Laing early-onset distal myopathy in a Belgian family

Laing distal myopathy with a novel mutation in exon 34 of the MYH7 gene

“…Typical features such as foot drop with marked plegia of the big toe and paresis of extension of single fingers have been described previously as a hallmark of Laing myopathy (8). The onset at age 20 to 30 and the rather mild course with preservation of ambulation fits well with previously reported cases, although more severe phenotypes have also been described (16). The fact that involvement of the quadriceps muscle was present only in our oldest patient leaves the possibility that such quadriceps involvement may develop and lead to a more severe degree of gait impairment at an older age.…”

“…There have been only a few families encountered worldwide with genetically proven Laing myopathy (1, 2,3,4,6,7,9,10,11,12,13,14,16). Here, we describe a four-generation family with four affected members in 2 generations with Laing myopathy and additional features with a mutation in exon 34 of the MYH7 gene that has not as been reported so far.…”

Complex sarcolemmal invaginations mimicking myotendinous junctions in a case of Laing early‐onset distal myopathy

“…Interestingly, the p.Glu1508del patient cohort described to date also shows a significant clinical variability: while all patients presented with classic bilateral foot drop at an early age, the involvement of other muscle groups and the speed of disease progression were highly variable. In particular, the disease manifestations in the Belgian family appear to be quite severe, while the family described in the current report manifests a very mild clinical course: for example, the proband (currently age 41) is actively involved in multiple sports and continues to play cello professionally despite the development of mild finger extensor weakness; his father (II/5), a school orchestra conductor for 40 years, continues to regularly walk, bike, and lift weights at the age of 66. These discrepancies between genotype and phenotype suggest a significant role for the genetic background / modifier genes in MPD1 pathogenesis, a feature of the disease that will need to be explored in future studies.…”

“…Sequencing of the MYH7 gene demonstrated the presence of a heterozygous c.4522_4524delGAG (p.Glu1508del) mutation in the proband and three other affected members of his family; this mutation was previously linked to MPD1 in: (i) a French family, a Norwegian family and a single Finnish patient; (ii) a Belgian family; and (iii) another US family . Interestingly, muscle biopsies from other patients with p.Glu1508del mutation showed no unusual morphologic features and were not described as harboring MTJ‐like structures; a similar lack of correlation between genetics and muscle pathology has been observed with two other MPD1 mutations (p.K1729del and p.Leu1597Arg).…”

“…The sequencing revealed heterozygous deletion of a GAG triplet at position 4522‐4524 (Fig. ); this mutation is predicted to result in the loss of a glutamate residue at position 1508 of the beta myosin heavy chain protein (c.4522_4524delGAG (p.Glu1508del)) and has already been linked to MPD1 in several unrelated families throughout the world . The same heterozygous mutation was present in the affected family members III/4, IV/2 and IV/3, while the unaffected family member IV/1 showed a normal MYH7 genotype.…”