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Pitt-Hopkins syndrome

The Pitt-Hopkins syndrome (PTHS) is characterized by mental retardation, wide mouth and distinctive facial features, and intermittent hyperventilation followed by apnea.

Synopsis

- mental retardation
- wide mouth
- intermittent hyperventilation
- hyperventilation
- Hirschsprung disease

Differential diagnosis

- Angelman syndrome
- Rett syndrome

Etiology

- haploinsufficiency of TCF4

  • Both null and missense mutations impaired the interaction of TCF4 with ASCL1 from the PHOX-RET pathway in transactivating an E box-containing reporter construct.

References

- Zweier C, Peippo MM, Hoyer J, Sousa S, Bottani A, Clayton-Smith J, Reardon W, Saraiva J, Cabral A, Gohring I, Devriendt K, de Ravel T, Bijlsma EK, Hennekam RC, Orrico A, Cohen M, Dreweke A, Reis A, Nurnberg P, Rauch A. Haploinsufficiency of TCF4 Causes Syndromal Mental Retardation with Intermittent Hyperventilation (Pitt-Hopkins Syndrome). Am J Hum Genet. 2007 May;80(5):994-1001. PMID: 17436255

- Amiel, J.; Rio, M.; de Pontual, L.; Redon, R.; Malan, V.; Boddaert, N.; Plouin, P.; Carter, N. P.; Lyonnet, S.; Munnich, A.; Colleaux, L. : Mutations in TCF4, encoding a class I basic helix-loop-helix transcription factor, are responsible for Pitt-Hopkins syndrome, a severe epileptic encephalopathy associated with autonomic dysfunction. Am. J. Hum. Genet. 80: 988-993, 2007. PubMed ID : 17436254