What are the other Names for this Condition? (Also known as/Synonyms)

• Microcephalia Vera
• Primary Hereditary Microcephaly
• True Microcephaly

What is Autosomal Recessive Primary Microcephaly? (Definition/Background Information)

• 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
• MCPH causes mild to moderate intellectual disability, which does not worsen with age, and also mild delayed speech, motor, and language skills 
• Some people with MCPH have a narrow, sloping forehead; mild seizures; problems with attention or behavior; or short stature, compared to others in their family. It normally does not affect any other major organ systems or cause other health problems
• Autosomal Recessive Primary Microcephaly can result from changes (mutations) in the ASPM gene (half of the cases) and at least other ten genes which are involved in early brain development and brain size. It is inherited in an autosomal recessive pattern
• There is no cure for Autosomal Recessive Primary Microcephaly and treatment is supportive

(Source: Autosomal Recessive Primary Microcephaly; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

Who gets Autosomal Recessive Primary Microcephaly? (Age and Sex Distribution)

• Autosomal Recessive Primary Microcephaly is a rare congenital disorder. The symptoms of the disorder may be apparent before or soon after birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Autosomal Recessive Primary Microcephaly? (Predisposing Factors)

• A positive family history may be an important risk factor, since Autosomal Recessive Primary Microcephaly can be inherited

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Autosomal Recessive Primary Microcephaly? (Etiology)

In about 50% of the cases, Autosomal Recessive Primary Microcephaly is caused by mutations in the ASPM gene.

• Changes in other genes that regulate early brain development and brain size may also cause the condition
• These genes may include MCPH1, WDR62, CDK5RAP2, CEP152, CENPJ, STIL, CEP63, CEP135, CASC5, and PHC1
• Autosomal Recessive Primary Microcephaly is inherited in an autosomal recessive manner

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Autosomal Recessive Primary Microcephaly?

The signs and symptoms of Autosomal Recessive Primary Microcephaly may vary among affected individuals in type and severity, and may include:

• Abnormal cortical bone morphology
• Agenesis of corpus callosum
• Global developmental delay
• Heterotopia
• Hyperreflexia
• Hypoplasia of the frontal lobes
• Sloping forehead
• Thin upper lip vermilion
• Upslanted palpebral fissure
• Unilateral renal agenesis
• Ventriculomegaly
• Vesicoureteral reflux

(Source: Autosomal Recessive Primary Microcephaly; Genetic and Rare Disease Information Center (GARD) of National Center for Advancing Translational Science (NCATS), USA.)

How is Autosomal Recessive Primary Microcephaly Diagnosed?

Autosomal Recessive Primary Microcephaly is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies, including prenatal ultrasound of the developing fetus after 32nd week of gestation
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Autosomal Recessive Primary Microcephaly?

The complications of Autosomal Recessive Primary Microcephaly may include:

• Seizures; risk of falls and injuries, if seizures are present
• Hyperactive behavior
• Possible renal insufficiency, due to unilateral renal agenesis

Complications may occur with or without treatment, and in some cases, due to treatment also

How is Autosomal Recessive Primary Microcephaly Treated?

There is no cure for Autosomal Recessive Primary Microcephaly, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Autosomal Recessive Primary Microcephaly be Prevented?

Autosomal Recessive Primary Microcephaly may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Autosomal Recessive Primary Microcephaly? (Outcomes/Resolutions)

• The prognosis of Autosomal Recessive Primary Microcephaly is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Autosomal Recessive Primary Microcephaly:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/