Pulmonary Hypoplasia

Overview

Definition

Pulmonary hypoplasia is the insufficient or defective development of one or both 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, resulting in underdeveloped or undeveloped pulmonary parenchyma with decreased alveoli and airway branches.

• Classified as:
  • Type I (agenesis): complete absence of lung parenchyma, bronchus, and vessels
  • Type II (aplasia): the complete absence of pulmonary parenchyma with rudimentary bronchus
  • Type III (hypoplasia): some degree of pulmonary parenchymal development with decreased number of airways and alveoli
• Severity depends on the underlying cause and its timing in relation to fetal lung development.
• Can be unilateral or bilateral

Epidemiology

• Rare condition overall, with high rate of neonatal mortality and chronic morbidity for survivors
• Exact incidence is unknown but estimated to be 1.4 per 1000 births.
• Mortality and degree of morbidity related to gestational age when impacted:
  • Often lethal
  • Mortality rate of 47% in the 1st 60 days of life in affected babies born alive
  • Mild to severe respiratory symptoms for children who survive the immediate neonatal period
  • Can be a cause of more mild and chronic respiratory symptoms, sometimes discovered later, even into adulthood

Etiology

• Impairment of lung development, especially before 22 weeks of gestational age
• Causes involve multiple factors: 
  • Genetic
  • Environmental
  • Maternal
  • Nutritional
• Primary hypoplasia:
  • Rare and fatal (e.g., congenital acinar dysplasia)
  • Not well understood but are thought to be genetic 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 growth and transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription factors, which are key to lung development
• Secondary hypoplasia:
  • Majority of cases
  • Due to other fetal developmental abnormalities
  • Conditions that lead to reduced space of the thoracic cavity during fetal development:
    • Congenital diaphragmatic hernia (CDH)
    • Fetal hydrops ( pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion)
    • Mediastinal mass
    • Congenital cystic adenomatoid malformations or CCAM (now referred to as congenital pulmonary airway malformation (CPAM))
    • Abdominal tumors
    • Skeletal abnormalities (thoracic dystrophy or Jeune syndrome, skeletal dysplasia, chest wall Chest wall The chest wall consists of skin, fat, muscles, bones, and cartilage. The bony structure of the chest wall is composed of the ribs, sternum, and thoracic vertebrae. The chest wall serves as armor for the vital intrathoracic organs and provides the stability necessary for the movement of the shoulders and arms. Chest Wall tumors)
  • Conditions associated with oligohydramnios before 28th week of gestation:
    • Renal agenesis
    • Urinary outflow tract obstructive lesions
    • Prolonged, preterm membrane rupture
    • Bilateral cystic kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys
  • Disorders of impaired breathing:
    • Phrenic nerve abnormality
    • Neuromuscular or CNS disorders
  • Chromosomal abnormalities:
    • Trisomy 21 ( Down syndrome Down syndrome Down syndrome, or trisomy 21, is the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Both boys and girls are affected and have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, gastrointestinal, ocular, and auditory systems. Down Syndrome)
    • Trisomy 13 Trisomy 13 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) ( 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))
    • Trisomy 18 Trisomy 18 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) (Edwards’ syndrome)
  • Congenital heart disease with pulmonary blood flow impairment:
    • 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
    • Pulmonary artery hypoplasia
    • Hypoplastic right heart

Pathophysiology

Fetal lung development

• 4th week of gestation:
  • Laryngotracheal groove forms from the wall of the primitive pharynx Pharynx The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx → the groove elongates, with distal end bifurcating into tracheal buds and then bronchial buds
  • Process of elongation and branching of buds continues as conducting airways up to 16 weeks of gestation.
• From 16 weeks to birth, the gaseous exchange system (acini) develops:
  • 16–26 weeks: canalicular stage
  • 26–40 weeks: terminal sac stage
• Normal development of the fetal lung depends on: 
  • Normal thoracic cavity space
  • Mechanical forces that require adequate amniotic fluid:
    • Spontaneous contraction of developing airways
    • Fetal breathing movements

Abnormal fetal lung development

Multiple aspects of the impairment of fetal lung growth can lead to hypoplasia.

• Oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios:
  • Lack of amniotic fluid → lack of lung distensibility and arterial branching → decreased surface area for gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange
  • Can be secondary to:
    • Premature rupture of membranes at early gestational age
    • Renal dysgenesis or agenesis (at 16 weeks of gestational age, fetal urine becomes the main source of amniotic fluid)
  • Potter sequence, or Potter syndrome (historic term), encompasses features resulting from oligohydramnios and causing mechanical compression: 
    • Pulmonary hypoplasia
    • Limb deformities
    • Potter facies (flattened nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose, recessed chin, epicanthal folds, low-set ears)
• Reduced thoracic space:
  • Intrathoracic lesions:
    • CPAM
    • Pleural effusion
  • Extrathoracic lesions:
    • CDH
    • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
    • Eventration of diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm 
• Impairment in fetal breathing, which is important for lung maturation:
  • Neuromuscular:
    • Spinal muscular atrophy Spinal Muscular Atrophy Spinal muscular atrophy (SMA) is a spectrum of autosomal recessive syndromes characterized by progressive proximal muscle weakness and atrophy, possibly due to degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem. Spinal Muscular Atrophy (SMA)
    • Congenital myotonic dystrophy
  • Restrictive:
    • Congenital thoracic dystrophy
    • Short rib polydactyly syndrome
  • Brain stem Brain Stem The brain stem is a stalk-like structure that connects the cerebrum with the spinal cord and consists of the midbrain, pons, and medulla oblongata. It also plays a critical role in the control of cardiovascular and respiratory function, consciousness, and the sleep-wake cycle. Brain Stem impairment of normal breathing patterns

Clinical Presentation

Antenatal

• Decreased fetal movement during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
• Oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios
• Ultrasound detection of anatomic malformations or masses
• Ultrasound detection of other congenital abnormalities
• Prenatal diagnosis of associated chromosomal abnormalities 

Postnatal

• Often lethal
• Babies who survive the immediate neonatal period may have:
  • Mild to severe respiratory distress
  • Bell-shaped thoracic cavity in bilateral pulmonary hypoplasia
  • Asymmetrical ventilation and decreased ventilation on the affected side, if unilateral
  • Imaging showing:
    • Space-occupying lesion such as CPAM
    • Interthoracic abdominal contents on the affected side
  • Bronchopulmonary dysplasia
  • Alveolar hemorrhage
  • 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
  • Renal mass or enlarged bladder
  • Classic Potter syndrome features:
    • Potter facies
    • Pulmonary hypoplasia
    • Limb deformities
• If mild at birth, later development of:
  • Recurrent pulmonary infections
  • Exercise intolerance

Complications

• Immediate neonatal period:
  • Acute respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
  • 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
  • Tracheomalacia Tracheomalacia Laryngomalacia and tracheomalacia are the most common upper airway conditions that produce stridor in newborns. Laryngomalacia and tracheomalacia tend to present in the 1st 2 weeks of life, with symptoms ranging from stridor to respiratory distress. The symptoms are caused by narrowing of the airway, which may be due to weakened cartilage, redundant tissue, external compression, or hypotonia of the affected area. Laryngomalacia and Tracheomalacia
  • Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension
• Long term:
  • Chronic lung disease
  • Respiratory infections
  • Limited exercise capacity
  • Poor growth
  • 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

Mnemonic for Potter sequence

• P: pulmonary hypoplasia (leads to respiratory insufficiency)
• O: oligohydramnios (can be the cause or an associated finding)
• T: twisted face (e.g., beaked nose Nose The nose is the human body's primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Anatomy of the Nose, low-set ears, prominent epicanthal folds)
• T: twisted 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. Structure and Function of the Skin
• E: extremity defects (limb malformations)
• R: renal failure (in utero)

Diagnosis

Antenatal

• Fetal ultrasonography to look for:
  • Oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios
  • Decreased fetal movement
  • Growth restriction or anatomic abnormalities
  • Hydrops
  • Intrathoracic masses
  • Ratio of thoracic circumference to abdominal circumference: < 0.6
  • Lung weight:body weight (LW:BW) ratio: 
    • 0.015 if < 28 weeks
    • 0.012 if > 28 weeks
  • Radial alveolar count:
    • Defined as number of alveoli that cross a line drawn from a respiratory bronchiole to the nearest 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 septum
    • < 75% of the standard value
• MRI:
  • Abnormal anatomy
  • Volumetric assessment 
• Chromosomal analysis showing abnormalities associated with pulmonary hypoplasia: 
  • Trisomy 21 ( Down syndrome Down syndrome Down syndrome, or trisomy 21, is the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Both boys and girls are affected and have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, gastrointestinal, ocular, and auditory systems. Down Syndrome)
  • Trisomy 13 Trisomy 13 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) ( 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))
  • Trisomy 18 Trisomy 18 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) (Edwards’ syndrome)

Postnatal

• Initial physical exam:
  • Check level of respiratory distress.
  • Scaphoid abdomen seen with CDH
  • Decreased or absent lung sounds on the affected side
  • Potter syndrome features (flattened facies, limb malformations)
  • Other physical findings typical for other underlying chromosomal abnormalities:
    • Trisomy 21: hypotonia, murmur, epicanthal folds, simian crease
    • Trisomy 13 Trisomy 13 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): 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 and/or 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. Oral Cavity: Palate, hypotonia, microphthalmia
    • Trisomy 18 Trisomy 18 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): microcephaly, clenched fists, convex sole of foot (rocker bottom)
    • 22q deletion: craniosynostosis Craniosynostosis Craniosynostosis is the premature fusion of 1 or more cranial sutures during the 1st year of life. Craniosynostosis is classified as simple or complex, and can be caused by environmental factors or genetic syndromes. Craniosynostosis, polydactyly
• Chest X-ray:
  • Bilateral pulmonary hypoplasia is shown by bell-shaped chest and elevation of the diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm.
  • Unilateral pulmonary hypoplasia shows:
    • Opaque hemithorax
    • Rib crowding
    • Ipsilateral mediastinal shift
    • Hyperinflated contralateral lung in unilateral pulmonary hypoplasia
• CT: to confirm hypoplasia and rule out other causes of respiratory distress
• Electrocardiography
• Chromosomal analysis in some cases, and counseling for parents
• Pulmonary function tests for older children and adults

Management

Antenatal

• Steroids to help with fetal lung maturation in fetuses 24–34 weeks of gestational age
• Tocolytics and antibiotics in the case of premature rupture of membranes
• Amnio-infusion and amniopatch can be attempted.
• Fetal endoscopic tracheal occlusion may improve outcomes for CDH (under investigation):
  • Occlusion blocks the airway, allowing fluid buildup and lung growth.
  • Pulmonary artery hypertension and pulmonary hypoplasia can be minimized.
  • Occlusion (tracheal balloon) is removed before birth and timed to allow for type 2 pneumocyte development and adequate surfactant production.

Postnatal

• Immediate respiratory support as needed; may include:
  • Supplemental oxygen
  • Surfactant administration
  • Endotracheal intubation and mechanical ventilation
  • ECMO
• Inhaled NO for pulmonary hypertension
• Surgical correction in cases of CDH and other congenital defects
• Address other complications (e.g., cardiac, gastrointestinal)

Prognosis

• Primary pulmonary hypoplasia is rare and usually lethal.
• Overall prognosis depends on: 
  • Underlying cause
  • Associated conditions
  • Degree of hypoplasia
• Poor prognostic factors:
  • CDH has a 50% mortality rate, with worse prognosis in:
    • Right-sided lesion
    • Associated pulmonary hypertension
  • Presence of genetic abnormalities
  • Severe oligohydramnios for > 2 weeks
  • Rupture of membranes, especially at < 25 weeks of gestation
• Other factors to consider:
  • Infants with unilateral pulmonary hypoplasia can do well if there are no associated lesions or genetic anomalies.
  • Some infants delivered many weeks after premature rupture of membranes can have good outcomes, with improved lung function over time.
  • Pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension may resolve with good support and management.
• Survivors may have:
  • Chronic lung disease
  • Limited exercise tolerance
  • Increased risk of pulmonary infection

Clinical Relevance

• Congenital diaphragmatic hernia: a congenital defect in the fetal diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm that allows herniation of abdominal contents into the thorax, leading to pulmonary hypoplasia on the affected side: The types of hernia are posterolateral Bochdalek (left-sided Bochdalek in 85% of cases), anterior Morgagni, paraesophageal, and hiatal. Mild cases can be repaired in the first days of life with a good long-term prognosis. More severe cases require high levels of support, with long-term respiratory, neurodevelopmental, and growth issues and can be lethal.
• Congenital pulmonary airway malformation (CPAM): previously known as congenital cystic adenomatoid malformation (CCAM): Rare hamartomatous cystic and adenomatous lesions in the lung can occur in either side of the lung (unilobar or multilobar). If large enough, these lesions can lead to pulmonary hypoplasia and hydrops. Affected children can be asymptomatic at birth or can present with infections. Other risks include spontaneous pneumothorax and, rarely, malignancy. Management may involve resection before 1 year of age or close observation, depending on the size and other risk factors.
• Oligohydramnios Oligohydramnios Oligohydramnios refers to amniotic fluid volume less than expected for the current gestational age. Oligohydramnios is diagnosed by ultrasound and defined as an amniotic fluid index (AFI) of ‰¤ 5 cm or a single deep pocket (SDP) of < 2 cm in the 2nd or 3rd trimester. Oligohydramnios: amniotic fluid volume reduced for gestational age: Diagnosis is by ultrasonography: amniotic fluid index of ≤ 5 cm. The different etiologies include maternal (e.g., medications, preeclampsia), placental (e.g., abruption), fetal (e.g., chromosomal abnormalities), and/or idiopathic. First-trimester oligohydramnios carries a poor prognosis. For subsequent trimesters, a fetal structural survey is performed, determining fetal abnormalities, along with serial ultrasound monitoring. Short-term improvement can be achieved with amnio-infusion.
• Trisomy 21, or Down syndrome Down syndrome Down syndrome, or trisomy 21, is the most common chromosomal aberration and the most frequent genetic cause of developmental delay. Both boys and girls are affected and have characteristic craniofacial and musculoskeletal features, as well as multiple medical anomalies involving the cardiac, gastrointestinal, ocular, and auditory systems. Down Syndrome: a genetic syndrome caused by the presence of an extra chromosome 21; associated with advanced maternal age: This syndrome may be suspected on fetal ultrasonography and on prenatal screening (typically low alpha-fetoprotein, estriol) and confirmed with genetic testing. Classic features include hypotonia, short neck, epicanthal folds, cardiac defects, and simian crease. There is an increased incidence of pulmonary hypoplasia.
• Trisomy 18 Trisomy 18 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) (Edwards’ syndrome): the 2nd most common trisomy. This genetic syndrome is caused by the presence of 3 copies of chromosome 18, with predominance in girls. Characteristic features include intrauterine growth restriction, cardiac defects, clenched fists with overlapping fingers, and rocker bottom feet. Other findings can include diaphragmatic eventration and lung hypoplasia. Diagnosis is made by karyotype analysis. No treatment is available, and many patients do not survive beyond 1 year of life.
• Trisomy 13 Trisomy 13 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) ( 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)): the 3rd most common trisomy: This genetic syndrome is caused by the presence of 3 copies of the 13th chromosome. Clinical features include brain 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 malformations, cardiac 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. Oral Cavity: Palate, and hypotonia. This syndrome is also associated with pulmonary hypoplasia. Diagnosis is made by karyotype analysis. No treatment is available, and most patients do not survive beyond 1 year of life.