Abstract

The CHL1 (OMIM 607416) is the most distal gene located on the short arm of chromosome 3 and encodes a protein that is a member of the immunoglobulin family. It is highly expressed in the brain and plays an important role in neural migration, neurite outgrowth and synaptogenesis. The gene has been associated with cognitive impairment in individuals with 3p deletions syndrome: a rare contiguous gene syndrome caused by 3p25-pter deletions of variable size and a recognisable phenotype including developmental delay, intellectual disability (ID), dysmorphism, microcephaly and ptosis.

Here, we describe a patient with a submicroscopic 3 p26.3 deletion and a particular phenotype. The patient is a 14 year-old boy who was referred to the Department of Paediatric Neurology for epileptic seizures (tonic generalised seizures); the personal history disclosed a global development delay (GDD) and an autism spectrum disorder (ASD), diagnosed at the age of 2 years, the boy being included in a complex program of therapy (behaviour therapy, speech therapy, ergotherapy, cognitive stimulation).

The clinical evaluation revealed congenital horizontal nystagmus, bilateral myopia, speech delay, mild intellectual disability, autistic behaviour, and hyperkinesia. Electroencephalogram showed sharp waves on left frontal-central derivations; cerebral MRI was normal. Genetic testing (Array-CGH, using Agilent Technologies) was performed on peripheral blood from the patient. We identified a 12 Kb heterozygous deletion at 3 p26.3, with genomic boundaries 270,649–283,052 (hg 38), spanning a part of CHL1 gene.

By our knowledge, 15 cases with 3 p26.3 deletion involving only CHL1 gene have been reported, to date. The most common features seem to be GDD, ID and speech impairment. ASD and epileptic seizures are findings rarely associated with this deletion. Our study supports previously proposals about the role of CHL1 in ASD and epilepsy pathogenesis and brings new evidences for a better correlation between CHL1 deletion and phenotype complexity.