“Pelizaeus–Merzbacher-like disease” presenting as complicated hereditary spastic paraplegia

Abstract

Pelizaeus–Merzbacher-like disease (PMLD) is an autosomal recessive leukodystrophy caused by GJC2 gene mutations [1]. Clinical and genetic heterogeneity has been reported for the GJC2 gene that encodes the gap junction protein connexin 47 [1]. PMLD is typically characterized by impaired motor development, nystagmus, progressive spasticity, ataxia, and choreoathetosis in early infancy. Recently, a milder phenotype with late-onset and slowly progressive symptoms has been described [2]. Here we report an unusual case presenting with segmental dystonia and leg spasticity. This 38-year-old patient presented with involuntary head turning and tilting as well as difficulties with handwriting starting in his early twenties. At the age of 29 years, he also began to notice progressive gait slowing and leg stiffness. Of note, the patient was diagnosed with cervical neuroblastoma located anterior to the left sternocleidomastoid muscle at birth, which was operated on in the post-partum period. He was then also treated with chemotherapy (vincristine, cyclophosphamide) and radiation (total dose 19.2 Gy). Motor and language milestones were slightly delayed. He could walk at the age of 15 months and speak at 24 months. He had mild learning impairments at school but was able to complete junior high school. Family history was reported to be negative. On neurological examination, ocular pursuit was slightly saccadic but eye movements were otherwise normal. As sequelae of neuroblastoma surgery he had left Horner syndrome. He had right torticollis, left laterocollis, and dystonic posturing when holding out the arms. He also had bilateral dysdiadochokinesia and mild dysmetria. There was no weakness but marked leg spasticity with brisk deep tendon reflexes, positive Babinski sign, and a scissors-like gait (video). Neuropsychological evaluation revealed mild impairment of executive function, selective attention, and word fluency. MRI showed leukoencephalopathy with diffuse bilateral hyperintense white matter signal on T2-weighted images, which was mild in the central and occipital cerebral white matter but more marked in the posterior limbs of the internal capsule (Fig. 1), consistent with hypomyelination. In the brain stem and mesencephalon, several tracts including pyramidal tracts and medial lemniscus were hyperintense on T2-weighted images. This was also true for the middle cerebellar peduncles. The globus pallidus, red nucleus, substantia nigra, and dentate nucleus appeared relatively hypointense bilaterally. Sagittal images showed thinning of the corpus callosum. Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6617-0) contains supplementary material, which is available to authorized users.