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Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly

MedGen UID:
462271
Concept ID:
C3150921
Disease or Syndrome
Synonym: Microcephaly, postnatal progressive, with seizures and brain atrophy
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): MED17 (11q21)
 
Monarch Initiative: MONDO:0013351
OMIM®: 613668
Orphanet: ORPHA402364

Definition

Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly is a rare, central nervous system malformation syndrome characterized by progressive microcephaly with profound motor delay and intellectual disability, associated with hypertonia, spasticity, clonus, and seizures, with brain imaging revealing severe cerebral and cerebellar atrophy, and poor myelination. [from ORDO]

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.
Dysphagia
MedGen UID:
41440
Concept ID:
C0011168
Disease or Syndrome
Difficulty in swallowing.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Clonus
MedGen UID:
40341
Concept ID:
C0009024
Sign or Symptom
A series of rhythmic and involuntary muscle contractions (at a frequency of about 5 to 7 Hz) that occur in response to an abruptly applied and sustained stretch.
Spasticity
MedGen UID:
7753
Concept ID:
C0026838
Sign or Symptom
A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Diffuse cerebral atrophy
MedGen UID:
108958
Concept ID:
C0598275
Finding
Diffuse unlocalised atrophy affecting the cerebrum.
Hypsarrhythmia
MedGen UID:
195766
Concept ID:
C0684276
Finding
Hypsarrhythmia is abnormal interictal high amplitude waves and a background of irregular spikes. There is continuous (during wakefulness), high-amplitude (>200 Hz), generalized polymorphic slowing with no organized background and multifocal spikes demonstrated by electroencephalography (EEG).
Hypoplasia of the brainstem
MedGen UID:
334226
Concept ID:
C1842688
Finding
Underdevelopment of the brainstem.
Delayed CNS myelination
MedGen UID:
867393
Concept ID:
C4021758
Anatomical Abnormality
Delayed myelination in the central nervous system.
Decreased thalamic volume
MedGen UID:
868377
Concept ID:
C4022771
Finding
A reduction in the quantity of space occupied by the thalamus.
Hypertonia
MedGen UID:
10132
Concept ID:
C0026826
Finding
A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Secondary microcephaly
MedGen UID:
608952
Concept ID:
C0431352
Finding
Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVInfantile cerebral and cerebellar atrophy with postnatal progressive microcephaly
Follow this link to review classifications for Infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly in Orphanet.

Recent clinical studies

Diagnosis

Yin X, Tang B, Mao X, Peng J, Zeng S, Wang Y, Jiang H, Li N
J Hum Genet 2018 Sep;63(9):971-980. Epub 2018 Jun 18 doi: 10.1038/s10038-018-0478-z. PMID: 29915213
Nahorski MS, Asai M, Wakeling E, Parker A, Asai N, Canham N, Holder SE, Chen YC, Dyer J, Brady AF, Takahashi M, Woods CG
Brain 2016 Apr;139(Pt 4):1036-44. Epub 2016 Feb 25 doi: 10.1093/brain/aww014. PMID: 26917597Free PMC Article

Therapy

Yin X, Tang B, Mao X, Peng J, Zeng S, Wang Y, Jiang H, Li N
J Hum Genet 2018 Sep;63(9):971-980. Epub 2018 Jun 18 doi: 10.1038/s10038-018-0478-z. PMID: 29915213

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