Autosomal recessive primary microcephaly

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."

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.

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.

The prevalence of all forms of microcephaly that are present from birth (primary microcephaly) ranges from 1 in 30,000 to 1 in 250,000 newborns worldwide. About 200 families with MCPH have been reported in the medical literature. This condition is more common in several specific populations, such as in northern Pakistan, where it affects an estimated 1 in 10,000 newborns.

MCPH can result from mutations in at least seven genes. Mutations in the ASPM gene are the most common cause of the disorder, accounting for about half of all cases.

The genes associated with MCPH play important roles in early brain development, particularly in determining brain size. Studies suggest that the proteins produced from many of these genes help regulate cell division in the developing brain.

Mutations in any of the genes associated with MCPH impair early brain development. As a result, affected infants have fewer nerve cells (neurons) than normal and are born with an unusually small brain. The reduced brain size underlies the small head size, intellectual disability, and developmental delays seen in many affected individuals.

Genetic Testing Information

• Genetic Testing Registry: Microcephaly 1, primary, autosomal recessive
• Genetic Testing Registry: Microcephaly 2, primary, autosomal recessive, with or without cortical malformations
• Genetic Testing Registry: Microcephaly 3, 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 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 2, PRIMARY, AUTOSOMAL RECESSIVE, WITH OR WITHOUT CORTICAL MALFORMATIONS; MCPH2
• MICROCEPHALY 4, PRIMARY, AUTOSOMAL RECESSIVE; MCPH4
• MICROCEPHALY 3, PRIMARY, AUTOSOMAL RECESSIVE; MCPH3
• MICROCEPHALY 6, PRIMARY, AUTOSOMAL RECESSIVE; MCPH6
• MICROCEPHALY 5, PRIMARY, AUTOSOMAL RECESSIVE; MCPH5
• MICROCEPHALY 7, PRIMARY, AUTOSOMAL RECESSIVE; MCPH7

Scientific Articles on PubMed

• 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
• 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
• 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, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from http://www.ncbi.nlm.nih.gov/books/NBK555474/ 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