Long term follow‐up in a patient with a de novo microdeletion of 14q11.2 involving CHD8

Abstract

We identified a de novo deletion of 14q11.2 in a Czech patient with developmental delay, mild autistic features, macrosomy, macrocephaly, orthognathic deformities, and dysmorphic facial features. The clinical follow-up of the patient lasting 14 years documented changes in the facial dysmorphism from infancy to adolescence. The deletion affects approximately 200 kb of DNA with five protein-coding genes and two snoRNA genes. Two of the protein-coding genes, SUPT16H and CHD8, have been proposed as candidate genes for a new microdeletion syndrome. Our patient further supports the existence of this syndrome and extends its phenotypic spectrum, especially points to the possibility that orthognathic deformities may be associated with microdeletions of 14q11.2. CHD8 mutations have been found in patients with neurodevelopmental disorders and macrocephaly. The HNRNPC gene, repeatedly deleted in patients with developmental delay, is another candidate as its 5́ end is adjacent to the deletion, and the expression of this gene may be affected by position effect.

A spontaneous missense mutation in the chromodomain helicase DNA‐binding protein 8 (CHD8) gene: a novel association with congenital myasthenic syndrome

“…Myasthenia has to date not been reported in association with CHD8 mutations. The clinical phenotype of patients with CHD8 mutations does vary, but macrosomia, macrocephalus, ASD [14,23,24] and gastrointestinal problems [25][26][27][28][29][30][31][32][33][34][35][36][37] appear to be constant features [29,38]. Some reports mention muscle hypotonia, however, in cases of microdeletions it often remains unclear, whether a certain symptom might be caused by CHD8 deficiency per se or by derangement of neighbouring genes [25].…”