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Autosomal Recessive Primary Microcephaly (MCPH)

What is Autosomal Recessive Primary Microcephaly (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 volume. Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. The 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 also have a brain volume that is smaller than usual. They typically do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but continue on to be much smaller than the head and brain of children in their age group.

MCPH is associated with varying degrees of intellectual disability. Individuals with MCPH do not usually have abnormalities of the internal organs (visceral malformations).

Certain genes that cause MCPH can also cause a rare disorder known as Seckel syndrome. Some researchers believe that these disorders may represent a spectrum of disease rather than distinct disorders.

 

 

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 volume. Infants with MCPH have an unusually small head circumference compared to other infants of the same sex and age. The 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 also have a brain volume that is smaller than usual. They typically do not have any major abnormalities in the structure of the brain. The head and brain grow throughout childhood and adolescence, but continue on to be much smaller than the head and brain of children in their age group.

MCPH is associated with varying degrees of intellectual disability. Individuals with MCPH do not usually have abnormalities of the internal organs (visceral malformations).

Certain genes that cause MCPH can also cause a rare disorder known as Seckel syndrome. Some researchers believe that these disorders may represent a spectrum of disease rather than distinct disorders.

 

Acknowledgement of Autosomal Recessive Primary Microcephaly (MCPH) has not been added yet.

The prevalence of all forms of microcephaly from birth ranges from 1 in 30,000 to 1 in 250,000 newborns worldwide. The exact prevalence of MCPH is unknown. In Caucasian populations, it is estimated to occur in 1 per 1,000,000 people in the general population. The condition is more common in several specific regions, such as northern Pakistan, where it affects an estimated 1 in 10,000 newborns.

Synonyms for Autosomal Recessive Primary Microcephaly (MCPH) has not been added yet.

MCPH can result from mutations in at least twelve genes. Mutations in the ASPM gene are the most common cause. The genes associated play an important role in early brain development, especially in determining the size of the brain. Studies suggest that proteins produced from many of these genes help regulate cell division in the developing brain. As a result of the mutations, 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, developmental delays, and intellectual disability seen in many affected individuals.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell need to have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but do not show signs and symptoms of the condition. Each parent must pass on the altered copy of the gene to their child for the disorder to appear. If only one parent passes on the altered gene, the child would be a carrier for MCPH but not suffer from the disease.

Affected individuals have a reduction in head circumference at birth at least 2 standard deviations below the average size. MCPH can be observed by week 32 of pregnancy. As the affected individual ages, the head grows very slowly. The head circumference may be 3 standard deviations below the average before 6 months of age, and  4 to 12 standard deviations below the average as adults. Mild to moderate, non-progressive intellectual impairment is present if there is no significant neurological disorder.

Seizures may be present in certain individuals, specifically those with a mutation in the ASPM gene. Many affected individuals have hyperactive behavior, problems with keeping attention, delays in early motor milestones (e.g. sitting, standing, walking) and delays in the development of speech.

Most children with MCPH are of normal height and weight. However, some children with specific genetic mutations may be much shorter than average (short stature).

Name Description
Autosomal Recessive Primary Microcephaly MCPH
Microcephalia vera MCPH
Microcephaly vera MCPH
True microcephaly MCPH

Diagnosis is based on clinical signs. The most common diagnostic criteria is reduced occipitofrontal (head) circumference, mild to moderate intellectual disability, lack of other malformations or differences in body structure, and a normal to mild shortened height. The condition can be diagnosed on prenatal ultrasound (imaging technique that uses high-frequency sound waves to produce images of a fetus in the uterus). However, the absence of microcephaly in the ultrasound does not mean that the infant does not have microcephaly.

Prenatal (before birth) testing is available for families with known gene mutations. Magnetic resonance imaging (MRI) may demonstrate a proportionately small-sized brain without other structural abnormalities, but normal findings do not exclude the diagnosis.

A diagnosis can be confirmed through molecular genetic testing, which can identify a mutation in one of the genes that cause autosomal recessive primary microcephaly.

There is no treatment for autosomal recessive primary microcephaly, but rather treatment for each specific symptom. Therapy is supportive, and involves special education programs tailored to the affected individual’s needs. This can include speech and language therapy, occupational therapy, and behavioral therapy as needed. There are also community services that provide support for families. Seizures are usually responsive to monotherapy (treatment of a disease with a single drug) with standard antiepileptic drugs (AEDs). Individuals with mild growth retardation may consider growth hormones.

Genetic counseling is recommended for families with a child with autosomal recessive primary microcephaly.

Prognosis depends on severity and related manifestations. Generally, with appropriate support, many affected individuals live somewhat near normal lives. Anecdotal reports document survival (without obvious complications) in person older than age 50 years.

Tips or Suggestions of Autosomal Recessive Primary Microcephaly (MCPH) has not been added yet.

Autosomal Recessive Primary Microcephaly. Genetic Home Reference website. http://ghr.nlm.nih.gov/condition/autosomal-recessive-primary-microcephaly

Barbelanne M, Tsang WY. Molecular and cellular basis of autosomal recessive primary microcephaly. Biomed Res Int. 2014;2014:547986.

Faheem M, Naseer MI, Rasool M, et al. Molecular genetics of human primary microcephaly: an overview. BMC Med Genomics. 2015;8 Suppl 1:S4.

Ghafouri-Fard S, Fardaei M, Gholami M, Miryounesi M. A case report: autosomal recessive microcephaly caused by a novel mutation in MCPH1 gene. Gene. 2015;57(1):149-150.

Mahmood S, Ahmad W, Hassan MJ. Autosomal recessive primary microcephaly (MCPH): clinical manifestations, genetic heterogeneity and mutation continuum. Orphanet J Rare Dis. 2011;6:39.

Verloes A, Drunat S, Gressens P, Passemard S. Primary Autosomal Recessive Microcephalies and Seckel Syndrome Spectrum Disorders. GeneReviews website. http://www.ncbi.nlm.nih.gov/books/NBK9587/ 

Verloes A. Autosomal Recessive Primary Microcephaly. Orphanet website. http://www.orpha.net/consor4.01/www/cgi-bin/OC_Exp.php?lng=EN&Expert=2512  

I was wondering... Created by miltarywife
Last updated 7 Dec 2010, 10:25 AM

Posted by gillianharron1983
7 Dec 2010, 10:25 AM

My baby was diagnosed at birth with microcephaly too. Obvious from his very small head circumference. MRI indicated pachygyria. Similarly doctors say everything unknown so I sympathise and understand. Baby is now 8 months (corrected age). He has been and still is difficult to feed (GERD). He has an overall stiffness, physio since 6 weeks has been a huge help. Development delay only really obvious from 5/6 months. He is not able to sit up by himself, doesn't seem to want to roll over or crawl and has only ever made a few 'aboo' 'aroo' noises. At the same time however he has surpassed all professionals expectations. For example they thought he would never co-ordinate his right side with his left and now he is happily passing objects between his two hands. It is very difficult to accept that you won't know what the future holds for your baby. My best advise is to take each day as it comes. Enjoy your little girl for who she is.

Posted by miltarywife
1 Dec 2010, 11:01 PM

I have a 11 week old little girl, who at birth was diagnosed with microcephaly. She has had MRI's, ultrasounds and ct's done which showed excess fluid in/around her brain. She was also diagnosed with Diffuse Brain Atrophy (which they say will lead to developmental delays), Persistent Fetal Vascular Syndrome (blindness), Atrial Septal Defect, Peripheral pulmonic stenosis (both involve her heart ASD is a hole and PPS is a murmur), Chromosome 4q deletion syndrome (don't have a clue what that will affect yet) and failure to thrive. I was just wondering if anyone else's child/ren have any of these other issues or if they had any issues at all as they have grown up. The doctors are all saying everything is unknown. Any help would be greatly appreciated.

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I was wondering...

Created by miltarywife | Last updated 7 Dec 2010, 10:25 AM


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