Intellectual disability update Jan 2018

Gene: NHP2

Comment on publications: added publications to support the association to the disorder

Created: 23 Feb 2018, 5:11 p.m.

Comment on list classification: Associated with phenotype in OMIM and as a probable G2P. Biallelic variants of the gene NHP2 are known to cause Dyskeratosis congenital (DC) and have been reported in two families to date, of which only one one case has been reported with intellectual disability. There is potentially a third case for Dyskeratosis congenital PMID: 25907943 but there is no mention of intellectual disability phenotype.
From Savage et al, 2009 PMID:20301779 patients with DC are at increased risk for progressive bone marrow failure (BMF), myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML), solid tumors (usually squamous cell carcinoma of the head/neck or anogenital cancer), and pulmonary fibrosis. Other findings can include: abnormal pigmentation changes not restricted to the upper chest and neck, eye abnormalities (epiphora, blepharitis, sparse eyelashes, ectropion, entropion, trichiasis), and dental abnormalities (caries, periodontal disease, taurodauntism). Although most persons with DC have normal psychomotor development and normal neurologic function, significant developmental delay is present in the two variants in which additional findings include cerebellar hypoplasia (Hoyeraal Hreidarsson syndrome) and bilateral exudative retinopathy and intracranial calcifications (Revesz syndrome), of which the gene NHP2 is not involved.

Created: 23 Feb 2018, 5:04 p.m.