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Pontocerebellar hypoplasia type 1
Pontocerebellar hypoplasia type 1 (PCH1), also known as Norman's disease, is a clinically and genetically heterogeneous group of autosomal recessive disorders with a prenatal onset characterized by diffuse muscular atrophy secondary to pontocerebellar hypoplasia and spinal cord anterior horn cell degeneration resulting in early death.
Incidence is unknown. About 40 patients with PCH1 have been reported.
The clinical course is severe. PCH1 is characterized prenatally often by polyhydramnios with arthrogryposis mutiplex congenital. Neonates with PCH1 present with hypotonia, impaired swallowing with consequently feeding difficulties and progressive microcephaly which mostly develops postnatally. Subsequently a severe psychomotor deficit becomes apparent, if patients survive past infancy oculomotor manifestations become apparent such strabismus, nystagmus, occulomotor apraxia.
Etiology of PCH1 is for the most part unknown. To date recessive mutations have been noted in the EXOSC3 gene (30-40% of the PCH1 cases) and, in single cases, recessive mutations have been found in the tRNA splicing endonuclease homolog 54 (TSEN54), mitochondrial arginyl-transfer RNA synthetase (RARS2), and in the vaccinia-related kinase 1 (VRK1) gene.
MRI shows pontocerebellar hypoplasia with cerebellar hemispheres variably affected and may show spinal anterior horn degeneration. Lack of awareness often results in a delay in diagnosis or a diagnosis is never made.
PCH1 has an autosomal recessive transmission.
Prognosis is poor; the majority of patients will only live into infancy. Patients with EXOSC3 mutation have a less severe prognosis.