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Infantile cerebellar-retinal degeneration(ICRD)

MedGen UID:
482822
Concept ID:
C3281192
Disease or Syndrome
Synonym: ICRD
SNOMED CT: Infantile cerebellar and retinal degeneration (782822006)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): ACO2 (22q13.2)
 
Monarch Initiative: MONDO:0013802
OMIM®: 614559
Orphanet: ORPHA313850

Definition

Infantile cerebellar-retinal degeneration (ICRD) is a severe autosomal recessive neurodegenerative disorder characterized by onset between ages 2 and 6 months of truncal hypotonia, athetosis, seizures, and ophthalmologic abnormalities, particularly optic atrophy and retinal degeneration. Affected individuals show profound psychomotor retardation, with only some achieving rolling, sitting, or recognition of family. Brain MRI shows progressive cerebral and cerebellar degeneration (summary by Spiegel et al., 2012). A subset of patients may have a milder phenotype with variable features, including ataxia, developmental delay, and behavioral abnormalities (Blackburn et al., 2020). Mutation in the ACO2 gene also causes isolated optic atrophy (OPA9; 616289). [from OMIM]

Clinical features

From HPO
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Decreased body weight
MedGen UID:
1806755
Concept ID:
C5574742
Finding
Abnormally low body weight.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Athetosis
MedGen UID:
2115
Concept ID:
C0004158
Disease or Syndrome
A slow, continuous, involuntary writhing movement that prevents maintenance of a stable posture. Athetosis involves continuous smooth movements that appear random and are not composed of recognizable sub-movements or movement fragments. In contrast to chorea, in athetosis, the same regions of the body are repeatedly involved. Athetosis may worsen with attempts at movement of posture, but athetosis can also occur at rest.
Cerebellar ataxia
MedGen UID:
849
Concept ID:
C0007758
Disease or Syndrome
Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Intellectual disability, severe
MedGen UID:
48638
Concept ID:
C0036857
Mental or Behavioral Dysfunction
Severe mental retardation is defined as an intelligence quotient (IQ) in the range of 20-34.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Demyelinating peripheral neuropathy
MedGen UID:
82859
Concept ID:
C0270922
Disease or Syndrome
Demyelinating neuropathy is characterized by slow nerve conduction velocities with reduced amplitudes of sensory/motor nerve conduction and prolonged distal latencies.
Hypoplasia of the corpus callosum
MedGen UID:
138005
Concept ID:
C0344482
Congenital Abnormality
Underdevelopment of the corpus callosum.
Bilateral tonic-clonic seizure
MedGen UID:
141670
Concept ID:
C0494475
Sign or Symptom
A bilateral tonic-clonic seizure is a seizure defined by a tonic (bilateral increased tone, lasting seconds to minutes) and then a clonic (bilateral sustained rhythmic jerking) phase.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Focal-onset seizure
MedGen UID:
199670
Concept ID:
C0751495
Disease or Syndrome
A focal-onset seizure is a type of seizure originating within networks limited to one hemisphere. They may be discretely localized or more widely distributed, and may originate in subcortical structures.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Severe global developmental delay
MedGen UID:
332436
Concept ID:
C1837397
Finding
A severe delay in the achievement of motor or mental milestones in the domains of development of a child.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Progressive microcephaly
MedGen UID:
340542
Concept ID:
C1850456
Anatomical Abnormality
Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Nystagmus
MedGen UID:
45166
Concept ID:
C0028738
Disease or Syndrome
Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.
Retinal dystrophy
MedGen UID:
208903
Concept ID:
C0854723
Finding
Retinal dystrophy is an abnormality of the retina associated with a hereditary process. Retinal dystrophies are defined by their predominantly monogenic inheritance and they are frequently associated with loss or dysfunction of photoreceptor cells as a primary or secondary event.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVInfantile cerebellar-retinal degeneration
Follow this link to review classifications for Infantile cerebellar-retinal degeneration in Orphanet.

Recent clinical studies

Diagnosis

Lail N, Pandey AK, Venkatesh S, Noland RD, Swanson G, Pain D, Branson HM, Suzuki CK, Yoon G
Neurology 2023 Oct 10;101(15):e1567-e1571. Epub 2023 Jul 17 doi: 10.1212/WNL.0000000000207649. PMID: 37460232Free PMC Article
Park JS, Kim MJ, Kim SY, Lim BC, Kim KJ, Seong MW, Lee JS, Chae JH
Brain Dev 2020 Oct;42(9):680-685. Epub 2020 Jul 24 doi: 10.1016/j.braindev.2020.07.003. PMID: 32713659
Sharkia R, Wierenga KJ, Kessel A, Azem A, Bertini E, Carrozzo R, Torraco A, Goffrini P, Ceccatelli Berti C, McCormick ME, Plecko B, Klein A, Abela L, Hengel H, Schöls L, Shalev S, Khayat M, Mahajnah M, Spiegel R
J Inherit Metab Dis 2019 Mar;42(2):264-275. Epub 2019 Jan 28 doi: 10.1002/jimd.12022. PMID: 30689204
Abela L, Spiegel R, Crowther LM, Klein A, Steindl K, Papuc SM, Joset P, Zehavi Y, Rauch A, Plecko B, Simmons TL
PLoS One 2017;12(5):e0176363. Epub 2017 May 2 doi: 10.1371/journal.pone.0176363. PMID: 28463998Free PMC Article
Sadat R, Barca E, Masand R, Donti TR, Naini A, De Vivo DC, DiMauro S, Hanchard NA, Graham BH
Mol Genet Metab 2016 May;118(1):28-34. Epub 2016 Mar 8 doi: 10.1016/j.ymgme.2016.03.004. PMID: 26992325Free PMC Article

Prognosis

Gibson S, Azamian MS, Lalani SR, Yen KG, Sutton VR, Scott DA
Am J Med Genet A 2020 Aug;182(8):1960-1966. Epub 2020 May 25 doi: 10.1002/ajmg.a.61634. PMID: 32449285
Sharkia R, Wierenga KJ, Kessel A, Azem A, Bertini E, Carrozzo R, Torraco A, Goffrini P, Ceccatelli Berti C, McCormick ME, Plecko B, Klein A, Abela L, Hengel H, Schöls L, Shalev S, Khayat M, Mahajnah M, Spiegel R
J Inherit Metab Dis 2019 Mar;42(2):264-275. Epub 2019 Jan 28 doi: 10.1002/jimd.12022. PMID: 30689204
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
Am J Hum Genet 2012 Mar 9;90(3):518-23. doi: 10.1016/j.ajhg.2012.01.009. PMID: 22405087Free PMC Article

Clinical prediction guides

Gibson S, Azamian MS, Lalani SR, Yen KG, Sutton VR, Scott DA
Am J Med Genet A 2020 Aug;182(8):1960-1966. Epub 2020 May 25 doi: 10.1002/ajmg.a.61634. PMID: 32449285
Sharkia R, Wierenga KJ, Kessel A, Azem A, Bertini E, Carrozzo R, Torraco A, Goffrini P, Ceccatelli Berti C, McCormick ME, Plecko B, Klein A, Abela L, Hengel H, Schöls L, Shalev S, Khayat M, Mahajnah M, Spiegel R
J Inherit Metab Dis 2019 Mar;42(2):264-275. Epub 2019 Jan 28 doi: 10.1002/jimd.12022. PMID: 30689204
Sadat R, Barca E, Masand R, Donti TR, Naini A, De Vivo DC, DiMauro S, Hanchard NA, Graham BH
Mol Genet Metab 2016 May;118(1):28-34. Epub 2016 Mar 8 doi: 10.1016/j.ymgme.2016.03.004. PMID: 26992325Free PMC Article

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