Periventricular Nodular Heterotopia 8

A number sign (#) is used with this entry because of evidence that periventricular nodular heterotopia-8 (PVNH8) is caused by heterozygous missense mutation in the ARF1 gene (103180) on chromosome 1q42.

Description

Periventricular nodular heterotopia-8 (PVNH8) is a neurologic disorder characterized by abnormal neuronal migration during brain development, resulting in delayed psychomotor development. Three patients have been reported (Ge et al., 2016).

For a phenotypic description and a discussion of genetic heterogeneity of periventricular heterotopia, see PVNH1 (300049).

Clinical Features

Ge et al. (2016) identified 3 unrelated individuals with periventricular heterotopia. The first patient was a 9-year-old boy with developmental disabilities, speech delay, and attention deficit-hyperactivity disorder in whom previous genetic tests had been nondiagnostic. There was no history of seizures. Brain MRI showed periventricular heterotopias and diminished white matter. The second patient was a female who had seizures and developmental delays, especially in speech. When evaluated at age 15 years, she had spasticity and had regressed in language abilities. Brain MRI showed periventricular heterotopia, delayed myelination, cortical thinning, and vermis atrophy. There was limited information on the third patient other than the presence of seizures, periventricular heterotopia, delayed myelination, and significant cerebral underdevelopment.

Molecular Genetics

In 3 unrelated patients with periventricular heterotopia, Ge et al. (2016) identified 3 de novo missense mutations in the GDP/GTP binding domain of the ARF1 gene (103180.0001-103180.0003). The mutations were identified by exome sequencing followed by prioritization of candidate genes that contained regions that were missense depleted, i.e., devoid of missense variation in the normal adult population.