms Neoplasms New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. Benign Bone Tumors. 
• Congenital Congenital Chorioretinitis contractural arachnodactyly: also known as Beals syndrome. An autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance condition affecting the fibrillin-2 protein. Affected individuals also have a marfanoid body habitus and cardiovascular manifestations. Flexion Flexion Examination of the Upper Limbs contractures Contractures Prolonged shortening of the muscle or other soft tissue around a joint, preventing movement of the joint. Wound Healing in many joints restrict movement. The 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 is not affected. The condition is diagnosed with clinical criteria and genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Management is based on the clinical manifestations.