Background
Phocomelia is an extremely rare congenital malformation that emerged as one extreme of a
range of defects resulting from in utero exposure to thalidomide. Individuals with thalidomide
embryopathy (TE) have reported developing symptoms suggestive of peripheral nervous
system dysfunction in the mal-developed limbs in later life.
Methods
Case control study comparing TE subjects with upper limb anomalies and neuropathic
symptoms with healthy controls using standard neurophysiological testing. Other causes of
a peripheral neuropathy were excluded prior to assessment.
Results
Clinical examination of 17 subjects with TE (aged 50.4±1.3 [mean±standard deviation]
years, 10 females) and 17 controls (37.9±9.0 years; 8 females) demonstrated features of
upper limb compressive neuropathy in three-quarters of subjects. Additionally there were
examination findings suggestive of mild sensory neuropathy in the lower limbs (n = 1), L5
radiculopathic sensory impairment (n = 1) and cervical myelopathy (n = 1). In TE there were
electrophysiological changes consistent with a median large fibre neuropathic abnormality
(mean compound muscle action potential difference -6.3 mV ([-9.3, -3.3], p = 0.0002) ([95%
CI], p-value)) and reduced sympathetic skin response amplitudes (-0.8 mV ([-1.5, -0.2], p =
0.0089)) in the affected upper limbs. In the lower limbs there was evidence of sural nerve
dysfunction (sensory nerve action potential -5.8 μV ([-10.7, -0.8], p = 0.0232)) and impaired
warm perception thresholds (+3.0°C ([0.6, 5.4], p = 0.0169)).
Conclusions
We found a range of clinical features relevant to individuals with TE beyond upper limb compressive
neuropathies supporting the need for a detailed neurological examination to
exclude other treatable pathologies. The electrophysiological evidence of large and small
fibre axonal nerve dysfunction in symptomatic and asymptomatic limbs may be a result of
the original insult and merits further investigation.