Progressive cerebellocerebral atrophy: a new syndrome with microcephaly, mental retardation, and spastic quadriplegia.

The combination of microcephaly, spasticity, and profound mental retardation is usually found in children with severe perinatal asphyxia or congenital infection. These children are commonly diagnosed as having cerebral palsy. However, in some children there is no evidence of a perinatal insult and there may be familial recurrence. The London Dysmorphology Database offers 104 genetic syndromes that include these features. However, most of them also show dysmorphism and other organ involvement. Twenty-three of these syndromes are the result of an identified inborn error of metabolism. In some genetic syndromes the microcephaly may be progressive and brain neuroimaging may show cortical or cerebellar atrophy. Cerebellar atrophy can be associated with spasticity and profound mental retardation in pontocerebellar hypoplasia type 2 (PCH 2). We describe seven patients from six non-consanguineous Sephardi Jewish families with a previously undescribed syndrome of profound mental retardation, progressive microcephaly, and severe spasticity. Radiologically, repeat magnetic resonance imaging showed progressive cerebellar atrophy followed by cerebral atrophy involving both white and grey matter. An extensive metabolic evaluation was normal.