Cerebellar vermis hypoplasias with extracerebral involvement (retina, kidney, liver): difficult to classify syndromes

Congenital cerebellar vermis hypoplasias diversely associated with retinopa thy, nephropathy and hepatopathy are rare syndromes of uncertain nosology. We report three new cases. Case reports. - Case 1. A 3-month-old boy presented a brief nystagmus. At t he age of 2 years, he had facial dysmorphia, hypotonia, ataxia, ocular moto r apraxia and neurodevelopmental impairment with cerebellar vermis hypoplas ia. The electroretinogram showed asymptomatic retinal involvement. At the a ge of 6 years, he developed chronic renal failure. The diagnosis of familia l juvenile nephronophthisis was made by detection of a large homozygous del etion of the NPH1 region. Case 2. A term newborn boy presented apnea, tachy pnea, hypotonia, nystagmus, ptosis, lack of visual contact and hepatomegaly . He had facial dysmorphia, bilateral optic coloboma with chorioretinal dys plasia and cerebellar vermis hypoplasia. There were cysts in the kidneys wi th increased echogenicity and lack of demarcation between the pyramids and the cortex. The liver was hyperechoic with fibrosis. At the age of 15 month s, the child had severe developmental delay. He had bouts of fever. A searc h for a large homozygous deletion of the NPH1 region was negative. Case 3. A term newborn girl presented difficulty to suck, cyanosis, hypotonia and p tosis. Later, the child had a developmental delay. At the age of 6 years, s he developed chronic renal failure (nephronophthisis). At the age of 23 yea rs, she presented divergent strabismus, ataxia, mental retardation, slow oc ular pursuit and facial dysmorphia. The neuroimaging showed a cerebellar ve rmis hypoplasia. A search for a large homozygous deletion of the NPH1 regio n was negative. Conclusion. - The diagnosis of cerebellar vermis hypoplasia requires search ing for retina, kidney and liver involvement. The large homozygous deletion of the NPH1 region has to be investigated if typical familial juvenile nep hronophthisis is associated. Because cerebellar vermis hypoplasia with extr acerebral involvements (retina, kidney, liver) is part of many different cl osely related syndromes, a clear molecular classification is necessary for accurate genetic counselling and an early prenatal diagnosis. (C) 2001 Edit ions scientifiques et medicales Elsevier SAS