The NUDT2 gene, located on the chromosome 9, encodes the NUDIX Hydrolase 2 enzyme. Mutations in NUDT2 have been linked to intellectual disability and developmental delays.

We report case of a 23-year-old man with cognitive and motor developmental delays presenting with distal upper and lower extremity weakness. Symptoms started at age 6 months. Similar symptoms were found in his 10-year-old sister. No parental consanguinity was reported.

Motor examination showed atrophy and weakness of the dorsiflexors and plantar flexors along with diminished reflexes and an everted steppage gait. Sensory examination was abnormal with decreased pinprick and vibration sense in the legs and hands bilaterally. Neurocognitive testing indicated mild intellectual disability with FSIQ of 60.

MRI of the brain and spine and genetic testing for various neurological disorders was unrevealing. Sural nerve biopsy showed chronic neuropathy with large/small myelinated fiber loss. Vastus lateralis biopsy demonstrated mild denervation changes. Electromyography studies of the upper and lower extremities showed severe sensorimotor polyneuropathy with axonal and demyelinating features. Whole genome sequencing identified a homozygous frameshift variant in NUDT2 (c.186delA,p.Ala63Glnfs*3). The patient’s affected sister was found to harbor the same homozygous variant while both parents were identified as carriers.

We report a case of neurodevelopmental disease with cognitive and motor delay and peripheral neuropathy secondary to a homozygous frameshift in the NUDT2 gene, thus extending the previously reported phenotype. Mutation of NUTDT2 should be considered in patients presenting with intellectual disability with or without motor delay and peripheral neuropathy.