The majority of neuropathy in childhood can be attributed to genetic etiology with a smaller portion to acquired causes (Wilmshurst et al, 2011). Previous data from our center by Malik et al demonstrated 51% of peripheral neuropathy to have genetic causes, while 27% were traumatic, 19% inflammatory, and 4% toxic/metabolic.

We collected prospective data for all individuals seen at a pediatric tertiary care electromyography clinic who also underwent genetic testing prior to or following their evaluation from 2013-2018. We recorded detailed phenotype information, electromyography findings, and molecular diagnostic results.

Seventy seven subjects with abnormal EMG/NCS and clinical suspicion for an inherited polyneuropathy were included. Genetic testing was attempted in all individuals. Twenty seven subjects (34%) had Charcot-Marie-Tooth (CMT1A n=14, CMTX n=4, CMT2A n=3, CMT1B n=2, CMT2S n=2, CMT1E n=1 and CMT2O n=1), nine subjects had HNPP (12%), 22 subjects (28%) had neuropathy associated with neurodegenerative disorders including spastic paraplegia (KIF1A n=2, SPG7 n=1, KIF5A n=1 and ZFYVE26 n=1), ataxias (SCA2 n=3, FXN n=2,  ATM n=2), GAN (n=2), COL6A2 (n=1), and clinically diagnosed Cockayne syndrome (n=1) . Other genetic etiologies included mitochondrial and metabolic conditions attributable to POLG, ARSA, AARS2, HADHA, and LAMA2. Twenty one subjects (27%) with suspected genetic neuropathy remain unconfirmed with genetic testing. PMP22 deletion/duplication analysis and comprehensive CMT panel had high diagnostic yield (67%), followed by inherited neuropathy panel (44%).

Charcot-Marie-Tooth, HNPP and neurodegenerative disorders emerged as the most common causes of genetic neuropathies in childhood. One third of children with suspected genetic neuropathy remain unconfirmed, despite ongoing genetic work up, with exome sequencing to be considered in the future.