Three Siblings with Progressive Encephalopathy and Destructive White Matter Lesions

Abstract

Intellectual disability is an important health issue, with a prevalence estimated at 1%. Autosomal genes are increasingly identified as an important cause, although still few of them are known. Most cases are of recessive origin and are found in large consanguineous families in the Middle East.  Mutations in the TRAPPC9 gene have been reported in different families and are associated with a nonsyndromic form of intellectual disability, although phenotypic abnormalities such as a specific facial appearance, obesity, hypotonia and consistent brain abnormalities were linked to these mutations. Here, we describe three siblings of consanguineous Algerian parents with a homozygous c.1708C>T, p. Arg570* mutation in the TRAPPC9 gene. Initially a relatively normal development was seen until the age of 12-18 months, with from then on a progressive degradation of their mental and motor state and the presence of convulsions in two of them. This, in combination with progressive white matter lesions seen on repetitive magnetic resonance imaging, suggests that this TRAPPC9 mutation should not only be considered as a form of intellectual disability, but also as a neurodegenerative disease.