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A brachymelic primordial disproportionate dwarfism associated with facial dysmorphism and neurologic impairment.
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Microcephalic Osteodysplastic Primordial Dwarfism (MOPD), Type 1, 2, and 3; MOPD 1, 2, and 3; Brachymelic Primordial Dwarfism; Taybi-Linder Syndrome (MOPD 1); Low-Birth-Weight Dwarfism with Skeletal Dysplasia.
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First described in 1967 by Hooshang Taybi, an Iranian-American pediatric radiologist and David Linder, an American pathologist. They described two siblings with dwarfism, skeletal abnormalities, and severe brain malformations.
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Slightly more than 100 cases have been described (∼42 with MOPD 1, ∼60 with MOPD 2, and <5 with MOPD 3).
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Autosomal recessive. Parental consanguinity has been reported for some cases. MOPD 1 is caused by mutations in the RNU4ATAC gene (U4AT-AC small nuclear RNA, a crucial component of the minor spliceosome) on chromosome 2q14.2, MOPD 2 by mutations in the PCNT (Pericentrin) gene on chromosome 21q22.3, and in MOPD 3 the underlying genetic defect is unknown, but is assumed to be the same as for MOPD 1. MOPD Types 1 and 3 basically present with the same clinical spectrum and only subtle variations with regards to craniofacial and cerebral anomalies and radiographic findings (see “skeletal anomalies”), thus the two types are generally considered to be variants of the same disease (MOPD 1/3).
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Based on the clinical and radiographic findings. Genetic molecular testing can be used to confirm the final diagnosis.
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Some of the clinical features like severe pre- and postnatal growth retardation, marked microcephaly and skeletal dysplasia are common to all three types of MOPD, whereas severe brain anomalies with profound developmental delay, ectodermal anomalies, and shortened life expectancy (often <12 months) are typical for MOPD 1/3. Approximately half of all MOPD 1/3 patients die from infectious causes (see below). The reported average life expectancy for MOPD 1/3 varies widely depending on the underlying mutation and is between 10 and 78 months. Cerebral vasculopathy is found in almost 20% of MOPD 2 patients (but has not been reported in MOPD 1/3) and manifests as multiple cerebral aneurysms, tortuous vessels, or ☞Moya-Moya disease, can exacerbate during puberty and may cause life-threatening cerebral hemorrhages and strokes already early in life. Oligohydramnios with severe intrauterine and postnatal growth retardation are almost always present. Facial dysmorphism and neck anomalies include profound microcephaly with already closed anterior fontanelle at birth with possible craniosynostosis, prominent occiput, sloping forehead, low-set and small, dysplastic, posteriorly rotated ears, large protruding eyes, strabismus, big, prominent nose with downturned tip, unilateral choanal atresia, mandibular hypoplasia, micro-/retrognathia, high-arched and narrow palate, multiple, thick labial frenula, widely-spaced teeth, microdontia, hypoplastic or absent roots, enamel hypocalcification, and cavities with early loss of teeth, and short neck. Central nervous ...