BECKWITH-WIEDEMANN SYNDROME
DEFINITION:
A syndrome characterized by neonatal hypoglycemia and dysmorphic
features including macroglossia, macrosomia, visceromegaly,
omphalocele, and distinctive ear anomalies.
EPIDEMIOLOGY:
- incidence: ?
- age of onset:
- risk factors:
- familial - sporadic mutation (in 85% of cases)
- chrom.#: 11pter-p15.4
- gene: ?
- M = F
PATHOGENESIS:
- etiology unknown
- neonatal abnormalities such as prematurity, polyhydramnios,
dysmorphic features, macrosomia suggest a prenatal etiology -
excessive growth rate often slows down after the first few years
2. Genetic Defect
- the gene for insulin-like growth factor II is found within
the 11pter-p15.4 region and may be responsible for:
- pancreatic islet hyperplasia (nesidioblastosis)
- relative hyperinsulinemia -> neonatal hypo-glycemia
- microcephaly and retarded brain development may occur
independent of hypoglycemia
2. Visceromegaly
- nephromegaly, hepatomegaly, and splenomegaly during
embryogenesis may predispose to certain developmental
defects -> anomalies of intestinal rotation and fixation,
omphalocele, diaphragmatic eventration, renal medullary
dysplasia
3. Gonads
- gonadal interstitial cell hyperplasia (in males)
4. Pituitary
2. Neoplastic Transformation
- in 5% - adrenocortical carcinoma, Wilms' tumor
- rare - carcinoid tumor, embryonal rhabdomyosarcoma,
fibroma, glioma, gonadoblastoma, hepato-blastoma, myxoma,
retinoblastoma
- Note: the genes for rhabdomyosarcoma, adrenocortical
carcinoma and Wilms' tumor are also on chromosome 11
CLINICAL FEATURES:
- dysmorphic features (see below) and neonatal somatic
gigantism
- apnea, cyanosis, seizures, feeding difficulties due to
macro-glossia
- hypoglycemia
- tends to be intractable, severe, and persist for months
2. Clinical Features
-
Feature(%)
- macroglossia (98%)
- nephromegaly (97%)
- splenomegaly (82%)
- midface hypoplasia (81%)
- cryptorchidism (81%)
- omphalocele (76%)
- hepatomegaly (73%)
- prominent occiput (72%)
- ear anomalies - creases, pits (66%)
- facial nevusflammeus (62%)
- neonatal hypoglycemia (61%)
- polyhydramios (51%)
- umbilical hernia (49%)
- cardiac defects (34%)
- hemihypertrophy (33%)
- diastasis recti (33%)
- others: MR,microcephaly, tall stature
3. Complications
- neoplastic transformation (see above)
INVESTIGATIONS:
- neonatal polycythemia
- hypoglycemia with hyperinsulinemia
- moniter alpha fetoprotein and abdominal U/S q6m till age 6
years to screen for hepatoblastoma and Wilms tumor, respectively
2. Imaging Studies
MANAGEMENT:
- Paediatrics, Surgery, Speech Therapy
- feeding difficulties - use large, soft nipple
- upper airway obstruction - place on side and stomach
- stabilization of omphalocele
2. Hypoglycemia
- steroids for 1-4 months
- glucose infusions
- see file on "Hypoglycemia"
2. Surgery
- omphalocele repair
- orthognathic and orthodontic
- ? role of partial glossectomy
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