Autosomal recessive primary microcephaly

Description

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.

Frequency

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.

Causes

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.

Inheritance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell must have a pathogenic variant to cause the disorder. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

Autosomal recessive inheritance. Credit: U.S. National Library of Medicine.

Other Names for This Condition

• MCPH
• Microcephaly primary autosomal recessive
• Primary autosomal recessive microcephaly

Where this page came from

This page was imported from MedlinePlus Genetics, National Library of Medicine. Courtesy of MedlinePlus from the National Library of Medicine; its genetics summaries and the illustrations credited to the library are in the public domain. Pictures credited to others are not copied.

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