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

Abstract

SUMMARY The clinical features of two brothers and one nephew with X-linked recessive bulbospinal neuronopathy are described. The neurophysiological investigations and sural nerve biopsy, previously unreported, confirmed that both motor and sensory nerves are affected. Because of the genetic implications, the importance is stressed of recognising this disorder as a separate entity which should not be classified with the spinal muscular atrophies.In 1968, Kennedy and colleagues' reported II males from two families with a distinct form of bulbar and spinal muscular atrophy which was slowly progressive and inherited as an X-linked recessive. Since then a further 31 patients have been described in five separate reports,2 -6 ten being described by Harding and colleagues6 in 1982. As well as reporting similar findings to Kennedy's, they found reduced or unrecordable sensory nerve action potentials in seven patients and because of this abnormality they named it X-linked recessive bulbo-spinal neuronopathy.X-linked recessive bulbo-spinal neuronopathy is a slowly progressive disorder which develops between the third and fifth decades. Muscle wasting and weakness, which is often preceded by cramps for many years, commonly starts proximally in the limbs and then progresses to involve the masticatory, facial and bulbar musculature. Distal wasting and weakness occurs more commonly in the arms. Fasciculations are prominent in the peri-oral region and tongue as well as being generalised. Tendon areflexia is invariable at an advanced stage. A fine tremor of the outstretched hands may predate the onset of muscle weakness, gynaecomastia is a common finding and there is an increased incidence of diabetes mellitus, both in affected patients and in their first degree relatives. Patients have a normal life expectancy.We report three patients with this disorder (fig 1),

Distinguishing clinical and electrodiagnostic features of X-linked bulbospinal neuronopathy

“…13,20 We believe the finding of absent or low amplitude sensory nerve action potentials (SNAPs) in association with clinically normal sensation is virtually unique to XLBSN, and was present in nearly all patients in our review who had careful sensory nerve conduction studies performed when response amplitude was a criteria for abnormality. 2,7,8,11,14,18,23,24,26 Pathologic studies have demonstrated that the major pathologic process in sensory fibers is a distal axonopathy with neuronal and axonal atrophy. 16,23 There is preservation and even increases in the density of small myelinated fibers in some patients with XLBSN, suggesting the presence of regenerated axons among these small fibers.…”

Assessment of upper and lower motor neurons in Kennedy's disease: Implications for corticomotoneuronal PSTH studies

“…19,30,36 These abnormalities are considered to be the result of dorsal root ganglion involvement, and postmortem studies have shown histological features of a dying-back process due to disease of the dorsal root ganglia. 23,30,43,45 Ferrante and Wilbourn 19 propose that ''bulbospinal sensorimotor neuronopathy'' might better describe Kennedy's disease.…”

Preventing the Androgen Receptor N/C Interaction Delays Disease Onset in a Mouse Model of SBMA

“…Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease that is a member of this family and is caused by the expansion of a polymorphic CAG tract in the androgen receptor ( AR ) gene (La Spada et al, 1991). Men with an expansion of the repeat beyond 39 CAGs exhibit proximal muscle weakness and atrophy, muscle fasciculations, dysphagia and dysarthria, and largely subclinical sensory deficits, beginning in the third to fifth decade of life (Harding et al, 1982; Li et al, 1995; Sobue et al, 1989; Wilde et al, 1987). Histological analysis reveals a loss of lower motor neurons from the brain stem and spinal cord and the nuclear accumulation of polyQ-expanded AR within inclusions in neuronal (and to a lesser extent non-neuronal) tissues (Li et al, 1998a; Li et al, 1998b).…”