Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II) is an inherited genetic condition and one of the most common forms of microcephalic primordial dwarfism. The disorder is defined by significant growth failure that begins before birth. Its name describes its three prominent features: an atypically small head (microcephaly), abnormal bone development (osteodysplasia), and primordial dwarfism.
This condition is rare, affecting approximately 1 in 3 million people. Individuals with MOPD II are born very small for their gestational age and grow at a very slow pace. The condition involves a recognizable set of physical traits and an increased likelihood of specific health issues that require ongoing medical attention.
Genetic Origins of MOPD II
The cause of MOPD II is mutations within the pericentrin (PCNT) gene. The PCNT gene holds the instructions for producing a protein called pericentrin. This protein is a component of cellular structures known as centrosomes, which act as organizing centers for cell division. Pericentrin’s job is to anchor other proteins to the centrosome, ensuring that cells can divide correctly and maintain their structure.
Mutations in both copies of the PCNT gene lead to a shortened, nonfunctional pericentrin protein. Without functional pericentrin, centrosomes cannot properly assemble the components needed for cell division. This disruption impairs the body’s ability to produce new cells efficiently, leading to the profound growth failure and skeletal abnormalities seen in MOPD II.
MOPD II is inherited in an autosomal recessive pattern. This means a child must inherit one copy of the mutated PCNT gene from each parent to have the condition. The parents, who each carry only one mutated copy, are considered carriers and do not show any signs of the disorder. When both parents are carriers, there is a 25% chance with each pregnancy that the child will be affected by MOPD II.
Defining Physical and Developmental Features
The most defining characteristic of MOPD II is severe growth restriction that begins in the womb, a condition known as intrauterine growth restriction (IUGR). Newborns with MOPD II are very small, with a weight and length comparable to a premature infant. This slow growth continues after birth, leading to an adult height that ranges between 20 and 40 inches.
The head is also significantly small at birth and grows much slower than the rest of the body, resulting in disproportionate microcephaly. Although the adult head circumference is small, similar to that of a typical infant, intelligence is often in the normal to near-normal range. Some individuals may have mild learning disabilities, and the voice is characteristically high-pitched and nasal.
Distinctive craniofacial features become more apparent during the first year of life. These include a prominent nose, a small jaw (micrognathia), and eyes that appear large in a small face. The teeth are also affected; they are often small, have deficient enamel, and may have abnormal roots, which can lead to early tooth loss.
Skeletal abnormalities are a component of the disorder. The bones in the arms and legs may be thin and delicate. Many individuals experience abnormal development of the hip joints (hip dysplasia), and some develop a side-to-side curvature of the spine (scoliosis). The forearms are disproportionately short, a feature referred to as mesomelia.
Significant Health Complications
Individuals with MOPD II face significant health challenges beyond their physical traits, particularly vascular abnormalities affecting the brain. A large percentage of people with this condition develop cerebrovascular issues, such as brain aneurysms, which are weak, bulging spots on an artery wall that can rupture. Regular screening with magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) is recommended to monitor for these changes.
Another common vascular problem is Moyamoya disease, where arteries at the base of the brain become narrowed, restricting blood flow. The body attempts to compensate by forming a network of tiny, fragile collateral vessels. These vascular conditions increase the risk of stroke, even at a young age, and are a focus of medical monitoring. If detected early, treatments like revascularization surgery can be effective.
Endocrine problems are also very common, with many individuals developing insulin resistance over time. This condition, where the body’s cells do not respond effectively to insulin, often leads to type 2 diabetes, sometimes beginning in childhood. Regular screening for insulin resistance, including lipid profiles, is an important part of care, starting around school age.
Some individuals with MOPD II may experience hematological issues related to the blood. This can include abnormal blood cell counts, such as anemia (low red blood cells) or thrombocytosis (high platelet counts). Additionally, structural abnormalities of the kidneys can be present, which may contribute to hypertension later in life.
Diagnosis and Multidisciplinary Management
The diagnosis of MOPD II is often first suspected based on its characteristic features. Prenatal ultrasounds may reveal severe intrauterine growth restriction. At birth, the combination of profound short stature, significant microcephaly, and specific facial and skeletal features points toward a primordial dwarfism syndrome. Skeletal X-rays can show delayed bone age and specific changes in the hips and other bones, helping support the diagnosis.
Definitive confirmation is achieved through molecular genetic testing to identify mutations in the PCNT gene. Identifying the specific genetic cause is important because it distinguishes MOPD II from other types of primordial dwarfism and helps guide medical management, particularly screening for associated vascular complications.
There is no cure for MOPD II, so management focuses on treating symptoms and proactively monitoring for known complications. This requires a coordinated, multidisciplinary team of specialists, which includes:
- A pediatrician to provide general oversight.
- An orthopedist to manage skeletal issues like scoliosis and hip dysplasia.
- A neurologist or neurosurgeon to screen for and treat brain aneurysms and Moyamoya disease.
- An endocrinologist to monitor for insulin resistance and diabetes.
- A dentist with experience in genetic conditions to address complex dental abnormalities.
- A geneticist to provide information and counseling to the family.