Simpson-Golabi-Behmel Syndrome

At a glance

A rare X-linked recessive 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.

Synonyms

Bulldog Syndrome; Simpson Dysmorphia Syndrome; X-Linked Dysplasia Gigantism Syndrome; Simpson-Golabi-Behmel Syndrome Type 1; SGBS; Mental Retardation-Overgrowth Syndrome.

Incidence

More than 250 patients have been described worldwide.

Genetic inheritance

X-linked recessive.

Pathophysiology

Overgrowth syndrome in relation to the GPC3 coding region. Most families map Xq26 (Type 1); however, one large pedigree maps to Xp22 (Type 2). 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.

Diagnosis

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. Prenatal diagnosis possible after 20 weeks.

Clinical aspects

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; largemouth; 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 possible; 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.

Precautions before anesthesia

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 considerations

Anesthetic technique should be tailored to the cardiac status and ...