A genome-wide screening was conducted in a consanguinous Algerian family with 3 children with multicore disease at the Groupe Hospitalier Pitie-Salpetriere, Paris, France, and other centers. This recessive disease presented in infancy with moderate predominantly axial weakness, affecting pelvic girdle and hands, joint hyperlaxity, and multiple short-length core lesions (minicores) in both muscle fiber types. The disease was mapped to chromosome 19q13 in this family and in 3 additional families with a similar phenotype. In the Algerian family, a novel homozygous missense mutation (P3527S) was identified in the ryanodine receptor type 1 gene, responsible for autosomal dominant congenital myopathy central core disease. New muscle biopsies performed on reaching adulthood showed typical central core disease with rods. This subgroup of families linked to 19q13 is the first variant of central core disease with genetically proven recessive inheritance and transient early presentation as multi-minicore disease. [1]
COMMENT. Multi-minicore disease (MmD) and central core disease (CCD) are congenital myopathies that present with neonatal hypotonia, delayed motor development, and generalized muscle weakness and amyotrophy that are non- or slowly progressive. MmD is autosomal recessive and CCD is autosomal dominant in inheritance. The above study of families provides genetic evidence that MmD is a variant of CCD with autosomal recessive inheritance and transitory expression as MmD.
Congenital myasthenic syndrome (CMS) caused by a newly identified chromosomal microdeletion and N-box mutation of the AChRe gene is reported from Ludwig-Maximilians-University, Munich, Germany [2]. CMSs are a heterogeneous group of disorders with impaired neuromuscular transmission due to various inherited defects. This is the first report of a chromosomal microdeletion affecting an AChR gene in skeletal muscle.
Therapies for disorders of the neuromuscular junction are reviewed in an editorial [3]. These are of 2 types: 1) symptomatic treatment with cholinesterase inhibitors and plasmapheresis; and 2) immunotherapy (immunosuppressant medications), immunomodulating therapy (immunoglobulin (Ig) G), and thymectomy. The most promising approach is the development of more specific and less toxic immunosuppression therapies.