Hereditary Neuropathy - complex

Gene: TUBB3

Green List (high evidence)

14 individuals from 13 families reported with recurrent NM_006086.4 (TUBB3):c.785G>A (p.Arg262His) variant resulting in a distinct phenotype, referred to as the TUBB3 R262H syndrome.

The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations.

While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.

Created: 10 Aug 2023, 4:01 a.m. | Last Modified: 10 Aug 2023, 4:01 a.m.

Panel Version: 0.256

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Fibrosis of extraocular muscles, congenital, 3A (MIM#600638); Neuropathy

Publications

• 34652576

I don't know

CFEOM is characterised by congenital restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. CFEOM3 has a more variable phenotype and some individuals have been reported to present with polyneuropathy and is a rarer form of CFEOM.

PMID: 20074521
Multiple individuals affected from two families with axonal sensorimotor polyneuropathy and a disease associated variant in TUBB3 causative of congenital fibrosis of extraocular muscles-3A (CFEOM3).

Created: 10 Aug 2023, 1:11 a.m. | Last Modified: 10 Aug 2023, 1:11 a.m.

Panel Version: 0.237

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Fibrosis of extraocular muscles, congenital, 3A (MIM#600638)

Publications

• 20074521