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Genetics Home Reference: your guide to understanding genetic conditions
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Autosomal recessive primary microcephaly

(often shortened to MCPH)
Reviewed April 2011

What is MCPH?

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 worsen 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.

How common is MCPH?

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.

What genes are related to MCPH?

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.

Related Gene(s)

Changes in these genes are associated with autosomal recessive primary microcephaly.

  • ASPM
  • CDK5RAP2
  • CENPJ
  • CEP152
  • MCPH1
  • STIL
  • WDR62

How do people inherit MCPH?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of MCPH?

These resources address the diagnosis or management of MCPH and may include treatment providers.

  • Gene Review: Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders (http://www.ncbi.nlm.nih.gov/books/NBK9587)
  • Genetic Testing Registry: Primary autosomal recessive microcephaly 1 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1855081)
  • Genetic Testing Registry: Primary autosomal recessive microcephaly 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1858535)
  • Genetic Testing Registry: Primary autosomal recessive microcephaly 3 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1858108)
  • Genetic Testing Registry: Primary autosomal recessive microcephaly 4 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1858516)
  • Genetic Testing Registry: Primary autosomal recessive microcephaly 5 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1837501)
  • Genetic Testing Registry: Primary autosomal recessive microcephaly 6 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1842109)
  • Genetic Testing Registry: Primary autosomal recessive microcephaly 7 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C2675187)
  • MedlinePlus Encyclopedia: Head Circumference (http://www.nlm.nih.gov/medlineplus/ency/article/002379.htm)

You might also find information on the diagnosis or management of MCPH in Educational resources (http://www.ghr.nlm.nih.gov/condition/autosomal-recessive-primary-microcephaly/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/autosomal-recessive-primary-microcephaly/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about MCPH?

You may find the following resources about MCPH helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for MCPH?

  • microcephaly primary hereditary
  • primary autosomal recessive microcephaly
  • true microcephaly

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about MCPH?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding MCPH?

autosomal ; autosomal recessive ; cell ; cell division ; centrosome ; chromosome ; disability ; gene ; hereditary ; inherited ; microcephaly ; motor ; prevalence ; recessive ; short stature ; stature ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • 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. Epub 2006 Jul 10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16829198?dopt=Abstract)
  • Gene Review: Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders (http://www.ncbi.nlm.nih.gov/books/NBK9587)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19931588?dopt=Abstract)
  • 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. 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. (http://www.ncbi.nlm.nih.gov/pubmed/19770472?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/12362027?dopt=Abstract)
  • 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. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19850369?dopt=Abstract)
  • 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. Epub 2005 Mar 31. Review. (http://www.ncbi.nlm.nih.gov/pubmed/15806441?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: April 2011
Published: October 20, 2014