Cornelia de Lange Syndrome and HDAC8 mutations

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I recently saw a female patient with a clinically apparent genetic mosaic abnormality, including patchy distribution of hyperpigmentation, organ hemi-hypertrophy, and dental and skeletal abnormalities. Testing for obvious genetic causes including CDPX and Incontinentia Pigmenti were non-informative.  We sent whole exome sequencing which revealed a novel, presumed loss of function mutation in HDAC8.

Loss-of-function mutations in HDAC8 were recently associated with X-linked Cornelia de Lange syndrome (Kaiser et al, Hum Mol Genet. 2014 Jun 1;23(11):2888-900. doi: 10.1093/hmg/ddu002). This is a diagnosis we would have never otherwise considered in this patient, and caused us to reason that mutations in HDAC8 should be considered in girls with a CDPX or IP like clinical presentation in whom genetic testing has been uninformative.

Hilary Vernon, MD PhD

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