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Microcephalic primordial dwarfism (MPD)

Microcephalic primordial dwarfism (MPD)




overview

Microcephalic primordial dwarfism (MPD) is a group of rare genetic disorders causing severe growth restriction before and after birth, resulting in extremely small stature and head size (microcephaly), alongside skeletal issues (osteodysplasia) and other distinctive features, with MOPD II being the most common type, linked to PCNT gene mutations and known for vascular complications like aneurysms. Other types, like MOPD I, involve RNU4ATAC gene defects, causing severe CNS issues and often early death, while MOPD II patients often have normal intelligence but face serious health risks, including strokes. 

Type

MOPD Type I (MOPD I)

Genetics: Caused by mutations in the RNU4ATAC gene.

Key Features: Severe brain malformations (cerebral hypoplasia, agenesis of corpus callosum), severe microcephaly, limb deformities, skin issues, and very poor prognosis, often leading to early death. 

MOPD Type II (MOPD II)

Genetics: Caused by mutations in the PCNT gene.

Key Features:

Growth: Extreme short stature (adult height 20-40 inches), microcephaly.

Skeletal: Osteodysplasia (bone malformations), hip dysplasia, scoliosis, thin bones.

Vascular: High risk of moyamoya disease, intracranial aneurysms, stroke, and coronary artery disease.

Dental: Small teeth, poor oral health.

Metabolic: Insulin resistance, early-onset diabetes.

Other: High-pitched voice, distinct facial features (beaked nose, small jaw), but often normal intellect. 

Symptoms

Extreme Short Stature & Microcephaly: Very small size from birth, head growth slows, resulting in a brain size like an infant's, though often with normal intelligence.

Distinctive Face: Prominent nose, full cheeks, small jaw, long midface, often a high-pitched, nasal voice.

Skeletal Issues: Hip dysplasia, scoliosis (curved spine), thin bones in arms/legs, shortened wrists, early arthritis.

Dental: Small teeth (microdontia), early tooth loss, crowding

Causes

Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II): Most common, caused by mutations in the PCNT gene (pericentrin).

MOPD Type I: Linked to mutations in the RNU4ATAC gene, affecting small nuclear RNA.

Other Syndromes: Seckel Syndrome, Alazami Syndrome (due to ZNF335 deficiency), and others involve different gene mutations. 

Diagnosis

Clinical Observation:

Severe Growth Restriction: Very small at birth (intrauterine growth retardation), continuing postnatally.

Extreme Microcephaly: Head size significantly smaller than body and age-matched norms.

Facial Features: Prominent nose, small chin, large eyes, sometimes sloping forehead (MOPD1).

Skeletal Dysplasia: Hip deformities, scoliosis, thin bones, delayed bone age, short limbs (micromelia).

Other Signs: Dental issues (microdontia), vascular problems (moyamoya, aneurysms), kidney/metabolic issues (diabetes, hypertension).

Imaging (Radiology):

X-rays: Show skeletal abnormalities like hip issues, thin bones, or specific bone proportions.

Brain MRI: Can reveal brain anomalies like agenesis of the corpus callosum (MOPD1) or aneurysms.

Genetic Testing (Definitive):

Identifies mutations in genes like RNU4ATAC (MOPD1) or PCNT (MOPDII).

Uses methods like single-gene, multigene panels, or whole exome/genome sequencing.

Laboratory Tests:

Blood tests (CBC, liver/kidney function, hormones) to rule out overlapping syndromes (e.g., Fanconi anemia, Bloom syndrome). 

Treatments

Multidisciplinary Care: A team approach is vital, involving specialists in genetics, orthopedics, cardiology, neurology, dentistry, and education.

Symptomatic Treatment: Focuses on managing complications as they arise, rather than the underlying dwarfism.

Regular Surveillance: Frequent check-ups to monitor growth, development, and potential problems like cerebrovascular disease (aneurysms/strokes), diabetes, kidney issues, and skeletal deformities. 

Skeletal Issues: Orthopedic intervention for hip pathology (pinning, osteotomy) or spinal fusion for scoliosis.

Dental Problems: Dentures or implants in adulthood; emphasis on oral hygiene due to high caries risk.

Feeding/Growth: Nutritional support, monitoring growth curves specific to MOPDII; avoid overfeeding.

Vascular/Cardiac: MRI/MRA brain scans for aneurysms; blood pressure monitoring; managing heart conditions.

Learning/Development: Occupational/speech therapy, special tools (voice-to-text) for daily tasks. 

Type of Doctor Department : A Pediatrician and Medical Geneticist , Orthopedic Surgeons, Neurologists/Neurosurgeons,Cardiologists,Endocrinologists,and Therapists

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