Familial and genetic associations in Worster-Drought syndrome and perisylvian disorders.

Worster-Drought syndrome (WDS) is a distinct clinical phenotype, comprising a congenital pseudobulbar palsy usually in association with a mild tetraplegia and often additional impairments. The phenotype is identical to that described in congenital bilateral perisylvian polymicrogyria syndrome (CBPS) and appears to have several different causes and a significant familial incidence. This study draws from a database of children with WDS phenotype or perisylvian polymicrogyria, held at a tertiary center. The findings suggest that genetic factors are important for a significant proportion of children and points to considerable genetic heterogeneity. There are grounds for considering WDS and perisylvian polymicrogyria as a spectrum of perisylvian malfunction.

The first nonsense mutation in alsin results in a homogeneous phenotype of infantile-onset ascending spastic paralysis with bulbar involvement in two siblings.

Eight mutations in the ALS2 gene have been described as causing autosomal-recessive juvenile-onset forms of the motor neuron diseases amyotrophic lateral sclerosis, primary lateral sclerosis and hereditary spastic paraplegia. All mutations are small deletions that are predicted to result in a frameshift and premature truncation of the alsin protein. Here we describe a ninth ALS2 mutation, in two siblings affected by infantile-onset ascending spastic paraplegia with bulbar involvement. This mutation is predicted to result in the substitution of an amino acid by a stop codon, and thus is the first nonsense mutation detected in this gene. It is probable that full-length alsin is required for the proper development and/or functioning of upper motor neurons.

[Atypical CADASIL phenotypes and pathological findings in two new French families]. / CADASIL: aspects phénotypiques inhabituels et observations anatomo-pathologiques dans deux nouvelles familles françaises.

Atypical phenotypes of CADASIL and corresponding anatomical data in two cases are described in 6 members of 2 new French families. In the first family, 4 cases in the same kindred were probably affected, two of them with a predominant psychiatric presentation, two others with dementia and a pseudo-bulbar syndrome of progressive evolution. No history of migraine or ischemic event were documented in any. In the propositus, the diagnosis was documented by skin biopsy, Notch 3 gene mutation and autopsy after the patient had died when 67 years old, 8 years after onset. Brain examination showed a widespread leukoencephalopathy with subcortical infarcts. Characteristic granular lesions of the small arteries of the brain and other organs were observed. In the second family, two cases are reported. One patient died when 63 years old after a subacute evolution mimicking intracranial hypertension. The anatomical diagnosis was retrospectively proven typical of CADASIL with Notch 3 immunostaining of arterial smooth muscle cells. The other case had a progressive evolution over 20 years of limb paresthesia with a mild spasticity diagnosed as a progressive form of multiple sclerosis. It was followed by a pseudo-bulbar syndrome and a mild subcortical dementia without acute ischemic attack. The diagnosis was confirmed by skin biopsy and mutation of the Notch 3 gene. This report illustrates