Simpson-Golabi-Behmel Syndrome

A rare entity characterized by prenatal and postnatal overgrowth syndrome. Clinical features include abnormal sacrum, absent nails/claws, cleft palate most often associated with a cleft of the lower lip, coarse facial features, macroglossia, coloboma, congenital heart defects (ventricular septal defect, atrial septal defect), diaphragmatic hernia, hepatomegaly, fusion of cervical vertebra and limited extension, hydronephrosis, intestinal malrotation, kidney failure, macrocephaly, and increased risk of embryonal cancers.

Bulldog Syndrome; Simpson Dysmorphia Syndrome; X-Linked Dysplasia Gigantism Syndrome.

X-linked overgrowth syndrome in relation to the GPC3 coding region. Most families map Xq26; however, one large pedigree maps to Xp22.

Mutation in gene for glypican-3 (GPC3) located in the region of Xq26. GPC3 may modulate insulin-like growth factor 2 (IGF-2) in controlling embryonic mesodermal tissue to cause overgrowth syndrome.

The clinical manifestations include (according to the genetic origin): Xq26: coarse facies with mandibular overgrowth, cleft palate, congenital heart defects, hernias, supernumerary nipples, and renal and skeletal abnormalities; Xp22: lethal form, multiple organ anomalies, hydrops fetalis, and death within first 8 weeks of life. Radiological findings include flare of iliac wings, narrow sacroiliac notches, and advanced bone age in one series.

Wide spectrum of clinical manifestations from mild course with survival to adulthood to severe course with early neonatal death. Growth: increased birth weight and height; prenatal/ postnatal overgrowth; broad, stocky, “bulldog” appearance. Craniofacial: large head; coarse facies; hypertelorism; wide nasal bridge; upturned nasal tip; cup-shaped ears; large mouth; protruding jaw; enlarged tongue; cleft of lower lip; cleft palate. Eyes: cataract; retinal detachment. Trunk: short neck; pectus excavatum; accessory nipple; coccygeal skin tag and bony appendage. Cardiac: ventricular septal defect and pulmonary stenosis; arrhythmia may be common and is a possible cause of the high incidence of sudden death. Neurology: normal intelligence; clumsiness. Limbs: broad, short hands and fingers; postaxial polydactyly; syndactyly; simian crease. Gastroenterology: intestinal malrotation; Merkel diverticulum. Genitourinary: cryptorchidism; hypospadias. In one review, a similarity with Beckwith-Wiedemann syndrome was noted, and increased risk of neonatal hypoglycemia and embryonal tumor was suggested. High early perinatal and infant mortality was noted in another series.

Full history and examination must be obtained to delineate the clinical features present because of its wide spectrum. Assess cardiac function with examination, ECG, chest radiograph, Holter monitor, echocardiogram, and catheterization if indicated. Assess airway for potential difficulty.

Anesthetic technique should be tailored to the cardiac status and the procedure planned, including endocarditis prophylaxis, air embolism avoidance, and adequate rehydration. Arrhythmia is reported to be common and should be monitored for during the perioperative period. There is a significant potential for difficult airway maintenance during sedation or face-mask ventilation and possible difficult direct laryngoscopy and tracheal intubation in severe case of macroglossia. Blood sugar level should be monitored and intravenous dextrose may be required to avoid hypoglycemia.

The use of antibiotics for endocarditis prophylaxis must be considered.

Beckwith-Wiedemann Syndrome: Sporadic syndrome characterized by exomphalos, macroglossia, gigantism, and hypoglycemia as a consequence of hyperinsulinism.