Distal spinal muscular atrophy type 1

Distal spinal muscular atrophy type 1 (DSMA1), also known as spinal muscular atrophy with respiratory distress type 1 (SMARD1) and hereditary motor neuropathy type 6 (HMN6) — is a rare neuromuscular disorder involving death of motor neurons in the spinal cord and subsequent generalised atrophy of body muscles. The condition is caused by a genetic mutation in the IGHMBP2 gene and is inherited in an autosomal recessive manner.

Various classifications include DSMA1 variously among spinal muscular atrophies or distal hereditary motor neuropathies, even though the latter has been argued more correct.

Symptoms
Symptoms can sometimes become apparent before birth with the foetuses displaying growth retardation and reduced movements; premature birth is a relatively common occurrence. Newborn babies present weak cry, reduced muscle tone and sometimes deformities. Due to progressive paralysis of the diaphragm, severe respiratory distress usually develops before six months of life – although patients with juvenile onset have also been described. Characteristic is pattern of breathing (the stomach draws inward with inspiration) that indicates weakness of the diaphragm. Deep tendon reflexes become absent. Progressive weakness, at first affecting distal muscles, ultimately renders the patient unable to move. Respiratory support (mechanical ventilation) is required in most cases and long-term prognosis is usually negative.

Whilst symptoms may resemble a case of severe spinal muscular atrophy (SMA type 0 or I), in early SMA the diaphragm is strong and the stomach prominently protrudes with inspiration ("paradoxic breathing pattern").

Therapy
As with many genetic diseases, there is no known cure for DSMA1, although research continues. Supportive care includes respiratory support and various forms of physiotherapy that help delaying muscle wasting.