Arima Syndrome

Description

Arima syndrome is an autosomal recessive disorder characterized by agenesis of the cerebellar vermis, ocular abnormalities, cystic kidney disease, and, in some cases, liver disease. It shares phenotypic features with Joubert syndrome (see 213300), COACH syndrome (216360), and familial juvenile nephronophthisis (see 256100).

Clinical Features

Dekaban (1969) reported 2 sibs with congenital retinal blindness (Leber), polycystic kidneys, and maldevelopment of the brain, including agenesis of the cerebellar vermis. Arima et al. (1971) reported 2 sibs and an unrelated girl with blindness, severe psychomotor retardation, hypotonia since early infancy, agenesis of the cerebellar vermis, and polycystic kidneys.

Matsuzaka et al. (1986) reported 3 unrelated patients, 2 boys and a girl, with severe visual impairment from early infancy, psychomotor retardation, hypotonia, nystagmus, blepharoptosis, and progressive chronic renal insufficiency. Postmortem examination of the 2 boys, who died at ages 12 and 13 years, showed almost total aplasia of the cerebellar vermis, malformations of the brainstem, including pachygyria of the inferior olivary nuclei and partial absence and anomalous position of the pyramidal tracts, and polycystic kidneys. One patient had hepatic steatosis and the other had hepatic fibrosis. Matsuzaka et al. (1986) concluded that the constellation of findings was consistent with a distinct clinicopathologic entity, which they termed 'cerebro-oculo-hepato-renal syndrome,' or 'Arima syndrome.'

Lindhout et al. (1980) reported a case of Joubert syndrome with associated bilateral chorioretinal coloboma, which the authors noted had not previously been reported in Joubert syndrome. Pfeiffer (1981) also reported Joubert syndrome associated with bilateral chorioretinal coloboma.

Saraiva and Baraitser (1992) suggested that patients with Joubert syndrome fall into 2 groups: those with retinal dystrophy and those without. They observed that retinal dystrophy ran true in families and was never absent when renal cysts were present. The renal cysts were multiple, small, and cortical; affected kidneys also had interstitial chronic inflammation and fibrosis. The histopathologic changes had not been reported in patients without retinal dystrophy. The conclusions were based on 72 previously reported cases and 29 new cases with the possible diagnosis of Joubert syndrome. Saraiva and Baraitser (1992) suggested that the form of Joubert syndrome with retinal dystrophy could be called Dekaban syndrome, since it was first reported by Dekaban (1969).

Ivarsson et al. (1993) described a boy with manifestations of Joubert syndrome, retinal dystrophy (which they referred to as Leber congenital amaurosis), and multicystic kidneys.

Lewis et al. (1994) described 2 unrelated children with Joubert syndrome and hepatosplenomegaly. On histopathologic examination, both had congenital hepatic fibrosis. Both were also found to have congenital medullary cystic disease of the kidneys. Lewis et al. (1994) suggested that Joubert syndrome is a member of a spectrum of congenital malformation syndromes involving the CNS, eye, liver, and kidneys. The authors noted phenotypic overlap with COACH syndrome.

Kumada et al. (2004) reported pathologic features of renal disease in 5 patients with Arima syndrome: 2 patients had been reported by Matsuzaka et al. (1986); 1 patient had been reported by Arima et al. (1971); and 1 patient, born of consanguineous parents, had been reported by Koya et al. (1973). Every patient developed end-stage renal disease during childhood, characterized primarily by renal sodium wasting and disturbances of urine concentration. The patients also had polyuria, polydipsia, anemia, and growth retardation. Grossly, the kidneys were small with granular capsular surfaces, and contained multiple cysts of various sizes throughout the organ. Histologic examination showed interstitial fibrosis, mononuclear cell infiltration, tubular atrophy with cyst formation, and accumulation of PAS-positive material around the tubules consistent with a thickened tubular basement membrane. Tubular cysts were predominantly located at the corticomedullary areas. Anatomical abnormalities of the ureters and bladder were not observed. Kumada et al. (2004) suggested that the renal disease in their patients with Arima syndrome was most consistent with nephronophthisis, and not cystic dysplastic kidney or infantile polycystic kidney. They emphasized the phenotypic overlap and diagnostic difficulties among Arima syndrome, Joubert syndrome, COACH syndrome, and some forms of familial nephronophthisis.

Diagnosis

Differential Diagnosis

Di Rocco (1993) suggested that 'Joubert syndrome with retinal dystrophy and renal cysts' may represent the carbohydrate-deficient glycoprotein syndrome (CDG; 212065). She further suggested that the CDG syndrome must be considered in any patient with cerebellar dysplasia and renal or liver abnormalities.

Prenatal Diagnosis

In a subsequent pregnancy of the mother of a child with Joubert syndrome and multicystic kidneys, Ivarsson et al. (1993) made the prenatal diagnosis on the basis of ultrasound, which demonstrated an occipital meningocele and multiple cysts of both kidneys, at 17 weeks of gestation.