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Microcephaly 4, primary, autosomal recessive(MCPH4)

MedGen UID:
347655
Concept ID:
C1858516
Disease or Syndrome
Synonym: Microcephaly, Primary Autosomal Recessive, 4
 
KNL1 (15q15.1)
 
Monarch Initiative: MONDO:0011437
OMIM®: 604321

Definition

Primary microcephaly (MCPH) is a clinical diagnosis made when an individual has a head circumference more than 3 standard deviations below the age- and sex-matched population mean and mental retardation, with no other associated malformations and with no apparent etiology. Most cases of primary microcephaly show an autosomal recessive mode of inheritance (summary by Woods et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of primary microcephaly, see MCPH1 (251200). [from OMIM]

Additional description

From MedlinePlus Genetics
Autosomal recessive primary microcephaly (often shortened to MCPH, which stands for "microcephaly primary hereditary") is a condition in which infants are born with a very small head and a small brain. The term "microcephaly" comes from the Greek words for "small head."

MCPH causes intellectual disability, which is typically mild to moderate and does not become more severe with age. Most affected individuals have delayed speech and language skills. Motor skills, such as sitting, standing, and walking, may also be mildly delayed.

Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. Head circumference is the distance around the widest part of the head, measured by placing a measuring tape above the eyebrows and ears and around the back of the head. Affected infants' brain volume is also smaller than usual, although they usually do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but they continue to be much smaller than normal.

People with MCPH usually have few or no other features associated with the condition. Some have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature compared to others in their family. The condition typically does not affect any other major organ systems or cause other health problems.  https://medlineplus.gov/genetics/condition/autosomal-recessive-primary-microcephaly

Clinical features

From HPO

Professional guidelines

PubMed

Seeman P, Gebertová K, Paderová K, Sperling K, Seemanová E
Pediatr Neurol 2004 Mar;30(3):195-200. doi: 10.1016/j.pediatrneurol.2003.07.003. PMID: 15033202

Recent clinical studies

Etiology

Spiegel R, Schwahn BC, Squires L, Confer N
J Inherit Metab Dis 2022 May;45(3):456-469. Epub 2022 Mar 3 doi: 10.1002/jimd.12488. PMID: 35192225Free PMC Article
Nasser H, Vera L, Elmaleh-Bergès M, Steindl K, Letard P, Teissier N, Ernault A, Guimiot F, Afenjar A, Moutard ML, Héron D, Alembik Y, Momtchilova M, Milani P, Kubis N, Pouvreau N, Zollino M, Guilmin Crepon S, Kaguelidou F, Gressens P, Verloes A, Rauch A, El Ghouzzi V, Drunat S, Passemard S
J Med Genet 2020 Jun;57(6):389-399. Epub 2020 Feb 3 doi: 10.1136/jmedgenet-2019-106474. PMID: 32015000
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
Bracha HS
Prog Neuropsychopharmacol Biol Psychiatry 2006 Jul;30(5):827-53. Epub 2006 Mar 23 doi: 10.1016/j.pnpbp.2006.01.008. PMID: 16563589Free PMC Article
Seeman P, Gebertová K, Paderová K, Sperling K, Seemanová E
Pediatr Neurol 2004 Mar;30(3):195-200. doi: 10.1016/j.pediatrneurol.2003.07.003. PMID: 15033202

Diagnosis

Karla AR, Pinard A, Boerio ML, Hemelsoet D, Tavernier SJ, De Pauw M, Vereecke E, Fraser S, Bamshad MJ, Guo D, Callewaert B, Milewicz DM
Am J Med Genet A 2024 Apr;194(4):e63486. Epub 2023 Dec 1 doi: 10.1002/ajmg.a.63486. PMID: 38041217Free PMC Article
Gönenc II, Elcioglu NH, Martinez Grijalva C, Aras S, Großmann N, Praulich I, Altmüller J, Kaulfuß S, Li Y, Nürnberg P, Burfeind P, Yigit G, Wollnik B
Clin Genet 2022 May;101(5-6):559-564. Epub 2022 Mar 11 doi: 10.1111/cge.14125. PMID: 35218564
Spiegel R, Schwahn BC, Squires L, Confer N
J Inherit Metab Dis 2022 May;45(3):456-469. Epub 2022 Mar 3 doi: 10.1002/jimd.12488. PMID: 35192225Free PMC Article
Kalmin MM, Gower EW, Stringer EM, Bowman NM, Rogawski McQuade ET, Westreich D
Paediatr Perinat Epidemiol 2019 Jul;33(4):286-290. doi: 10.1111/ppe.12561. PMID: 31347726Free PMC Article
Mahmood S, Ahmad W, Hassan MJ
Orphanet J Rare Dis 2011 Jun 13;6:39. doi: 10.1186/1750-1172-6-39. PMID: 21668957Free PMC Article

Therapy

Nasser H, Vera L, Elmaleh-Bergès M, Steindl K, Letard P, Teissier N, Ernault A, Guimiot F, Afenjar A, Moutard ML, Héron D, Alembik Y, Momtchilova M, Milani P, Kubis N, Pouvreau N, Zollino M, Guilmin Crepon S, Kaguelidou F, Gressens P, Verloes A, Rauch A, El Ghouzzi V, Drunat S, Passemard S
J Med Genet 2020 Jun;57(6):389-399. Epub 2020 Feb 3 doi: 10.1136/jmedgenet-2019-106474. PMID: 32015000
Kitagawa D, Kohlmaier G, Keller D, Strnad P, Balestra FR, Flückiger I, Gönczy P
J Cell Sci 2011 Nov 15;124(Pt 22):3884-93. Epub 2011 Nov 18 doi: 10.1242/jcs.089888. PMID: 22100914

Prognosis

Batool T, Irshad S, Riaz M, Mahmood Baig S, Nuernberg P, Hussain MS
J Hum Genet 2023 Jul;68(7):469-475. Epub 2023 Mar 3 doi: 10.1038/s10038-023-01132-6. PMID: 36864288
Spiegel R, Schwahn BC, Squires L, Confer N
J Inherit Metab Dis 2022 May;45(3):456-469. Epub 2022 Mar 3 doi: 10.1002/jimd.12488. PMID: 35192225Free PMC Article
Tavasoli AR, Memar EHE, Ashrafi MR, Hosseini SMM, Haghighi R, Ghabeli H, Pourbakhtyaran E, Rasoulinezhad M, Mohammadi P, Heidari M
J Mol Neurosci 2022 Apr;72(4):719-729. Epub 2022 Jan 4 doi: 10.1007/s12031-021-01955-y. PMID: 34982360
Batool T, Irshad S, Mahmood K
Braz J Biol 2021;83:e246040. Epub 2021 Aug 6 doi: 10.1590/1519-6984.246040. PMID: 34378666
Kalmin MM, Gower EW, Stringer EM, Bowman NM, Rogawski McQuade ET, Westreich D
Paediatr Perinat Epidemiol 2019 Jul;33(4):286-290. doi: 10.1111/ppe.12561. PMID: 31347726Free PMC Article

Clinical prediction guides

Batool T, Irshad S, Riaz M, Mahmood Baig S, Nuernberg P, Hussain MS
J Hum Genet 2023 Jul;68(7):469-475. Epub 2023 Mar 3 doi: 10.1038/s10038-023-01132-6. PMID: 36864288
Gönenc II, Elcioglu NH, Martinez Grijalva C, Aras S, Großmann N, Praulich I, Altmüller J, Kaulfuß S, Li Y, Nürnberg P, Burfeind P, Yigit G, Wollnik B
Clin Genet 2022 May;101(5-6):559-564. Epub 2022 Mar 11 doi: 10.1111/cge.14125. PMID: 35218564
Kalmin MM, Gower EW, Stringer EM, Bowman NM, Rogawski McQuade ET, Westreich D
Paediatr Perinat Epidemiol 2019 Jul;33(4):286-290. doi: 10.1111/ppe.12561. PMID: 31347726Free PMC Article
Rosin N, Elcioglu NH, Beleggia F, Isgüven P, Altmüller J, Thiele H, Steindl K, Joset P, Rauch A, Nürnberg P, Wollnik B, Yigit G
Hum Mol Genet 2015 Jul 1;24(13):3708-17. Epub 2015 Apr 3 doi: 10.1093/hmg/ddv115. PMID: 25839420
Passemard S, Titomanlio L, Elmaleh M, Afenjar A, Alessandri JL, Andria G, de Villemeur TB, Boespflug-Tanguy O, Burglen L, Del Giudice E, Guimiot F, Hyon C, Isidor B, Mégarbané A, Moog U, Odent S, Hernandez K, Pouvreau N, Scala I, Schaer M, Gressens P, Gerard B, Verloes A
Neurology 2009 Sep 22;73(12):962-9. doi: 10.1212/WNL.0b013e3181b8799a. PMID: 19770472

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