The diagnosis is based on moderate mental retardation
associated with early-onset ataxia and hypotonia, inconstant coloboma, and
hepatic cirrhosis in association with a positive family history. Imaging
studies show cerebellar vermis hypoplasia or aplasia but normal
supratentorial structures. Liver biopsy characteristically reveals
periportal fibrosis, cholestasis, reduced number of intrahepatic bile ducts,
and chronic inflammatory infiltrates. Other features may involve the head
and neck (flat round face, hypertelorism, ptosis, optic nerve coloboma and
optic disc atrophy, upturned nose, macrostomia, macroglossia, occipital encephalocele),
the central nervous system (ataxia and hypotonia, later spasticity; the term
“molar tooth” sign is used to describe the brainstem malformation with
elongated superior cerebellar peduncles and pronounced interpeduncular
fossa), the musculoskeletal system (postaxial polydactyly, slender
skeleton), the kidneys (multiple medullary cysts, renal impairment), and the
viscera (hepatomegaly splenomegaly, hepatic cirrhosis, and portal
hypertension in 70% of patients). Episodic tachypnea and ventricular
septal defect have been described. Death may result from complications of
hepatic fibrosis, gastrointestinal bleeding, or kidney failure. Successful liver and
combined liver and kidney transplantation have been reported.