Infantile Cerebellar-Retinal Degeneration

Clinical Characteristics

Ocular Features:

Visual tracking can be normal during the newborn period but lack of visual fixation and attention soon become evident. Strabismus, nystagmus, and abnormal pursuit movements are often present. Optic atrophy has been reported as early as 3 years of age. VEP and ERG responses are extinguished in the first two years. The nystagmus may be multidirectional. Acuity loss seems to be progressive. A progressive retinal degeneration (not further characterized) has been reported.

Systemic Features:

Infants generally appear normal at birth. Within the first 6 months they show signs of developmental delay and neurological signs such as truncal hypotonia, seizures, athetosis and head bobbing. Milestones of sitting, rolling over, and reactions to others are seldom achieved. Cerebellar brain imaging shows progressive atrophy in all patients and some have cortical atrophy as well. Some patients have evidence of hearing loss. Severe failure to thrive and psychomotor delays are usually present. Death may occur within several months of birth although some live for several decades.

Genetics

This condition results from homozygous or compound heterozygous mutations in the ACO2 [1] gene (22q13.2). The mutation has also been associated with optic atrophy 9 [2] (616289 [3]).

Treatment

Treatment Options:

No treatment beyond supportive care is known.

References

Article Title:

Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause either isolated or syndromic optic neuropathy with encephalopathy and cerebellar atrophy [4]

Metodiev MD, Gerber S, Hubert L, Delahodde A, Chretien D, Gerard X, Amati-Bonneau P, Giacomotto MC, Boddaert N, Kaminska A, Desguerre I, Amiel J, Rio M, Kaplan J, Munnich A, Rotig A, Rozet JM, Besmond C. Mutations in the tricarboxylic acid cycle enzyme, aconitase 2, cause either isolated or syndromic optic neuropathy with encephalopathy and cerebellar atrophy. J Med Genet. 2014 Dec;51(12):834-8.

PubMed ID:

25351951

Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2 [5]

Spiegel R, Pines O, Ta-Shma A, Burak E, Shaag A, Halvardson J, Edvardson S, Mahajna M, Zenvirt S, Saada A, Shalev S, Feuk L, Elpeleg O. Infantile cerebellar-retinal degeneration associated with a mutation in mitochondrial aconitase, ACO2. Am J Hum Genet. 2012 Mar 9;90(3):518-23.

PubMed ID:

22405087