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Disease Profile

Infantile cerebellar retinal degeneration

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Infantile cerebellar-retinal degeneration; ICRD

Categories

Congenital and Genetic Diseases; Eye diseases; Nervous System Diseases

Summary

Infantile cerebellar retinal degeneration (ICRD) is a genetic condition present from birth (congenital) that involves the brain and eyes.[1][2] Individuals with this condition usually develop symptoms around six months of age including developmental delays, low muscle tone (hypotonia), and seizures. Other symptoms may include head bobbing, abnormal muscle twitching and movement, and loss of brain cells in the main part of the brain called the cerebellum. Eye findings in individuals with this condition may include retinal degeneration (weakening of the layer of tissue in the back of the eye that senses light), strabismus (crossed eyes), and nystagmus (fast, uncontrollable movements of the eyes).[1][2][3] ICRD is caused by mutations in the ACO2 gene and is inherited in an autosomal recessive manner.[4] While there is still no cure for this condition, treatment options will depend on the type and severity of symptoms.

Symptoms

The signs and symptoms of ICRD usually begin around 2-6 months of age. The main feature of this condition involve a decline of the ophthalmologic and nervous systems and may include:[1][4]

  • Developmental delay and intellectual disability
  • Weakness (hypotonia) of the muscles in the chest and abdomen
  • Slow, involuntary movement of certain muscles in the body (athetosis)
  • Seizures
  • Head bobbing
  • Retinal degeneration
  • Eye abnormalities such as strabismus and nystagmus
  • Failure to thrive (slow or inadequate weight gain) 
  • Hearing and vision loss
  • Absence or loss of reflexes 

On brain imaging such as MRI, findings may include worsening cerebellar atrophy as well as agenesis of the corpus callosum. Additionally, the head of individuals with ICRD may not grow at the same rate as the rest of the body, so it appears to be getting smaller than the rest of the body (progressive microcephaly).[1][4]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
5%-29% of people have these symptoms
Sensorineural hearing impairment
0000407
Percent of people who have these symptoms is not available through HPO
Areflexia
Absent tendon reflexes
0001284
Ataxia
0001251
Athetosis
Involuntary writhing movements in fingers, hands, toes, and feet
0002305
Autosomal recessive inheritance
0000007
Cerebellar atrophy
Degeneration of cerebellum
0001272
Cerebral cortical atrophy
Decrease in size of the outer layer of the brain due to loss of brain cells
0002120
Demyelinating peripheral neuropathy
0007108
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Intellectual disability, severe
Early and severe mental retardation
Mental retardation, severe
Severe mental retardation

[ more ]

0010864
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Optic atrophy
0000648
Progressive microcephaly
Progressively abnormally small cranium
Progressively abnormally small skull

[ more ]

0000253
Retinal dystrophy
Breakdown of light-sensitive cells in back of eye
0000556
Seizure
0001250
Severe global developmental delay
0011344
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486

Cause

ICRD is a genetic disorder caused by mutations in the ACO2 gene. This gene codes for a protein found in the mitochondria that is involved in the citric acid cycle, which is the process in which energy is created from the breakdown of the foods we eat.[5]

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

References

  1. Spiegel R, Pines O, Ta-Shma A, et al. Infantile Cerebellar-Retinal Degeneration Associated with a Mutation in Mitochondrial Aconitase, ACO2. American Journal of Human Genetics. March 9, 2012; 90(3):518-523. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3309186/.
  2. Infantile Cerebellar-Retinal Degeneration. The University of Arizona Health Sciences Hereditary Ocular Disease Database. https://disorders.eyes.arizona.edu/disorders/infantile-cerebellar-retinal-degeneration. Accessed 4/26/2017.
  3. Bird TD. Hereditary Ataxia Overview. GeneReviews. November 3, 2016; https://www.ncbi.nlm.nih.gov/books/NBK1138/.
  4. Kniffen CL. Infantile Cerebellar-Retinal Degeneration; ICRD. Online Mendelian Inheritance in Man (OMIM). 4/2/2015; https://omim.org/entry/614559.
  5. ACO2 aconitase 2 [ Homo sapiens (human) ]. National Center for Biotechnology Information (NCBI). April 20, 2017; https://www.ncbi.nlm.nih.gov/gene/50.

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