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Microcephaly 23, primary, autosomal recessive(MCPH23)

MedGen UID:
1631589
•Concept ID:
C4693843
•
Disease or Syndrome
Synonyms: MCPH23; MICROCEPHALY 23, PRIMARY, AUTOSOMAL RECESSIVE
 
Gene (location): NCAPH (2q11.2)
 
Monarch Initiative: MONDO:0054806
OMIM®: 617985

Clinical features

From HPO
Small for gestational age
MedGen UID:
65920
•Concept ID:
C0235991
•
Finding
Smaller than normal size according to sex and gestational age related norms, defined as a weight below the 10th percentile for the gestational age.
See: Feature record | Search on this feature
Intellectual disability, moderate
MedGen UID:
7680
•Concept ID:
C0026351
•
Mental or Behavioral Dysfunction
Moderate mental retardation is defined as an intelligence quotient (IQ) in the range of 35-49.
See: Feature record | Search on this feature
Microcephaly
MedGen UID:
1644158
•Concept ID:
C4551563
•
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
See: Feature record | Search on this feature
Sloping forehead
MedGen UID:
346640
•Concept ID:
C1857679
•
Finding
Inclination of the anterior surface of the forehead from the vertical more than two standard deviations above the mean (objective); or apparently excessive posterior sloping of the forehead in a lateral view.
See: Feature record | Search on this feature
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Recent clinical studies

Etiology

Insulin response dysregulation explains abnormal fat storage and increased risk of diabetes mellitus type 2 in Cohen Syndrome.
Limoge F, Faivre L, Gautier T, Petit JM, Gautier E, Masson D, Jego G, El Chehadeh-Djebbar S, Marle N, Carmignac V, Deckert V, Brindisi MC, Edery P, Ghoumid J, Blair E, Lagrost L, Thauvin-Robinet C, Duplomb L
Hum Mol Genet 2015 Dec 1;24(23):6603-13. Epub 2015 Sep 10 doi: 10.1093/hmg/ddv366. PMID: 26358774
The molecular landscape of ASPM mutations in primary microcephaly.
Nicholas AK, Swanson EA, Cox JJ, Karbani G, Malik S, Springell K, Hampshire D, Ahmed M, Bond J, Di Benedetto D, Fichera M, Romano C, Dobyns WB, Woods CG
J Med Genet 2009 Apr;46(4):249-53. Epub 2008 Nov 21 doi: 10.1136/jmg.2008.062380. PMID: 19028728Free PMC Article

Diagnosis

Molecular analysis of 23 Pakistani families with autosomal recessive primary microcephaly using targeted next-generation sequencing.
Wang R, Khan A, Han S, Zhang X
J Hum Genet 2017 Feb;62(2):299-304. Epub 2016 Oct 27 doi: 10.1038/jhg.2016.128. PMID: 27784895
Insulin response dysregulation explains abnormal fat storage and increased risk of diabetes mellitus type 2 in Cohen Syndrome.
Limoge F, Faivre L, Gautier T, Petit JM, Gautier E, Masson D, Jego G, El Chehadeh-Djebbar S, Marle N, Carmignac V, Deckert V, Brindisi MC, Edery P, Ghoumid J, Blair E, Lagrost L, Thauvin-Robinet C, Duplomb L
Hum Mol Genet 2015 Dec 1;24(23):6603-13. Epub 2015 Sep 10 doi: 10.1093/hmg/ddv366. PMID: 26358774
Misregulation of mitotic chromosome segregation in a new type of autosomal recessive primary microcephaly.
Marchal JA, Ghani M, Schindler D, Gavvovidis I, Winkler T, Esquitino V, Sternberg N, Busche A, Krawitz P, Hecht J, Robinson P, Mundlos S, Graul-Neumann L, Sperling K, Trimborn M, Neitzel H
Cell Cycle 2011 Sep 1;10(17):2967-77. doi: 10.4161/cc.10.17.16871. PMID: 21857152
The molecular landscape of ASPM mutations in primary microcephaly.
Nicholas AK, Swanson EA, Cox JJ, Karbani G, Malik S, Springell K, Hampshire D, Ahmed M, Bond J, Di Benedetto D, Fichera M, Romano C, Dobyns WB, Woods CG
J Med Genet 2009 Apr;46(4):249-53. Epub 2008 Nov 21 doi: 10.1136/jmg.2008.062380. PMID: 19028728Free PMC Article
Cockayne's syndrome: a case report. Literature review.
Arenas-Sordo Mde L, Hernández-Zamora E, Montoya-Pérez LA, Aldape-Barrios BC
Med Oral Patol Oral Cir Bucal 2006 May 1;11(3):E236-8. PMID: 16648759

Prognosis

A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly.
Fellows BJ, Tolezano GC, Pires SF, Ruegg MSG, Knapp KM, Krepischi ACV, Bicknell LS
Am J Med Genet A 2024 Mar;194(3):e63468. Epub 2023 Nov 8 doi: 10.1002/ajmg.a.63468. PMID: 37937525
Protein-truncating mutations in ASPM cause variable reduction in brain size.
Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, Mochida GH, Hennekam RC, Maher ER, Fryns JP, Alswaid A, Jafri H, Rashid Y, Mubaidin A, Walsh CA, Roberts E, Woods CG
Am J Hum Genet 2003 Nov;73(5):1170-7. Epub 2003 Oct 21 doi: 10.1086/379085. PMID: 14574646Free PMC Article

Clinical prediction guides

A novel KNL1 intronic splicing variant likely destabilizes the KMN complex, causing primary microcephaly.
Fellows BJ, Tolezano GC, Pires SF, Ruegg MSG, Knapp KM, Krepischi ACV, Bicknell LS
Am J Med Genet A 2024 Mar;194(3):e63468. Epub 2023 Nov 8 doi: 10.1002/ajmg.a.63468. PMID: 37937525
CDK5RAP2 interaction with components of the Hippo signaling pathway may play a role in primary microcephaly.
Sukumaran SK, Stumpf M, Salamon S, Ahmad I, Bhattacharya K, Fischer S, Müller R, Altmüller J, Budde B, Thiele H, Tariq M, Malik NA, Nürnberg P, Baig SM, Hussain MS, Noegel AA
Mol Genet Genomics 2017 Apr;292(2):365-383. Epub 2016 Dec 21 doi: 10.1007/s00438-016-1277-x. PMID: 28004182Free PMC Article
Misregulation of mitotic chromosome segregation in a new type of autosomal recessive primary microcephaly.
Marchal JA, Ghani M, Schindler D, Gavvovidis I, Winkler T, Esquitino V, Sternberg N, Busche A, Krawitz P, Hecht J, Robinson P, Mundlos S, Graul-Neumann L, Sperling K, Trimborn M, Neitzel H
Cell Cycle 2011 Sep 1;10(17):2967-77. doi: 10.4161/cc.10.17.16871. PMID: 21857152
Cockayne's syndrome: a case report. Literature review.
Arenas-Sordo Mde L, Hernández-Zamora E, Montoya-Pérez LA, Aldape-Barrios BC
Med Oral Patol Oral Cir Bucal 2006 May 1;11(3):E236-8. PMID: 16648759
Protein-truncating mutations in ASPM cause variable reduction in brain size.
Bond J, Scott S, Hampshire DJ, Springell K, Corry P, Abramowicz MJ, Mochida GH, Hennekam RC, Maher ER, Fryns JP, Alswaid A, Jafri H, Rashid Y, Mubaidin A, Walsh CA, Roberts E, Woods CG
Am J Hum Genet 2003 Nov;73(5):1170-7. Epub 2003 Oct 21 doi: 10.1086/379085. PMID: 14574646Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • Gene
      Related information in NCBI Gene
    • GTR
      Related information in GTR
    • GTR(Clinical)
      Clinical tests in GTR
    • OMIM
      Related records in OMIM
    • OMIM(Genes)
      OMIM records containing genes associated with phenotypes registered in MedGen
    • PubMed (OMIM)
      Related literature resources in PubMed

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