COACH-Syndrome – A very rare (?) differential diagnosis of vermis hypoplasia

Joubert's Syndrome was so far the classical diagnosis of severe vermis hypoplasia associated with molar tooth malformation of the brainstem including psychomotor developmental delay and ataxia.

In the last few years a lot of variants of Joubert's Syndrome were described, also COACH-Sydrome (cerebellar vermis hypoplasia, oligophrenia, ataxia, coloboma, hepatic fibrosis), first reported 1989 by Verloes and Lambote.

We report three children of two families, who finally were found to show the distinct conditions of COACH-Syndrome.

Patient 1 was admitted to our hospital first at the age of 3 months with irregular eye movements and impaired capacity of hearing, followed by mental developmental delay and muscular hypotonia. The patient was found to have coloboma and severe cerebellar vermis hypoplasia. Neurometabolic investigations including CDT were normal. At the age of 18 months the patient first showed a hepatic involvement with elevated liver enzymes. No abnormalities of the O-glycosylation was found, muscle- and skinbiopsy revealed normal. At the age of 40 months a liver biopsy confirmed the suspected diagnosis of COACH-Syndrome with detection of an early stage of cirrhosis with septal fibrosis and pseudolobules.

Patient 2 was a 14 month old girl of related parents, who showed a psychomotor developmental delay associated with ataxic gait, breathing dysregulation, myopia, strabism and choroidoretinal coloboma. MRI findings included severe vermis hypoplasia with typical malformation of the 4. ventricle and the brainstem. Liver function and structure still remain normal.

Patient 3 we saw at the age of 4 years after his sister (patient 2) showed the typical symptoms of first presumed Joubert's Syndrome. He was also found to show the typical radiological abnormalities associated with retrobulbar cysts and optic atrophy as well as psychomotor retardation with ataxic gait. Routine laboratory investigations suggested hepatopathy at the age of 13 9/12. A liver biopsy revealed similar previous described histological abnormalities.

COACH-Syndrome is a very rare disorder. So far 19 cases were discribed (Uemura et al.). Genetic etiology is still unknown. The responsible gene could not be detected so far.

The initially symptoms consist of variable neurological problems associated with the radiological abnormalities leading to early diagnosis of Joubert's Syndrome. Furtheron neurodevelopment becomes stable and is followed by liver and renal insufficiency – the limiting features .

For treatment actually just an early supplementation with ursodeoxycholic acid is known.

Liver transplantation seems to be the ultimate choice.