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Microcephaly 6, primary, autosomal recessive(MCPH6)

MedGen UID:
330770
Concept ID:
C1842109
Disease or Syndrome
Synonym: Microcephaly, Primary Autosomal Recessive, 6
 
Gene (location): CENPJ (13q12.12-12.13)
 
Monarch Initiative: MONDO:0012029
OMIM®: 608393

Definition

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.

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.

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.

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." [from MedlinePlus Genetics]

Clinical features

From HPO
Microtia
MedGen UID:
57535
Concept ID:
C0152423
Congenital Abnormality
Underdevelopment of the external ear.
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.
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.
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.
Small cerebral cortex
MedGen UID:
325187
Concept ID:
C1837503
Finding
Reduced size of the cerebral cortex.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Bifid nasal tip
MedGen UID:
140870
Concept ID:
C0426428
Finding
A splitting of the nasal tip. Visually assessable vertical indentation, cleft, or depression of the nasal tip.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
A misalignment of the eyes so that the visual axes deviate from bifoveal fixation. The classification of strabismus may be based on a number of features including the relative position of the eyes, whether the deviation is latent or manifest, intermittent or constant, concomitant or otherwise and according to the age of onset and the relevance of any associated refractive error.

Recent clinical studies

Etiology

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
Zombor M, Kalmár T, Nagy N, Berényi M, Telcs B, Maróti Z, Brandau O, Sztriha L
J Appl Genet 2019 May;60(2):151-162. Epub 2019 Feb 1 doi: 10.1007/s13353-019-00486-y. PMID: 30706430
Lin PY, Tseng MH, Zenker M, Rao J, Hildebrandt F, Lin SH, Lin CC, Chang JH, Hsu CH, Lee MD, Lin SP, Tsai JD
Orphanet J Rare Dis 2018 Dec 17;13(1):226. doi: 10.1186/s13023-018-0961-9. PMID: 30558655Free PMC Article
Létard P, Drunat S, Vial Y, Duerinckx S, Ernault A, Amram D, Arpin S, Bertoli M, Busa T, Ceulemans B, Desir J, Doco-Fenzy M, Elalaoui SC, Devriendt K, Faivre L, Francannet C, Geneviève D, Gérard M, Gitiaux C, Julia S, Lebon S, Lubala T, Mathieu-Dramard M, Maurey H, Metreau J, Nasserereddine S, Nizon M, Pierquin G, Pouvreau N, Rivier-Ringenbach C, Rossi M, Schaefer E, Sefiani A, Sigaudy S, Sznajer Y, Tunca Y, Guilmin Crepon S, Alberti C, Elmaleh-Bergès M, Benzacken B, Wollnick B, Woods CG, Rauch A, Abramowicz M, El Ghouzzi V, Gressens P, Verloes A, Passemard S
Hum Mutat 2018 Mar;39(3):319-332. Epub 2018 Jan 16 doi: 10.1002/humu.23381. PMID: 29243349
Putoux A, Alqahtani A, Pinson L, Paulussen AD, Michel J, Besson A, Mazoyer S, Borg I, Nampoothiri S, Vasiljevic A, Uwineza A, Boggio D, Champion F, de Die-Smulders CE, Gardeitchik T, van Putten WK, Perez MJ, Musizzano Y, Razavi F, Drunat S, Verloes A, Hennekam R, Guibaud L, Alix E, Sanlaville D, Lesca G, Edery P
Clin Genet 2016 Dec;90(6):550-555. Epub 2016 Jun 2 doi: 10.1111/cge.12781. PMID: 27040866

Diagnosis

Lin PY, Tseng MH, Zenker M, Rao J, Hildebrandt F, Lin SH, Lin CC, Chang JH, Hsu CH, Lee MD, Lin SP, Tsai JD
Orphanet J Rare Dis 2018 Dec 17;13(1):226. doi: 10.1186/s13023-018-0961-9. PMID: 30558655Free PMC Article
Abdel-Hamid MS, Ismail MF, Darwish HA, Effat LK, Zaki MS, Abdel-Salam GM
Am J Med Genet A 2016 Aug;170(8):2133-40. Epub 2016 Jun 2 doi: 10.1002/ajmg.a.37724. PMID: 27250695
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
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
Roberts E, Jackson AP, Carradice AC, Deeble VJ, Mannan J, Rashid Y, Jafri H, McHale DP, Markham AF, Lench NJ, Woods CG
Eur J Hum Genet 1999 Oct-Nov;7(7):815-20. doi: 10.1038/sj.ejhg.5200385. PMID: 10573015

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
Zombor M, Kalmár T, Nagy N, Berényi M, Telcs B, Maróti Z, Brandau O, Sztriha L
J Appl Genet 2019 May;60(2):151-162. Epub 2019 Feb 1 doi: 10.1007/s13353-019-00486-y. PMID: 30706430

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
Zorn M, Kühnisch J, Bachmann S, Seifert W
Sci Rep 2022 Jun 11;12(1):9686. doi: 10.1038/s41598-022-13717-w. PMID: 35690661Free 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
Hashmi JA, Al-Harbi KM, Ramzan K, Albalawi AM, Mehmood A, Samman MI, Basit S
Ann Saudi Med 2016 Nov-Dec;36(6):391-396. doi: 10.5144/0256-4947.2016.391. PMID: 27920410Free PMC Article
Kumar A, Girimaji SC, Duvvari MR, Blanton SH
Am J Hum Genet 2009 Feb;84(2):286-90. doi: 10.1016/j.ajhg.2009.01.017. PMID: 19215732Free 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
Zorn M, Kühnisch J, Bachmann S, Seifert W
Sci Rep 2022 Jun 11;12(1):9686. doi: 10.1038/s41598-022-13717-w. PMID: 35690661Free PMC Article
Carvalhal S, Bader I, Rooimans MA, Oostra AB, Balk JA, Feichtinger RG, Beichler C, Speicher MR, van Hagen JM, Waisfisz Q, van Haelst M, Bruijn M, Tavares A, Mayr JA, Wolthuis RMF, Oliveira RA, de Lange J
Sci Adv 2022 Jan 21;8(3):eabk0114. Epub 2022 Jan 19 doi: 10.1126/sciadv.abk0114. PMID: 35044816Free 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
Hashmi JA, Al-Harbi KM, Ramzan K, Albalawi AM, Mehmood A, Samman MI, Basit S
Ann Saudi Med 2016 Nov-Dec;36(6):391-396. doi: 10.5144/0256-4947.2016.391. PMID: 27920410Free PMC Article

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