Facioscapulohumeral Muscular Dystrophy: Clinical Diversity and Genetic Abnormalities in Japanese Patients.

Abstract

We studied 71 Japanese individuals, 42 patients (30 familial and 12 sporadic) suspected to have facioscapulohumeral muscular dystrophy (FSHD) and 29 family members, clinically and genetically using the chromosome4qter DNAmarker pl3E-ll. Early onset FSHDwas detected in 7patients, tortuosity of retinal arterioles and hearing impairment in 3 patients, progressive respiratory failure in 3 patients and limb-girdle type muscular weakness in 6 patients. Thirty-six (85.7%) FSHDpatients, 3 asymptomatic family members and 1 of 35 healthy volunteers showed EcoRI digestion fragments shorter than 28kb. Newmutations were detected in 25%of the patients with shorter EcoRI fragment. The age of disease onset appeared younger with successive generations in 6 parent-child pairs in FSHDfamilies. Weconfirmed the existence of phenotypic and genetic diversities in Japanese patients with FSHD.It is still difficult to explain the phenotypic diversity merely by the size of the abnormal EcoRI fragment detected with the pl3E-ll probe.

Risk of functional impairment in Facioscapulohumeral muscular dystrophy

“…28 That said, there is a subgroup of patients, typically with the largest contractions and earliest onset of disease, who require hearing aids. 29,30 The patient-reported risk of extramuscular manifestations of FSHD seen here was also infrequent and did not track with D4Z4 contraction size, with the exception of hearing aid use, which was higher in participants with contractions 18kb. However participants may underreport extramuscular manisfestations, as they may be asymptomatic or slightly symptomatic, and they may not consult a physician to have these manifestations diagnosed.…”

“…One study suggested the level of hearing impairment is no greater than what would be expected for age . That said, there is a subgroup of patients, typically with the largest contractions and earliest onset of disease, who require hearing aids …”

Autosomal-dominant familial hematuria with retinal arteriolar tortuosity and contractures: A novel syndrome

“…Retinal arteriolar tortuosity has also been exceptionally reported in facio-scapulo-humeral dystrophy (FSHD), an autosomal-dominant muscular disorder characterized by proximal muscle weakness, amyotrophia, and contractures [23,24]. Linkage with the FSHD locus (4q35ter) was excluded in our family.…”

Conditional over-expression of PITX1 causes skeletal muscle dystrophy in mice

“…While myofiber atrophy due to denervation/renervation generally involves “grouped” angular-shape atrophic fibers, atrophic myofibers with a myogenic cause tend to be scattered (Banker, 1986; Benedetti et al, 2005). The angular myofibers in FSHD were proposed to be due to a myogenic cause due to their scattered distribution (Engel and Kossman, 1963; Lin and Nonaka, 1991; Nakagawa et al, 1997). We observed the same scattered distribution of angular-shaped myofibers in the Pitx1 transgenic mice muscles.…”