Objective:

We present a case report of a pediatric patient with demyelinating polyneuropathy and leukodystrophy in MPV17 gene mutation. The leukodystrophy and c.284dup (p.Phe96LeufsTer17) variant are novel findings in our patient with Charcot Marie Tooth disease type2EE.

Background:

Charcot Marie Tooth Disease, axonal, type 2EE (OMIM#618400) is an autosomal recessive sensorimotor peripheral axonal neuropathy with slow onset in first or second decades of life. It is caused by homozygous or compound heterozygous mutation in MPV17 gene.

Design/Methods:

NA

Results:

A previously normally developing male child, born of consanguineous marriage, presented at 3 years of age with clinical signs of progressive loss of previously acquired developmental milestones, aphasia, dysphagia, nasal regurgitation of milk, inability to walk and gait disturbance. Neurologic examination showed increased tone and exaggerated reflexes in all limbs. MRI of brain revealed T2W and FLAIR hyperintensities in white matter of both cerebral hemisphere which suggested leukodystrophy. EMG/NCS demonstrated demyelinating polyneuropathy with secondary axonal loss. Whole exome sequencing identified a homozygous single base pair duplication in exon 5 of the MPV17 gene leading to frameshift mutation. The c.284dup (p.Phe96LeufsTer17) variant is classified as pathogenic per ACMG guidelines (PVS1, PM2, PP5). There is family history of similarly affected siblings with death in neonatal period which supported that inheritance pattern is recessive. The child is diagnosed with Charcot Marie Tooth disease type2EE.

Conclusions:

The presence of the variant c.284dup along with leukodystrophy and demyelinating polyneuropathy widens the phenotypic presentation of Charcot Marie Tooth disease type2EE. This case highlights the importance of early genetic testing for improvement of outcomes and family counselling especially in consanguineous families.