Pelizaeus Merzbacher Disease (PMD) is an X-linked dysmyelinating or hypomyelinating disorder leading to abnormal myelination due to mutations of the proteolipid protein 1 (PLP 1) gene on Xq22. This results in a range of phenotypes that form a clinical spectrum from the more severe PMD to the relatively mild X-linked SPG2.

1. Case 1: 34 year old man presented to our clinic with a 2-year history of progressive hand tremor, cognitive decline, and limb spasticity. He was born full term but prolonged delivery, requiring neonatal ICU. He had normal early developmental milestones but slow to walk. He was diagnosed with Cerebral Palsy at age 4, by age 33 he became wheelchair-bound. On examination, he had a left torticollis, broken pursuit, intention tremor and spasticity in lower limbs.
2. Case 2: 29 year old man, presented with his brother (Case 1) with hand tremor and progressive cognitive decline. He was born full-term, normal delivery; but had abnormal early milestones from birth including jerky eyes, titubation and late crawling. He was diagnosed with Ataxic Cerebral Palsy within the first year of life and wheelchair-bound by age 9. On examination, he had titubation, action tremor, nystagmus, dysarthria and spasticity involving all limbs.

There was no family history of genetic disorder or similar symptoms prior to their births.

MRI Brain showed leukodystrophy in both cases. Genetic analysis revealed a pathogenic mutation in the PLP1 gene(c454-322G>A;P?) confiriming a diagnosis of Pelizaeus Merzbacher Disease.

Both patients were misdiagnosed as cerebral palsy due to the phenotypic similarities between PMD and cerebral palsy; especially in early childhood. The delayed progression of their symptoms and lack of family history led to the difficulty in diagnosis. Therefore we should look beyond Cerebral Palsy and consider PLP- related diseases in boys with cerebral-palsy-like features regardless of a lack of family history.