Microcephalic osteodysplastic primordial dwarfism

Microcephalic osteodysplastic primordial dwarfism, type 2 (MOPD2) is a type of primordial dwarfism that occurs as the result of undergrowth in the womb. MOPD2 is characterized by short stature, small head size (microcephaly) and associated skeletal abnormalities. The average height of these affected individual ranges from 20 inches to 40 inches.  It affects around 1 in 3 million people and equally develops in males and females of all ethnic groups.

Causes

MOPD2 develops as the result of a mutation in the gene identified as PCNT which produces a protein called pericentrin. This protein is located in structures known as centrosomes that play an essential role in cell division. The pericentrin functions as the anchoring protein that is responsible for securing other proteins to the centrosome. Pericentrin acts in the regulation of the cell cycle which is the process of cell’s replication. The genetic mutation results in the production of nonfunctional pericentrin which cannot anchor other essential proteins to the centrosome thus affecting the normal process of cell cycle and cell division. The reduction in the number of cells results in the features associated with this condition such as short bones and small sized head. This disorder is inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective. The parents of the affected individual each carry one copy of the defective gene but don’t necessarily exhibit the symptoms of this condition.

Symptoms

The features of MOPD2 include small sized head (microcephaly), low birth weight at full term delivery that is normally under 1kg, sparse hair, dental anomalies such as very small missing teeth, shortening of the forearm, skin that can develop blotchy pigment, precocious in some girls, kidney structural abnormalities and adult height that is typically less than 1m. Additional symptoms can include scoliosis and kyphosis which is the outward curvature of the spine, dislocation of the hip, bowing of the knees, farsightedness and aneurysms which can cause stroke-like episodes.

Diagnosis

The prenatal diagnosis is possible with the amniocentesis or chorionic villus sampling if this disorder is identified in the family. After the birth of the infant, the diagnosis of this condition is possible by evaluation of the medical and family history, identification of physical features and x-rays. Aneurysms which are the small pouching out of the blood vessels of the brain can be diagnosed with the procedure known as angiography that involves the dye injected into the arteries of the brain to detect the location of the problem. The genetic mutation responsible for developing this condition can be identified to confirm the diagnosis.

Treatment

There is no cure for this disease but the treatment can assist in reducing the symptoms evident in each case. Feeding problems in most of the cases are apparent which can be treated either with the nasogastric feeding or by helping the affected individual feed small quantity of food. The use of growth hormones does not help these cases. Monitoring is also essential to identify the development of farsightedness, kidney anomalies and the possibility of stroke. Psychological support may be beneficial for some of the affected cases and their families.

References

https://www.cafamily.org.uk/medical-information/conditions/m/majewski-osteodysplastic-primordial-dwarfism-type-ii/

https://rarediseases.info.nih.gov/diseases/9844/microcephalic-osteodysplastic-primordial-dwarfism-type-2

https://ghr.nlm.nih.gov/condition/microcephalic-osteodysplastic-primordial-dwarfism-type-ii#inheritance