Importance of Skin Changes in the Differential Diagnosis of Congenital Muscular Dystrophies.

Uluç Yis,Figen Baydan,Semra Hız Kurul,Mert Karakaya,Sebahattin Cirak

doi:10.1155/2016/3128735

Abstract

Megaconial congenital muscular dystrophy (OMIM 602541) is characterized with early-onset hypotonia, muscle wasting, proximal weakness, cardiomyopathy, mildly elevated serum creatine kinase (CK) levels, and mild-to-moderate intellectual disability. We report two siblings in a consanguineous family admitted for psychomotor delay. Physical examination revealed proximal muscle weakness, contractures in the knee of elder sibling, diffuse mild generalized muscle atrophy, and dry skin with ichthyosis together with multiple nummular eczema in both siblings. Serum CK values were elevated up to 500 U/L. For genetic work-up, we performed whole exome sequencing (WES) after Nimblegen enrichment on the Illumina platform. The WES revealed a novel homozygous missense mutation in the Choline Kinase-Beta (CHKB) gene c.1031G>A (p.R344Q) in exon 9. Ichthyosis-like skin changes with intense pruritus and nummular eczema may lead to clinical diagnosis in cases with megaconial congenital muscular dystrophy.

Highlights

The congenital muscular dystrophies (CMD) are a group of diseases that show great clinical and genetic heterogeneity [1]
We report two siblings with megaconial congenital muscular dystrophy and the clinical relevance of skin changes in the differential diagnosis among other congenital muscular dystrophy subtypes
The Cologne Center for Genomics VARBANK pipeline v.2.12 used for data analysis for rare autosomal recessive disease in a consanguineous family revealed an unpublished novel homozygous missense variant in the Choline Kinase-Beta (CHKB) gene c.1031G>A in exon 9 causing p.R344Q according to NM 005198.4 (Figure 1(c))

Summary

Introduction

The congenital muscular dystrophies (CMD) are a group of diseases that show great clinical and genetic heterogeneity [1]. Megaconial congenital muscular dystrophy (OMIM 602541) is characterized with early-onset hypotonia, muscle wasting, proximal weakness, cardiomyopathy, mildly elevated serum creatine kinase levels, and mild-to-moderate intellectual disability [2]. Muscle biopsy shows dystrophic changes and mitochondrial abnormalities. The center of muscle fibers is usually depleted of mitochondria, but the mitochondria are markedly enlarged at the periphery [3]. The disease is caused by the loss-of-function mutations in choline kinasebeta (CHKB). It is suggested that altered phospholipid composition in muscle mitochondrial membrane may lead to mitochondrial structural and functional abnormalities [4]. We report two siblings with megaconial congenital muscular dystrophy and the clinical relevance of skin changes in the differential diagnosis among other congenital muscular dystrophy subtypes

Patients and Genetic Analysis

Discussion

Findings

Conclusion