Microcephalic osteodysplastic primordial dwarfism type ii: Report of three cases and review

Abstract

We report on three further patients with microcephalic osteodysplastic dwarfism type II. All children have marked intrauterine and postnatal growth failure, microcephaly, and mental and statomotor retardation. They are disproportionately short statured due to short limbs. Characteristic skeletal abnormalities are small iliac wings with flat acetabular angles, coxa vara, V-shaped distal femoral metaphyses, and triangular distal femoral epiphyses, as well as pseudoepiphyses of metacarpals, short first metacarpals, and brachymesophalangy V. At age 3 years, bilateral epiphyseolysis of the femoral heads occurred in case 1. Including our patients, 17 cases have been published so far. We review the clinical picture and the cause.

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III

“…Some evidence indicates that an MOPD I/III locus lies on chromosome 2q [18], but to date, the molecular basis of this disorder has been obscure [3, 20]. In contrast, MOPD II has been definitively linked to mutations in the pericentrin ( PCNT ) gene [26, 28, 36].…”

“…Type II is apparently a distinct disorder [13, 20, 24, 33], but types I and III may be variant manifestations of the same entity (also known as Taybi–Linder cephaloskeletal dysplasia) with likely autosomal recessive inheritance [3, 10, 22, 34, 37]. Common features in MOPD I and III include severe pre- and post-natal growth retardation, microcephaly, and similar distinctive facies, but dwarfism in type I is more disproportionate with short bowed long bones, less dysplastic pelvis, and no medial spurs of the ischial bones.…”

Hands

“…For example, multiple pseudoepiphyses in the phalanges and metacarpals/metatarsals are often seen in cleidocranial dysplasia (OMIM 119600) and multiple epiphyseal dysplasia (OMIM 132400). Multiple pseudoepiphyses at the base of the metacarpals are often found in osteodysplastic primordial dwarfism, type II (OMIM 210720), an autosomal recessive disorder characterized by severe pre-and postnatal growth retardation, microcephaly, facial features resembling those of Seckel syndrome (OMIM 210600), and a constellation of bone anomalies, including mesomelic limb shortening, brachymesophalangy, short 1st metacarpals, V-shaped distal femurs, narrow pelvis, proximal femoral epiphysiolysis, and coxa vara (Majewski et al 1982;Majewski and Goecke 1998;Verloes et al 1987). Impairment of chondrocytic formation and differentiation at the growth plate is a striking histological finding in this condition (Fukuzawa et al 2002).…”

Identification of two novel critical mutations in PCNT gene resulting in microcephalic osteodysplastic primordial dwarfism type II associated with multiple intracranial aneurysms

“…The common clinical features of MOPD II include microcephaly and disproportionate, skeletal dysplasia, and certain facial characteristics (Majewski and Goecke 1998), although the patients may not have severe microcephaly at birth and their intellectual development may apparently be normal (Hall et al 2004;Piane et al 2009;Rauch 2011). Additional clinical manifestations that some patients may exhibit include anemia, bone marrow failure, T-cell clonality, myelodysplasia, acute myeloid leukemia (Lilleyman 1984;Hayani et al 1994;Chanan-Khan et al 2003), thrombocytosis (Moftakhar et al 2010;Unal et al 2014), leukocytosis and thrombocytosis (Verloes et al 1987;Unal et al 2014), and cerebral aneurysms or moyamoya angiopathy (Hall et al 2004;Piane et al 2009).…”