Autosomal recessive primary microcephaly is characterized by an unusually small head size (microcephaly) that is noticeable at birth or soon after. Affected infants typically have intellectual disabilities, which can range from mild to severe. 

Autosomal recessive primary microcephaly is defined by an unusually small head circumference. 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. Infants with autosomal recessive primary microcephaly also have a brain that is smaller than usual. Although the head and brain grow throughout childhood and adolescence, they continue to be smaller than normal in affected individuals.

The smaller brain size contributes to the intellectual disabilities seen in people with autosomal recessive primary microcephaly. Delayed speech and language development are common. Some affected individuals have other brain abnormalities, which can include malformations of the outer surface of the brain (cerebral cortex). These cortical malformations may also contribute to the intellectual disabilities seen in affected individuals.

A few additional features have been associated with autosomal recessive primary microcephaly. These include seizures, behavioral issues, and problems with balance and coordination (ataxia). The development of motor skills, such as sitting, standing, and walking, may also be delayed.

Autosomal recessive primary microcephaly occurs in approximately 1 in 30,000 to 1 in 250,000 newborns. The condition is more common in parts of Asia and the Middle East, where as many as 1 in 10,000 newborns may be affected. More than 300 families with autosomal recessive primary microcephaly have been reported in the scientific literature. 

Genetic changes that cause disease are called pathogenic variants. Pathogenic variants in more than 20 different genes can cause autosomal recessive primary microcephaly. The signs and symptoms that are seen in affected individuals may vary depending on the particular gene involved. Pathogenic variants in the ASPM gene are the most common cause of autosomal recessive primary microcephaly, accounting for 25 to 50 percent of all cases. Pathogenic variants in the WDR62 gene are the second most common cause. The remaining genes are each responsible for a small percentage of cases.

The ASPM and WDR62 genes provide instructions for making proteins that are involved in cell division. These proteins appear to be particularly important for the division of cells in the developing brain. The pathogenic variants in the ASPM and WDR62 genes that cause autosomal recessive primary microcephaly lead to the production of abnormal proteins. These proteins affect the cells of the developing brain, impairing their ability to divide. As a result, affected infants have fewer nerve cells (neurons) than normal and are born with unusually small brains. The smaller brain size contributes to the smaller head size and the intellectual disabilities seen in affected individuals.

Many of the other genes that are associated with autosomal recessive primary microcephaly are also thought to play important roles in early brain development, particularly in determining brain size. Studies suggest that the proteins that are produced from many of these genes help regulate cell division in the developing brain.

Some people with autosomal recessive primary microcephaly do not have one of the pathogenic variants that are known to cause this condition. In these individuals, the cause of the condition is unknown.

Genetic Testing Information

• Genetic Testing Registry: Autosomal recessive primary microcephaly
• Genetic Testing Registry: Microcephaly 1, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 11, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 12, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 13, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 14, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 2, primary, autosomal recessive, with or without cortical malformations
• Genetic Testing Registry: Microcephaly 28, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 29, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 3, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 30, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 4, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 5, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 6, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 7, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 8, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 9, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 16, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 17, primary, autosomal recessive
• Genetic Testing Registry: MICROCEPHALY 19, PRIMARY, AUTOSOMAL RECESSIVE
• Genetic Testing Registry: MICROCEPHALY 20, PRIMARY, AUTOSOMAL RECESSIVE
• Genetic Testing Registry: MICROCEPHALY 21, PRIMARY, AUTOSOMAL RECESSIVE
• Genetic Testing Registry: MICROCEPHALY 22, PRIMARY, AUTOSOMAL RECESSIVE
• Genetic Testing Registry: MICROCEPHALY 23, PRIMARY, AUTOSOMAL RECESSIVE
• Genetic Testing Registry: MICROCEPHALY 24, PRIMARY, AUTOSOMAL RECESSIVE
• Genetic Testing Registry: MICROCEPHALY 25, PRIMARY, AUTOSOMAL RECESSIVE

Genetic and Rare Diseases Information Center

• Autosomal recessive primary microcephaly

Patient Support and Advocacy Resources

• National Organization for Rare Disorders (NORD)

Catalog of Genes and Diseases from OMIM

• MICROCEPHALY 1, PRIMARY, AUTOSOMAL RECESSIVE; MCPH1
• MICROCEPHALY 10, PRIMARY, AUTOSOMAL RECESSIVE; MCPH10
• MICROCEPHALY 11, PRIMARY, AUTOSOMAL RECESSIVE; MCPH11
• MICROCEPHALY 12, PRIMARY, AUTOSOMAL RECESSIVE; MCPH12
• MICROCEPHALY 13, PRIMARY, AUTOSOMAL RECESSIVE; MCPH13
• MICROCEPHALY 14, PRIMARY, AUTOSOMAL RECESSIVE; MCPH14
• MICROCEPHALY 16, PRIMARY, AUTOSOMAL RECESSIVE; MCPH16
• MICROCEPHALY 17, PRIMARY, AUTOSOMAL RECESSIVE; MCPH17
• MICROCEPHALY 19, PRIMARY, AUTOSOMAL RECESSIVE; MCPH19
• MICROCEPHALY 2, PRIMARY, AUTOSOMAL RECESSIVE, WITH OR WITHOUT CORTICAL MALFORMATIONS; MCPH2
• MICROCEPHALY 20, PRIMARY, AUTOSOMAL RECESSIVE; MCPH20
• MICROCEPHALY 21, PRIMARY, AUTOSOMAL RECESSIVE; MCPH21
• MICROCEPHALY 22, PRIMARY, AUTOSOMAL RECESSIVE; MCPH22
• MICROCEPHALY 23, PRIMARY, AUTOSOMAL RECESSIVE; MCPH23
• MICROCEPHALY 24, PRIMARY, AUTOSOMAL RECESSIVE; MCPH24
• MICROCEPHALY 25, PRIMARY, AUTOSOMAL RECESSIVE; MCPH25
• MICROCEPHALY 28, PRIMARY, AUTOSOMAL RECESSIVE; MCPH28
• MICROCEPHALY 29, PRIMARY, AUTOSOMAL RECESSIVE; MCPH29
• MICROCEPHALY 3, PRIMARY, AUTOSOMAL RECESSIVE; MCPH3
• MICROCEPHALY 30, PRIMARY, AUTOSOMAL RECESSIVE; MCPH30
• MICROCEPHALY 4, PRIMARY, AUTOSOMAL RECESSIVE; MCPH4
• MICROCEPHALY 5, PRIMARY, AUTOSOMAL RECESSIVE; MCPH5
• MICROCEPHALY 6, PRIMARY, AUTOSOMAL RECESSIVE; MCPH6
• MICROCEPHALY 7, PRIMARY, AUTOSOMAL RECESSIVE; MCPH7
• MICROCEPHALY 8, PRIMARY, AUTOSOMAL RECESSIVE; MCPH8
• MICROCEPHALY 9, PRIMARY, AUTOSOMAL RECESSIVE; MCPH9

Scientific Articles on PubMed

• PubMed

• Barbelanne M, Tsang WY. Molecular and cellular basis of autosomal recessive primary microcephaly. Biomed Res Int. 2014;2014:547986. doi: 10.1155/2014/547986. Epub 2014 Dec 8. Citation on PubMed
• Bolat H, Sager SG, Turkyilmaz A, Cebi AH, Akin Y, Onay H, Ozkinay F, Unsel-Bolat G. Autosomal Recessive Primary Microcephaly (MCPH) and Novel Pathogenic Variants in ASPM and WDR62 Genes. Mol Syndromol. 2022 Dec;13(5):363-369. doi: 10.1159/000524391. Epub 2022 Apr 27. Citation on PubMed
• Cox J, Jackson AP, Bond J, Woods CG. What primary microcephaly can tell us about brain growth. Trends Mol Med. 2006 Aug;12(8):358-66. doi: 10.1016/j.molmed.2006.06.006. Epub 2006 Jul 10. Citation on PubMed
• Kaindl AM, Passemard S, Kumar P, Kraemer N, Issa L, Zwirner A, Gerard B, Verloes A, Mani S, Gressens P. Many roads lead to primary autosomal recessive microcephaly. Prog Neurobiol. 2010 Mar;90(3):363-83. doi: 10.1016/j.pneurobio.2009.11.002. Epub 2009 Dec 2. Citation on PubMed
• Naveed M, Kazmi SK, Amin M, Asif Z, Islam U, Shahid K, Tehreem S. Comprehensive review on the molecular genetics of autosomal recessive primary microcephaly (MCPH). Genet Res (Camb). 2018 Aug 8;100:e7. doi: 10.1017/S0016672318000046. Citation on PubMed
• 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, Megarbane A, Moog U, Odent S, Hernandez K, Pouvreau N, Scala I, Schaer M, Gressens P, Gerard B, Verloes A. Expanding the clinical and neuroradiologic phenotype of primary microcephaly due to ASPM mutations. Neurology. 2009 Sep 22;73(12):962-9. doi: 10.1212/WNL.0b013e3181b8799a. Citation on PubMed
• Roberts E, Hampshire DJ, Pattison L, Springell K, Jafri H, Corry P, Mannon J, Rashid Y, Crow Y, Bond J, Woods CG. Autosomal recessive primary microcephaly: an analysis of locus heterogeneity and phenotypic variation. J Med Genet. 2002 Oct;39(10):718-21. doi: 10.1136/jmg.39.10.718. Citation on PubMed or Free article on PubMed Central
• Ruaud L, Drunat S, Elmaleh-Berges M, Ernault A, Guilmin Crepon S; MCPH Consortium; El Ghouzzi V, Auvin S, Verloes A, Passemard S. Neurological outcome in WDR62 primary microcephaly. Dev Med Child Neurol. 2022 Apr;64(4):509-517. doi: 10.1111/dmcn.15060. Epub 2021 Sep 25. Citation on PubMed
• Thornton GK, Woods CG. Primary microcephaly: do all roads lead to Rome? Trends Genet. 2009 Nov;25(11):501-10. doi: 10.1016/j.tig.2009.09.011. Epub 2009 Oct 21. Citation on PubMed or Free article on PubMed Central
• Verloes A, Drunat S, Passemard S. ASPM Primary Microcephaly. 2020 Apr 2. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK555474/ Citation on PubMed
• Verloes A, Ruaud L, Drunat S, Passemard S. WDR62 Primary Microcephaly. 2022 Feb 17. In: Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK578067/ Citation on PubMed
• Woods CG, Bond J, Enard W. Autosomal recessive primary microcephaly (MCPH): a review of clinical, molecular, and evolutionary findings. Am J Hum Genet. 2005 May;76(5):717-28. doi: 10.1086/429930. Epub 2005 Mar 31. Citation on PubMed or Free article on PubMed Central
• Zaqout S, Kaindl AM. Autosomal Recessive Primary Microcephaly: Not Just a Small Brain. Front Cell Dev Biol. 2022 Jan 17;9:784700. doi: 10.3389/fcell.2021.784700. eCollection 2021. Citation on PubMed
• Zaqout S, Morris-Rosendahl D, Kaindl AM. Autosomal Recessive Primary Microcephaly (MCPH): An Update. Neuropediatrics. 2017 Jun;48(3):135-142. doi: 10.1055/s-0037-1601448. Epub 2017 Apr 11. Citation on PubMed