G.P.73 Abnormal neuromuscular transmission in infants with Prader–Willi syndrome

Abstract

Abstract Prader–Willi Syndrome (PWS) is a multi-system disorder caused by absent expression of the paternal region of chromosome 15q11–13. Newborns with PWS are severely hypotonic and inactive, with subtle dysmorphic features (almond shaped eyes, small hands and feet and hypogonadism). Ability to suck is reduced and feeding problems are common, however respiratory distress is rare. Characteristically, within weeks, these infants become more responsive and develop more spontaneous movement. The aetiology of the extreme hypotonia is unknown, however both central factors and primary muscle pathology have been proposed. We describe five infants with severe hypotonia, feeding difficulties and varying degrees of respiratory distress. The diagnosis of PWS was initially not clinically apparent therefore they underwent neurophysiological assessment, including stimulated single fibre EMG (SSFEMG) of orbicularis oculi. SSFEMG was considered abnormal if the grand average of the mean consecutive difference (MCD), of the intervals between the stimulus and the potential (the jitter), was greater than 26 μs, or if more than 10% of the individual measurements were greater than 34 μs. All five infants showed significant abnormalities in SSFEMG, suggestive of a neuromuscular transmission disorder. Jitter measurements ranged from 34.6 to 68.7. One infant was initially diagnosed with congenital myasthenic syndrome and responded well to treatment with pyridostigmine. Cytogenetic studies subsequently confirmed the diagnosis of PWS in all five cases. This is the first report of abnormal SSFEMG findings in infants with PWS. We suggest that these infants may have an abnormality in neuromuscular junction transmission contributing to their early hypotonia and inactivity, which improves with maturation. PWS should therefore be considered in the differential diagnosis of hypotonic infants with neuromuscular junction abnormalities diagnosed by SSFEMG.