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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): Gene(s) directly associated with this condition or phenotype.	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.

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Microcephaly

MedGen UID:: 1644158
•Concept ID:: C4551563
•: Finding

Head circumference below 2 standard deviations below the mean for age and gender.

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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.

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Abnormality of head or neck
- Sloping forehead
Abnormality of the musculoskeletal system
- Microcephaly
Abnormality of the nervous system
- Intellectual disability, moderate
Growth abnormality
- Small for gestational age

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: 19028728 Free PMC Article

See all (2)

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.

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.

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

See all (5)

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: 14574646 Free PMC Article

See all (2)

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: 28004182 Free PMC Article

Misregulation of mitotic chromosome segregation in a new type of autosomal recessive primary microcephaly.

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.

See all (5)