[Cerebellar vermis hypoplasia with extracerebral involvement (retina, kidney, liver): difficult to classify...

Congenital cerebellar vermis hypoplasias diversely associated with retinopathy, nephropathy and hepatopathy are rare syndromes of uncertain nosology. We report three new cases.

Case 1. A 3-month-old boy presented a brief nystagmus. At the age of 2 years, he had facial dysmorphia, hypotonia, ataxia, ocular motor apraxia and neurodevelopmental impairment with cerebellar vermis hypoplasia. The electroretinogram showed asymptomatic retinal involvement. At the age of 6 years, he developed chronic renal failure. The diagnosis of familial juvenile nephronophthisis was made by detection of a large homozygous deletion of the NPH1 region. Case 2. A term newborn boy presented apnea, tachypnea, hypotonia, nystagmus, ptosis, lack of visual contact and hepatomegaly. He had facial dysmorphia, bilateral optic coloboma with chorioretinal dysplasia and cerebellar vermis hypoplasia. There were cysts in the kidneys with increased echogenicity and lack of demarcation between the pyramids and the cortex. The liver was hyperechoic with fibrosis. At the age of 15 months, the child had severe developmental delay. He had bouts of fever. A search for a large homozygous deletion of the NPH1 region was negative. Case 3. A term newborn girl presented difficulty to suck, cyanosis, hypotonia and ptosis. Later, the child had a developmental delay. At the age of 6 years, she developed chronic renal failure (nephronophthisis). At the age of 23 years, she presented divergent strabismus, ataxia, mental retardation, slow ocular pursuit and facial dysmorphia. The neuroimaging showed a cerebellar vermis hypoplasia. A search for a large homozygous deletion of the NPH1 region was negative.

The diagnosis of cerebellar vermis hypoplasia requires searching for retina, kidney and liver involvement. The large homozygous deletion of the NPH1 region has to be investigated if typical familial juvenile nephronophthisis is associated. Because cerebellar vermis hypoplasia with extracerebral involvements (retina, kidney, liver) is part of many different closely related syndromes, a clear molecular classification is necessary for accurate genetic counselling and an early prenatal diagnosis.