Costello syndrome

Costello syndrome is a multiple congenital anomaly and mental retardation syndrome characterized by coarse face, loose skin, cardiomyopathy and predisposition to tumors.

Synopsis

 coarse face
 loose skin

 cardiovascular anomalies (63%) (12210337)

• cardiovascular malformation (CVM) (30%)
  • pulmonic stenosis (46% of CVM)

• cardiomyopathy (12210337) (12210337)
• myocardial hypertrophy (34%)
  • left ventricle (50%)
  • classic hypertrophic cardiomyopathy (HCM)

• rhythm disturbances (33%) (12210337)
  • atrial tachycardia (74%)

 tumoral predisposition (16010679)

• embryonal rhabdomyosarcoma (17164262, 16010679, 15167355, 11857556, 10664222, 9863604)
• neuroblastoma (16010679, 11131863, 11857556)
• bladder carcinoma (16010679, 11857556)
• schwannoma (11857556)

Etiology

 germline mutations in Costello syndrome (16170316)

• germline mutations in HRAS perturb human development and increase susceptibility to tumors.

References

 Schubbert S, Shannon K, Bollag G. Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 2007 Apr;7(4):295-308. PMID: 17384584

 Aoki Y, Niihori T, Kawame H, Kurosawa K, Ohashi H, Tanaka Y, Filocamo M, Kato K, Suzuki Y, Kure S, Matsubara Y. Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat Genet. 2005 Oct;37(10):1038-40. PMID: 16170316

 Gripp KW. Tumor predisposition in Costello syndrome. Am J Med Genet C Semin Med Genet. 2005 Aug 15;137(1):72-7. PMID: 16010679

 Hennekam RC. Costello syndrome: an overview. Am J Med Genet C Semin Med Genet. 2003 Feb 15;117(1):42-8. PMID: 12561057