Clefting

Gene: DNMT3B

Red List (low evidence)

Update from Clinical team. There are a large number of patients with the phenotype but insufficient evidence that clefting is a related feature. it is represented on more appropriate panels (It is a Green gene on the A- or hypo-gammaglobulinaemia v1.10 and Intellectual disability v1.151)

Created: 31 May 2017, 7:44 a.m.

Refer to clinical team for review for further discussion, unclear from the literature if there is enough evidence of clefting in ICF syndrome.

Created: 29 May 2017, 11:58 a.m.

Comment on publications:Hagleitner et al. (2008) reviewed the clinical features of 45 patients (39 families, with consanguinity confirmed in 18 patients) with Immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome). Facial dysmorphism, including epicanthic folds, hypertelorism, flat nasal bridge, and low-set ears, was commonly present. However 3 patients with a mutation in DNMT3B presented with cleft palate, but it is not clear form the paper if these three patients were related.
Weemaes et al. (2013). Among 44 patients (which included those reviewed by Hagleitner et al. 2008) with a clinical diagnosis of ICF, Weemaes et al. (2013) found that 23 (52%) had mutations in the DNMT3B gene and 13 (30%) had mutations in the ZBTB24 gene. Although the phenotype was noted as being relatively homogeneous, a few patients from both groups had congenital malformations including cardiac defects, cleft lip, clinodactyly, choanal stenosis, hip dislocation, and cerebral malformations. It was noted only one patient had Cleft lip.

Created: 29 May 2017, 11:52 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Immunodeficiency-centromeric instability-facial anomalies syndrome 1