Late‐onset X‐linked recessive spinal and bulbar muscular atrophy

Abstract

A family is described in which five males have late-onset facial weakness, dysarthria, dysphagia, and slowly progressive proximal weakness. Electrodiagnostic studies and muscle biopsy were compatible with spinal muscular atrophy. This family appears quite similar to several previously reported families with late-onset X-linked recessive spinal and bulbar muscular atrophy. Because of the relative homogeneity of this particular phenotype of spinal muscular atrophy, a single metabolic derangement was sought. Three obligate carriers were studied, and no abnormality was detected. A further family with this condition is briefly discussed.

X-linked bulbo-spinal neuronopathy: a family study of three patients.

“…Only one obligate carrier has an elevated creatine kinase level, although III 10, the daughter of an obligate carrier, had a level at the upper limit of normal suggesting that she may be a carrier, but we suspect that creatine kinase levels will not be of value in identifying possible carriers, a conclusion shared by Ringel and colleagues. 4 We have confirmed the findings of Harding and colleagues of the involvement of sensory pathways in this disorder. The sural nerve histology showed evidence of axonal degeneration and segmental demyelination, together with marked endoneural fibrosis, these features being indicative of a chronic neuropathy.…”

“…Electrocardiograms showed no evidence of a conduction abnormality although this has been reported in previous patients. 4 The results of the creatine kinase levels are shown in table 1. All three patients had elevated creatine kinase levels, which is a consistent finding in this disorder.…”

X-Linked Spinal and Bulbar Muscular Atrophy of Late Onset (Kennedy-Stefanis Disease?)

“…It is beyond the scope of this report to reexamine the arguments which led us to sup port that X-linked spinal and bulbar muscu lar atrophy of late onset is a separate type of motor neuron disease [Stefanis et al, 1975], However, we decline from including in this clinical entity, cases with distal distribution of muscle atrophy and weakness as Ringel et al [1978] have done lately.…”

“…The patients in this report suffer from Xlinked spinal and bulbar muscular atrophy of late onset [Kennedy et al" 1968;Stéfanis el al" 1968Stéfanis el al" , 1973aStéfanis el al" , b, 1975Papapetropoulos, 1969;Tsukagoshi et al" 1970;Ringel et al" 1978;Scoenen et al" 1979], An autosomal recessive inheritance in this family cannot be excluded but is most unlikely in view of the fact that all our cases from Greece originate from the same small geographical area; the X-linked inheritance of the disease is proven in family F of our previous reports [Stefanis etal., 1968[Stefanis etal., , 1973a[Stefanis etal., , b, 1975Papapetropoulos, 1969], It is worthwhile noting that 3 out of the 8 living patients, described here and in pre vious reports [Papapetropoulos. 1969, Ste fanis et al" 1975 suffered from infrequent episodes of transient weakness which oc curred before the symptoms of the disease were apparent (Cases 2 and 5 in Stefanis et al [1975] and Case 1 of this report).…”

REVIEW ARTILCE: Cell therapy and stem cells in animal models of motor neuron disorders

“…In ALS, motor neurons in the spinal cord, brain stem and cortex die. In SBMA, degeneration is more restricted, with spinal and brain stem motor neurons dying, but not cortical motor neurons (Kennedy et al ., 1968; Ringel et al ., 1978), while in SMA and SMARD1, only spinal motor neurons are affected. In future cellular therapies aimed at replacing endogenous motor neurons, the location and number of implantation sites as well as the subtypes of motor neurons that need to be generated will thereby differ greatly between these diseases.…”