An inherited syndrome characterized by the combination
of hepatic fibrosis, early onset ataxia, cerebellar aplasia, oligophrenia,
and coloboma. COACH is an acronym for cerebellar vermis aplasia,
oligophrenia, congenital ataxia, ocular coloboma and hepatic fibrosis.
Fewer than 20 cases have been
described. Autosomal recessive inheritance. Parental consanguinity has been
reported in some cases.
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.
Obtain a complete blood count (anemia
secondary to gastrointestinal hemorrhage) and check serum levels of
electrolytes. Thrombocytopenia secondary to portal hypertension with splenomegaly
(hypersplenism) was described in one patient. Assess renal (creatinine, blood urea nitrogen) and hepatic
function (transaminases, bilirubin, albumin, coagulation status).
Reduced doses of muscle relaxant agents may be required. Consider alterations in the metabolism and
elimination of drugs in the presence of hepatic and/or renal failure. The
potential for airway obstruction, a result of macroglossia, requires
preoperative evaluation. Careful insertion of nasogastric tubes is required
because the majority of patients have esophageal varices. Bleeding from
abdominal surgery may be increased in the presence of portal hypertension
and coagulopathy. Large-bore intravenous access is therefore recommended. Consider subacute bacterial endocarditis prophylaxis in
the presence of congenital cardiac lesions.
Joubert Syndrome: A genetic peroxisomal disorder characterized by
cerebral malformations (vermis and brainstem) resulting in severe
coordination (ataxia) and breathing (sleep apnea, hyperpnea) disorders.
Arima Syndrome (Cerebro-Oculo-Hepato-Renal Syndrome): This syndrome is
similar to Joubert syndrome, however, the Arima syndrome also presents with
retinal dystrophy and visual tracking anomalies (oculomotor ataxia), renal
failure, and liver dysfunction.
Loken Senior Syndrome: An autosomal recessive inherited disorder
characterized by rapidly progressive renal insufficiency (nephronophthisis),
progressive retinitis pigmentosa, and ataxia. Manifestation during
the first year of life. Blindness develops within the first 2 years of life.
Renal-Coloboma Syndrome: A familial syndrome combining ocular, renal,
and neurologic anomalies.
Foell D, August C, Frosch M, et al: Early ...