Early impairment of somatosensory evoked potentials in very young children with achondroplasia with foramen magnum stenosis.

AIM: To evaluate the contribution of somatosensory evoked potentials after median nerve (MN-SEPs) and posterior tibial nerve (PTN-SEPs) stimulation in functional assessment of cervical and lumbar spinal stenosis in children with achondroplasia. METHOD: We reviewed MN-SEPs, PTN-SEPs, and spinal magnetic resonance imaging (MRI) examinations performed in 58 patients with achondroplasia (25 males, 33 females; age range 21d-16y 10mo; mean age 4y 3mo [SD 4y 1mo]). Patients were subdivided into four age categories: <2 years, between 2 to 4 years, between 4 to 8 years, and ≥8 years. The peak latency of P37 for PTN-SEPs, the peak latencies of N11, N13, P14, and N20, and the N13-N20 interpeak latency (IPL) for MN-SEPs were collected; the diagnostic accuracy measures of these parameters (analysis of receiver operating characteristic [ROC] curves) with respect to the presence of foramen magnum or lumbar spinal stenosis were analysed in each age category. RESULTS: The ROC curve analysis showed that the most sensitive parameter in detecting the presence of foramen magnum stenosis was P37 latency in the first two age categories (<2y and ≥2-4y; sensitivity 0.63, specificity 1.00, and sensitivity 1.00, specificity 0.75 respectively). In the third age category (≥4-8y), the most sensitive parameter in detecting the presence of foramen magnum stenosis was IPLs N13-N20 (sensitivity 0.73, specificity 0.87), whereas in the last age category (≥8y), the most important parameter was N20 latency (sensitivity 0.75, specificity 0.77). INTERPRETATION: In children with achondroplasia, the cortical component of PTN-SEPs is more sensitive than the cortical component and central conduction time of MN-SEPs in detection of cervical spinal cord compression at early ages.

Further genotype-phenotype correlation emerging from two families with PLP1 exon 4 skipping.

Proteolipid protein 1 (PLP1) gene-related disorders due to mutations in the PLP1 include a wide spectrum of X-linked disorders ranging from severe connatal Pelizaeus-Merzbacher disease (PMD) to spastic paraplegia 2 (SPG2). Duplications, deletions or point mutations in coding and noncoding regions of the PLP1 gene may occur. We report the clinical, neuroradiologic and molecular findings in six patients from two unrelated families. The affected males showed severe mental retardation, spastic tetraparesis, inability of walking and pes cavus at onset in early infancy. Brain magnetic resonance imaging (MRI) showed hypomyelination and brain atrophy. Nystagmus was never observed. The affected females showed adult-onset progressive spastic paraparesis leading to wheel-chair dependency and subtle white matter changes on brain MRI. Molecular studies in the two families identified two different intronic mutations, the novel c.622+2T>C and the known c.622+1G>A, leading to the skipping of PLP1-exon 4. The clinical presentation of the affected males did not consistently fit in any of the PLP1-related disorder subtypes (i.e., connatal or classic PMD, SPG2 and 'PLP1 null syndrome'), and in addition, the carrier females were symptomatic despite the severe clinical picture of their respective probands. This study provides new insight into the genotype-phenotype correlations of patients with PLP1 splice-site mutations.