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Tuberous Sclerosis

Introduction Tuberous sclerosis, also known as the tuberous sclerosis complex (TSC), is a disorder of cellular differentiation, proliferation, and migration in early development that variably affects multiple organ systems. First described in 1862 by Friedrich von Recklinghausen, TSC is characterized by the formation of benign, hamartomatous lesions in virtually any organ system, most commonly the central nervous system (CNS), skin, heart, lungs, kidneys, bones, and blood…

Pontocerebellar Disorders

Introduction Autosomal recessive pontocerebellar hypoplasias (PCHs) are a group of severe neurodegenerative disorders affecting the cerebellum and pons. This disease appears in fetal or neonatal life with subsequent pontocerebellar degeneration, progressive microcephaly, and atrophy of the cerebral cortex. Most affected individuals have profound motor and cognitive deficits. Life expectancy generally lasts into infancy or childhood, though there are reports of some individuals with PCH who live…

Cystic Fibrosis

Introduction Cystic fibrosis (CF) is a single-gene autosomal recessive disorder characterized by chronic airway infection, pancreatic insufficiency, gastrointestinal dysfunction, and male infertility. Symptoms typically manifest during childhood, leading to early mortality in the third and fourth decades of life. Greater than 1000 different mutations in the CF transmembrane conductance regulator (CFTR) gene have been identified with an expansive ethnic and racial distribution as well as varying…

Roberts Syndrome

Introduction Roberts syndrome, also known as Roberts-SC phocomelia syndrome or pseudothalidomide syndrome, is a rare genetic disorder characterized by prenatal growth restriction, limb reductions, and craniofacial abnormalities. The upper extremities are more severely affected than the lower extremities, with common limb abnormalities including bilateral symmetric tetraphocomelia or hypomelia. Other limb malformations, such as oligodactyly, syndactyly ( Fig. 140.1 ), clinodactyly, and elbow and knee flexion contractures,…

Prune-Belly Syndrome

Introduction Prune-belly syndrome (PBS), also known as Eagle-Barrett syndrome, is a triad of anomalies composed of abdominal wall flaccidity, urologic abnormalities, and bilateral cryptorchidism. The typical urologic findings are distended bladder, hydronephrosis, and renal dysplasia. A patent urachus is a common finding. In some infants, urinary obstruction may lead to oligohydramnios or anhydramnios with a resulting Potter sequence (pulmonary hypoplasia, dysmorphic facies). Concomitant cardiac, orthopedic, and…

Poland Sequence

Introduction Poland sequence refers to congenital unilateral absence of the sternal costal portion of the pectoralis major muscle and ipsilateral upper limb anomalies. There is no known genetic etiology for Poland sequence. The pathogenesis of this disorder is suggested to be caused by a vascular disruptive sequence. Postpartum management usually consists of surgical correction and rehabilitation therapy for musculoskeletal defects. Disease Definition There are no formal…

Pierre Robin Sequence

Introduction Pierre Robin sequence (PRS) is a result of hypoplasia of the mandible leading to retrognathia or micrognathia, cleft palate, and posterior displacement of the tongue (glossoptosis). The classic cleft palate in PRS is a U-shape. Retrognathia and glossoptosis lead to airway obstruction of varying severity, occasionally requiring intubation or tracheostomy for airway management. The PRS may occur in isolation or as part of a syndrome.…

Pentalogy of Cantrell

Introduction First described in 1958, pentalogy of Cantrell is a rare syndrome consisting of five anomalies including: (1) a midline supraumbilical abdominal wall defect, (2) a defect in the diaphragmatic pericardium, (3) a defect in the lower sternum, (4) a defect in the anterior diaphragm, and (5) various intracardiac anomalies. In the most severe cases, the heart herniates through the diaphragmatic defect, resulting in ectopia cordis.…

Noonan Syndrome

Introduction Noonan syndrome (NS), first described by Dr. Jacqueline Noonan in 1968, is a disorder characterized by facial dysmorphisms, cardiovascular defects primarily consisting of pulmonary stenosis, short stature, and variable developmental delay. In addition, affected individuals often display pectus excavatum or carinatum, webbed neck, coagulopathies, and ocular anomalies. There is a great deal of variability in disease expression. NS is genetically heterogeneous; in almost all cases,…

Neu-Laxova Syndrome

Introduction Neu-Laxova syndrome (NLS) is an autosomal recessive, lethal disorder. The syndrome was first described in 1971 by Neu et al. who reported three siblings who were either stillborn or died shortly after birth with microcephaly and multiple congenital anomalies. In 1972 Laxova et al. reported three siblings born to consanguineous parents with similar findings. In 1979 Lazjuk et al. described another case with similar findings and named the…

Meckel-Gruber Syndrome

Introduction Meckel-Gruber syndrome, also known as Meckel syndrome or Gruber syndrome, is a severe ciliopathy. This developmental disorder was first described by Meckel in 1822 and later by Gruber in 1934. The minimum diagnostic criteria are controversial because the clinical manifestations of the syndrome are highly variable. The classic triad consists of a central nervous system malformation, typically occipital encephalocele; cystic kidneys; and polydactyly, most commonly…

Holt-Oram Syndrome

Introduction Holt-Oram, also known as hand-heart syndrome I, was first described in 1960 by Mary Clayton Holt and Samuel Oram as a constellation of malformations that they observed in four generations of one family. The original description included atrial septal defects and a thumb anomaly that lay in the same plane as the finger. Individuals affected by this disorder have the classically described upper limb anomaly…

Klippel-Trénaunay-Weber Syndrome

Introduction Klippel-Trénaunay-Weber syndrome (KTWS) is characterized by a triad of cutaneous hemangiomas, hemihypertrophy, and vascular abnormalities. This triad of anomalies was first described by Klippel and Trénaunay in 1900. Parkes-Weber described an additional case 18 years later that had the triad of findings described by Klippel and Trénaunay and an arteriovenous malformation. The exact pathophysiology and genetic etiology of the disorder are unknown. Treatment consists of…

Goldenhar Syndrome

Introduction In 1952, Dr. Maurice Goldenhar described a variant of hemifacial microsomia. Although Goldenhar syndrome is frequently listed as synonymous with hemifacial microsomia, it is distinct. Also known as ocular-auriculo-vertebral syndrome, Goldenhar syndrome is a defect in the development of the first and second branchial arches. Characterized by epibulbar dermoids, mandibular asymmetry, and cervical vertebrae anomalies, the syndrome exhibits extreme heterogeneity. Disorder Definition The heterogeneous nature…

Fryns Syndrome

Introduction First described in 1979, Fryns syndrome is a rare autosomal recessive disorder characterized by diaphragmatic defects, dysmorphic facial features, distal limb hypoplasia, pulmonary hypoplasia, and associated anomalies of other major organ systems. To date the diagnosis is made solely by clinical criteria, as only one candidate gene has been identified through whole exome sequencing. Although Fryns syndrome was initially thought to be uniformly lethal, there…

Fraser Syndrome

Introduction Fraser syndrome is a rare congenital malformation syndrome characterized by cryptophthalmos, syndactyly, and urogenital defects. Disease Definition Thomas et al. formulated the diagnostic criteria for Fraser syndrome including four major (cryptophthalmos, syndactyly, abnormal genitalia, and affected sibling) and eight minor criteria (congenital malformations of nose, ears, and larynx; cleft lip with or without cleft palate; skeletal symptoms; umbilical hernia; renal agenesis; mental retardation). These authors suggested…

Cornelia de Lange Syndrome

Introduction Cornelia de Lange syndrome (CdLS), also known as Brachmann-de Lange or de Lange syndrome, is a condition characterized by mental retardation, craniofacial dysmorphism, prenatal and postnatal growth failure, hirsutism, and upper limb abnormalities. Other defects occasionally associated with CdLS include congenital cardiac defects and genital anomalies. There are three subtypes of CdLS. CdLS1, the classic form, is caused by autosomal dominant mutations in the NIPBL…

CHARGE Syndrome

Introduction CHARGE ( c oloboma, h eart disease, choanal a tresia, r etardation, g enital hypoplasia, and e ar anomalies) syndrome is an autosomal dominant disorder that was first described as a recognizable pattern of congenital malformations by Hall in 1979. He described 17 children with multiple congenital anomalies in which choanal atresia was the primary feature. Also in 1979, Hittner et al. described 10 children with…

Fetal Biophysical Profile

Introduction The biophysical profile (BPP) was first described in 1980 as a method to quantify and standardize antepartum fetal evaluation. The full BPP test is performed using a combination of real-time ultrasound (US) and cardiotocography, also known as a nonstress test (NST). The US component combines the assessment of four activities: fetal movement, fetal breathing, and tone over a 30-minute period, along with amniotic fluid assessment.…

Cervical Length and Spontaneous Preterm Birth

Introduction Preterm birth (PTB) touches communities everywhere. Around the world, one in 10 babies is born too early. The toll is more than 15,000,000 babies per year. The deep impact of this problem has fostered widespread efforts to use the best available medical practices to address it. Accordingly, the U.S. PTB rate fell from 10.44% to 9.57% from 2007–2014, although, unfortunately, preliminary 2015 birth data shows…