Overgrowth disorders Flashcards
BECKWITH-WIEDEMANN SYNDROME
Responsible genes:
Proteins:
Cytogenetic locus:
Inheritance:
Clinical Features and Diagnostic Criteria:
Clinical Tests:
Molecular Tests:
Disease Mechanism:
Treatment/Prognosis:
Responsible genes: CDKN1C, H19, KCNQ1OT1
Proteins: cyclin-dep kinase inhib 1C, H19 maternally expressed untranslated mRNA, potassium
voltage-gated channel, KQT-like subfamily, member 1
Cytogenetic locus: 11p15.5
Inheritance: AD (15%)
Clinical Features and Diagnostic Criteria: hemihyperplasia, macrosomia, macroglossia,
visceromegaly, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma,
rhabdomyosarcoma), omphalocele, neonatal hypoglycemia, ear creases/pits, adrenocortical
cytomegaly, and renal abnormalities
Clinical Tests: AFP, abdominal CT
Molecular Tests: Cytogenetically detectable abnormalities of 11p15 (<1%); loss of methylation at
DMR2 (50%); gain of methylation at DMR1 (2% -7%); pat. UPD for 11p15 (10-20%); mutations in the
CDKN1C (40% of familial cases and 5-10% of sporadic cases)
Disease Mechanism: imprinted genes including growth factors and tumor suppressor genes in the
11p15.5 region
Treatment/Prognosis: 20% mortality, Screening for embryonal tumors: abdominal US every three
months until eight years. Serum AFP concentration is monitored in the first few yrs of life for
hepatoblastoma.
SOTOS SYNDROME
Responsible gene:
Protein:
Cytogenetic locus:
Inheritance:
Clinical Features and Diagnostic Criteria:
Clinical Tests:
Molecular Tests:
Disease Mechanism:
Treatment/Prognosis:
Responsible gene: NSD1
Protein: Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific
Cytogenetic locus: 5q35 Inheritance: AD
Clinical Features and Diagnostic Criteria: classic: macrocephaly, pointed chin, tall stature
and increased body mass, delayed motor skills, delayed cognitive, verbal, and social
development, advanced BA. Less common: phobias, aggression, OCD, ADD, abnormal EEG
and seizure, chronic OM and constipation, congenital heart defects, strabismus,
hyper/hypothyroidism, possible inc risk of tumors (saccrococcygeal teratoma and
neuroblastoma).
Clinical Tests: Bone age. Brain MRI or CT may show inc ventricles
Molecular Tests: MLPA or FISH for 5q35 microdeletion including NSD1: ~15% (70% in
Japanese). NSD1 sequencing: 27-93% (12% in Japanese)
Disease Mechanism: Haploinsufficiency of NSD1. May be related to genes affecting growth.
Treatment/Prognosis: Supportive treatment, most end up of ave adult Ht, IQ ranges from
normal to ID. Cancer screening is not rec. (risk ~1%)
