Beckwith-Wiedemann syndrome
Epidemiology and Etiology:
- 85% sporadic
- Methylation abnormality (most)
- Methylation of both copies of H19
- hypomethylation of both copies of KCNQOT1
- loss of expression of (maternal) CDKN1C
- upd(11)pat
(10-20%)
- partial paternal UPD for distal 11p
- only a single case of mosaic full
paternal UPD11 (usually
associated with severe IUGR
- isodisomic and usually confined to the 11p15 regionn
(not whole chromosome UPD)
- post-fertilization error
- somatic recombination
- gene conversion
- familial:
- distal 11p aberrations (some)
- biallelic
expression of the paternally expressed insulin-like growth factor II
(IGF2) (some patients without the above abnormalities)
- CDKN1C gene mutations on maternal allele(5-10%
of sporadic) (40% of AD BWS)
Common sites:
- GU:
- Adrenal:
- Adrenal cortical neoplasia
- Liver:
- Pancreas:
- Soft tissue:
Gross features:
- Large for gestational age
- Organomegaly
- Hepatomegaly
- nephromegaly
- macroglossia
- hemihypertrophy
- anterior abdominal wall defects
- posterior helical indentations
- GU abnormalities
Histologic features:
- adrenal cortex cytomegaly
Immunophenotype:
Marker:
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Sensitivity:
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Specificity:
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Molecular features:
- KCNQOT1 (?KVDMR)
- Transcribed but not translated
- Imprinted (paternal allele expressed)
- CDKN1C
- Protein-encoding
- CDK inhibitor 1C (p57KIP2)
- Cell cycle suppressor
- Maternal allele expressed
- Inhibited by KCNQOT1 expression (iso)
- H19
- Imprinted
- Transcribed but not translated
- Imprinted (maternal allele expressed)
- IGF2
- Protein-encoding
- Insulin-like growth factor
- Promotes growth
- Paternal allele expessed
- Inhibited by H19 (iso)
Other features:
- mental retardation – may be secondary to
hypoglycemia
- neonatal onset hypoglycemia
- clinical features:
- overgrowth syndrome
- macroglossia
- organomegaly
- omphalocele
- neonatal hypoglycemia
- other malformations
- risk for tumours:
References:
- ACMG Statement on Diagnostic Testing for Uniparental Disomy (2001)
- Nussbaum RL, McInnes
RR, Willard HF. Thompson & Thompson Genetics in Medicine: With
STUDENT CONSULT Online Access. 7th ed. Saunders; 2007.