Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is a condition characterized by short stature (dwarfism) with other skeletal abnormalities (osteodysplasia) and an unusually small head size (microcephaly). The growth problems in MOPDII are primordial, meaning they begin before birth, with affected individuals showing slow prenatal growth (intrauterine growth retardation). After birth, affected individuals continue to grow at a very slow rate. The final adult height of people with this condition ranges from 20 inches to 40 inches. Other skeletal abnormalities in MOPDII include abnormal development of the hip joints (hip dysplasia), thinning of the bones in the arms and legs, an abnormal side-to-side curvature of the spine (scoliosis), and shortened wrist bones. In people with MOPDII head growth slows over time; affected individuals have an adult brain size comparable to that of a 3-month-old infant. However, intellectual development is typically normal.

People with this condition have a high-pitched, nasal voice and some have a narrowing of the voicebox (subglottic stenosis). Facial features characteristic of MOPDII include a prominent nose, full cheeks, a long midface, and a small jaw. Other signs and symptoms seen in some people with MOPDII include small teeth (microdontia) and farsightedness. Over time, affected individuals may develop areas of abnormally light or dark skin coloring (pigmentation).

Many individuals with MOPDII have blood vessel abnormalities. For example, some affected individuals develop a bulge in one of the blood vessels at the center of the brain (intracranial aneurysm). These aneurysms are dangerous because they can burst, causing bleeding within the brain. Some affected individuals have Moyamoya disease, in which arteries at the base of the brain are narrowed, leading to restricted blood flow. These vascular abnormalities are often treatable, though they increase the risk of stroke and reduce the life expectancy of affected individuals.

Mutations in the PCNT gene cause MOPDII. The PCNT gene provides instructions for making a protein called pericentrin. Within cells, this protein is located in structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules. Microtubules are fibers that help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells. Pericentrin acts as an anchoring protein, securing other proteins to the centrosome. Through its interactions with these proteins, pericentrin plays a role in regulation of the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion.

PCNT gene mutations lead to the production of a nonfunctional pericentrin protein that cannot anchor other proteins to the centrosome. As a result, centrosomes cannot properly assemble microtubules, leading to disruption of the cell cycle and cell division. Impaired cell division causes a reduction in cell production, while disruption of the cell cycle can lead to cell death. This overall reduction in the number of cells leads to short bones, microcephaly, and the other signs and symptoms of MOPDII.

Normal Function

The PCNT gene provides instructions for making a protein called pericentrin. Within cells, this protein is located in structures called centrosomes. Centrosomes play a role in cell division and the assembly of microtubules. Microtubules are fibers that help cells maintain their shape, assist in the process of cell division, and are essential for the transport of materials within cells.

Pericentrin acts as an anchoring protein, securing proteins to the centrosome that are necessary for its function. Through its interactions with these proteins, pericentrin is involved in the regulation of the cell cycle, which is the cell's way of replicating itself in an organized, step-by-step fashion.

Health Conditions Related to Genetic Changes

Microcephalic osteodysplastic primordial dwarfism type II

At least 30 mutations in the PCNT gene have been found to cause microcephalic osteodysplastic primordial dwarfism type II (MOPDII). These mutations result in the production of an abnormally short, nonfunctional pericentrin protein that cannot anchor other proteins to the centrosome. As a result, centrosomes cannot properly assemble microtubules, leading to disruption of the cell cycle and cell division. Impaired cell division causes a reduction in cell production, while disruption of the cell cycle can lead to cell death. This overall reduction in the number of cells leads to short bones, microcephaly, and the other signs and symptoms of MOPDII.

Prostate cancer

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Cancers

Gene mutations can be acquired during a person's lifetime and are present only in certain cells. These mutations are called somatic mutations, and they are not inherited. Somatic mutations in the PCNT gene can cause an increase in production of the pericentrin protein. Increased levels of pericentrin have been found in solid tumors (including prostate tumors) as well as cancers of blood-forming cells (leukemia and lymphoma). More pericentrin within the centrosome leads to overactivation of the cell cycle and increased cell division. This abnormal cell growth and division can eventually lead to a cancerous tumor.

Other disorders

Certain common genetic variations (polymorphisms) in the PCNT gene have been associated with an increased risk of developing psychiatric disorders such as schizophrenia and depression in some individuals. Similarly, increased levels of pericentrin have been found in some individuals with bipolar disorder. It is unclear how changes in the PCNT gene or increased levels of pericentrin protein are related to these disorders. A large number of genetic and environmental factors, most of which remain unknown, likely determine the risk of developing these complex conditions.

Other Names for This Gene

• PCN
• PCNT2
• PCNT_HUMAN
• PCNTB
• pericentrin B
• pericentrin-2

Genomic Location

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.

MOPDII appears to be a rare condition, although its prevalence is unknown.