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
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
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
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.