Summary
Microcephalic osteodysplastic primordial dwarfism (MOPD) types 1 and 3 are characterized by intrauterine and postnatal growth retardation, microcephaly, facial dysmorphism, skeletal dysplasia, low-birth weight and brain anomalies. Although MOPD types 1 and 3 were originally described as two separate entities on the basis of radiological criteria (notably small differences in pelvic and long bone structure), later reports confirmed that the two forms represent different modes of expression of the same syndrome. The prevalence is unknown but less than 30 cases have been described in the literature so far. The facial dysmorphism is characterized by a prominent nose with a flat nasal bridge, protruding eyes, a sloping forehead, and micrognathia. Sparse hair and eyebrows, dry skin, short limbs and dislocation of the hips and elbows are other common features. The most frequent neurological manifestations are seizures and intellectual deficit, and reported brain anomalies include lissencephaly, hypoplastic frontal lobes, and agenesis of the corpus callosum or cerebellar vermis. MOPD types 1 and 3 are transmitted as autosomal recessive traits and although the causative gene remains unknown, homozygosity mapping has allowed identification of a candidate gene region on chromosome 2q (2q14.2-q14.3). Histological studies suggest that MOPD types 1 and 3 result from a basic defect in cell proliferation and tissue differentiation. Diagnosis is made on the basis of the clinical and radiological phenotype, with common radiological features including short tubular bones, enlarged metaphyses, vertebral and pelvic anomalies, elongated clavicles, bowing of the long bones and cleft vertebral arches. The differential diagnosis should include MOPD type 2 (see this term) and other syndromes associated with primordial dwarfism (such as Seckel syndrome; see this term). Prenatal diagnosis, by ultrasonography at around 20 weeks of gestation, has been reported in affected families. Treatment is supportive only. The prognosis is poor with most of the reported patients dying within the first year of life. *Author: Orphanet (November 2008)*.
