open access

Vol 52, No 2 (2018)
Case reports
Submitted: 2017-10-03
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A missense mutation in DYNC1H1 gene causing spinal muscular atrophy – Lower extremity, dominant

Joyutpal Das, James B. Lilleker, Kavaldeep Jabbal, John Ealing
DOI: 10.1016/j.pjnns.2017.12.004
·
Neurol Neurochir Pol 2018;52(2):293-297.

open access

Vol 52, No 2 (2018)
Case reports
Submitted: 2017-10-03

Abstract

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, which causes progressive muscle weakness and in severe cases respiratory failure and death. Although the majority of the SMA cases are autosomal recessive, there is an autosomal dominant variant of SMA that primarily affects the lower extremities, known as ‘spinal muscular atrophy – lower extremity, dominant’ (SMALED). Mutations in the Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) gene were the first to be associated with SMALED. Here we report a family with SMALED caused by a pathogenic heterozygous missense c.1809 A>T, p.glu603Asp mutation in DYNC1H1. The main clinical features were congenital hip displacement, talipes, delayed motor development, wasting and weakness in lower limbs with relative sparing of upper extremities and very slow disease progression.

SMALED is extremely rare and only a handful of families have been reported. Over the years other phenotypes including Charcot Marie Tooth type 2 and hereditary mental retardation with cortical neural migration defects have also been reported to be caused by DYNC1H1 mutations.

This report aims to increase our awareness of SMALED and various other phenotypes associated with mutations in this gene.

Abstract

Spinal muscular atrophy (SMA) is a hereditary neuromuscular disorder, which causes progressive muscle weakness and in severe cases respiratory failure and death. Although the majority of the SMA cases are autosomal recessive, there is an autosomal dominant variant of SMA that primarily affects the lower extremities, known as ‘spinal muscular atrophy – lower extremity, dominant’ (SMALED). Mutations in the Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) gene were the first to be associated with SMALED. Here we report a family with SMALED caused by a pathogenic heterozygous missense c.1809 A>T, p.glu603Asp mutation in DYNC1H1. The main clinical features were congenital hip displacement, talipes, delayed motor development, wasting and weakness in lower limbs with relative sparing of upper extremities and very slow disease progression.

SMALED is extremely rare and only a handful of families have been reported. Over the years other phenotypes including Charcot Marie Tooth type 2 and hereditary mental retardation with cortical neural migration defects have also been reported to be caused by DYNC1H1 mutations.

This report aims to increase our awareness of SMALED and various other phenotypes associated with mutations in this gene.

Get Citation

Keywords

SMA, SMALED, DYNC1H1, EMG

About this article
Title

A missense mutation in DYNC1H1 gene causing spinal muscular atrophy – Lower extremity, dominant

Journal

Neurologia i Neurochirurgia Polska

Issue

Vol 52, No 2 (2018)

Pages

293-297

DOI

10.1016/j.pjnns.2017.12.004

Bibliographic record

Neurol Neurochir Pol 2018;52(2):293-297.

Keywords

SMA
SMALED
DYNC1H1
EMG

Authors

Joyutpal Das
James B. Lilleker
Kavaldeep Jabbal
John Ealing

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