Microcephaly 2, Primary, Autosomal Recessive, with or without Cortical Malformations

Alternative Names

  • MCPH2
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WHO-ICD-10 version:2010

Congenital malformations, deformations and chromosomal abnormalities

Congenital malformations of the nervous system

OMIM Number

604317

Mode of Inheritance

Autosomal recessive

Gene Map Locus

19q13.12

Description

Primary Microcephaly is defined as having a head circumference at least 2 SD below the mean for age, sex, and ethnicity.  MCPH2 is an autosomal recessive condition characterized by primary microcephaly, mental retardation, and no other associated malformations.  Typically, the patients have low, sloping foreheads.  Patients usually, but not necessarily, show cortical malformations on neural scans.  These malformations include polymicrogyria, pachygyria, hypoplasia of corpus callosum, abnormal/simplified gyral patterning and lissencephaly.  Patients show abnormal neurological and behavioural manifestations, including delayed psychomotor development, moderate to severe mental retardation, impulsivity, and aggression. 

Management of the condition centres mainly on supportive therapy, such as special education, speech and language therapy, behavioral therapy, occupational therapy, and community services for families.

Molecular Genetics

Most primary microcephalic conditions are associated with mutations in genes involved in basic cellular processes, such as cell division, and control of DNA integrity.  MCPH2 is caused by mutations in the WDR62 gene.  This gene codes for a protein product that regulates spindle orientation, centrosome integrity, and progression through mitosis.

Epidemiology in the Arab World

View Map
Subject IDCountrySexFamily HistoryParental ConsanguinityHPO TermsVariantZygosityMode of InheritanceReferenceRemarks
604317.1Saudi ArabiaMaleNoYes Lissencephaly; Colpocephaly; Spasticity;...NM_001083961.2:c.3012_3034dupHomozygousAutosomal, RecessiveShaheen et al. 2019
604317.2.1Saudi ArabiaMaleYesYes Pachygyria; Intellectual disability; Str...NM_001083961.2:c.193G>AHomozygousAutosomal, RecessiveShaheen et al. 2019

Other Reports

Sudan

Bastaki et al. (2015) reported a Sudanese family with MCPH2 with a novel mutation in the WDR62 gene.  The parents were consanguineous and were phenotypically normal.  The proband was a 11-year old boy who had been found to be microcephalic at birth (OFC-29.5cm).  Psychomotor development was delayed, as were fine motor skills.  Head circumference continued to stay below the 3rd centile.  MRI Brain showed complete lissencephaly.  His sister, aged 9-years, had a similar clinical presentation with developmental delay and microcephaly with incomplete lissencephaly.  In addition, she developed seizures at the age of 4-years and was on medication.  Her brain scan showed mild symmetrical widening of supra and infratentorial cerebral ventricles with no deformity or mildline shift, shallow sparse cortical sulci, with an overall appearance of smooth brain surface, prominent Sylvian fissures and extra axial CSF spaces.  Whole exome sequencing identified a homozygous variant in the WDR62 gene in both affected siblings.

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