Clinical spectrum and diagnostic difficulties of infantile ponto-cerebellar hypoplasia type 1

We present the clinical and histopathological features and the diagnostic d ifficulties encountered in five children affected by a motor neuron disorde r other than spinal muscular atrophy. Investigations performed suggested th e diagnosis of pontocerebellar hypoplasia type 1 (PCH-1). Severe respirator y difficulty was present at birth in two of these children; hypotonia, arth rogryposis, microcephaly and nystagmus were present in all; Early and progr essive bulbar involvement with swallowing difficulties and strider was also a common feature in these infants. Severe cognitive delay was invariably p resent. Brain magnetic resonance imaging showed ponto-cerebellar hypoplasia in four children while striking atrophy of the cerebellar vermis and cereb ellar hemispheres were present in the fifth child. Electrophysiological and pathological investigations of proximal muscles performed at presentation in all these children were not conclusive, while the post-mortem studies, o r the study of distal muscles during life, showed a clear neurogenic pictur e, Genetic studies excluded involvement of the SMN gene, or of other genes located on chromosome 5q, confirming that ponto-cerebellar hypoplasia type 1 is a different entity from typical proximal spinal muscular atrophy.