Targeted next-generation sequencing in two brothers with congenital muscular dystrophy with rigid spine revealed homozygous missense variants in ACTA1.
Four patients from different Indian families with a distinct clinicoradiologic profile resembling congenital muscular dystrophy with mutations in the GPR56 gene are described.
Here we provide an overview on both pathophysiology and the extremely heterogeneous clinical presentations of the disorders reported so far (Sengers syndrome (due to mutations in AGK), MEGDEL syndrome (or SERAC defect, SERAC1), Barth syndrome (or TAZ defect, TAZ), congenital muscular dystrophy due to CHKB deficiency (CHKB).
Allelic mutations in each of these genes can result in a wide spectrum of clinical conditions, ranging from severe congenital onset with associated structural brain malformations (Walker Warburg syndrome; muscle-eye-brain disease; Fukuyama muscular dystrophy; congenital muscular dystrophy type 1D) to a relatively milder congenital variant with no brain involvement (congenital muscular dystrophy type 1C), and to limb-girdle muscular dystrophy (LGMD) type 2 variants with onset in childhood or adult life (LGMD2I, LGMD2L, and LGMD2N).
The dystroglycanopathies are a heterogeneous group of conditions, with mutations in B3GALNT2 described in association with congenital muscular dystrophy.
Biglycan has been considered a good candidate for neuromuscular disease based on direct interactions with collagen VI and alpha-dystroglycan, both of which are linked with congenital muscular dystrophy (CMD).
Loss of choline kinase activity in muscle causes rostrocaudal muscular dystrophy (rmd) in mouse and congenital muscular dystrophy in human, characterized by distinct mitochondrial morphological abnormalities.
Alteration of mitochondrial membrane inner potential in three Italian patients with megaconial congenital muscular dystrophy carrying new mutations in CHKB gene.
Since our report of CHKB mutations found in 15 cases with megaconial congenital muscular dystrophy from Japanese, Turkish, and British populations, we have further identified two British and one French patients.
Thus the phenotypic spectrum of CHKB mutations ranges from a congenital muscular dystrophy with intellectual disability to a later-onset non-progressive muscular weakness with normal cognition.
Choline kinase β (Chk β) is important for adult muscle homeostasis, as autosomal recessive mutations in CHKβ are associated with two human muscle diseases, megaconial congenital muscular dystrophy and proximal myopathy with focal depletion of mitochondria.
Mutations in the choline kinase beta (CHKB) gene are associated with a congenital muscular dystrophy with giant mitochondria at the periphery of muscle fibers.
Motor and sensory nerve conduction velocities (NCVs) and needle electromyography (EMG) results were reviewed in 26 children with different types of congenital muscular dystrophy (CMD), including patients with mutations in the genes LAMA2, FKRP, and COL6A2.