Majewski osteodysplastic primordial dwarfism type II (MOPD II): Natural history and clinical findings

Abstract

A description of the clinical features of Majewski osteodysplastic primordial dwarfism type II (MOPD II) is presented based on 58 affected individuals (27 from the literature and 31 previously unreported cases). The remarkable features of MOPD II are: severe intrauterine growth retardation (IUGR), severe postnatal growth retardation; relatively proportionate head size at birth which progresses to true and disproportionate microcephaly; progressive disproportion of the short stature secondary to shortening of the distal and middle segments of the limbs; a progressive bony dysplasia with metaphyseal changes in the limbs; epiphyseal delay; progressive loose-jointedness with occasional dislocation or subluxation of the knees, radial heads, and hips; unusual facial features including a prominent nose, eyes which appear prominent in infancy and early childhood, ears which are proportionate, mildly dysplastic and usually missing the lobule; a high squeaky voice; abnormally, small, and often dysplastic or missing dentition; a pleasant, outgoing, sociable personality; and autosomal recessive inheritance. Far-sightedness, scoliosis, unusual pigmentation, and truncal obesity often develop with time. Some individuals seem to have increased susceptibility to infections. A number of affected individuals have developed dilation of the CNS arteries variously described as aneurysms and Moya Moya disease. These vascular changes can be life threatening, even in early years because of rupture, CNS hemorrhage, and strokes. There is variability between affected individuals even within the same family.

Mechanisms and pathways of growth failure in primordial dwarfism

“…Formally, therefore, the conditions that we are discussing in this review are ''microcephalic primordial dwarfism.'' Microcephalic primordial dwarfism encompasses several distinct disease entities, including Seckel syndrome (Seckel 1960;Majewski and Goecke 1982), microcephalic osteodysplastic primordial dwarfism (MOPD) types I and II (Majewski et al 1982a,b;Hall et al 2004), and Meier-Gorlin syndrome (MGS) (Gorlin et al 1975;Bongers et al 2001). All are inherited as autosomal recessive traits.…”

“…In this sense, Seckel syndrome is a generic term for microcephalic primordial dwarfism. However, there is substantial variation in usage of this diagnostic term (Al-Dosari et al 2010;Kalay et al 2011), and it has also been used specifically to describe a group of patients with more severe learning disability and a head size disproportionately smaller than their bodies (Goodship et al 2000;Hall et al 2004;Kalay et al 2011). Facial features of a receding forehead, prominent nose, and small chin are said to be present (Majewski and Goecke 1982).…”

“…In contrast, MOPD II is a well-defined and recognizable form of microcephalic dwarfism (Majewski et al 1982a;Hall et al 2004;Rauch 2011). There are characteristic skeletal features as well as distinctive facial features and small loose secondary dentition.…”

Flores hominid: New species or microcephalic dwarf?

“…Under this hypothesis, LB1 would have a short stature with microcephaly syndrome in which both body size and brain volume are far below the norms for the extant population. Various syndromes with severe intrauterine growth retardation and proportionate (at least at birth) microcephaly have been described in modern humans, including Bangstad, Bloom, Buebel, de Lange, Dubowitz, Kennerknecht, Meier-Gorlin, Okajima, and Seckel syndromes, as well as Majewski (microcephalic) osteodysplastic primordial dwarfism (MOPD) type 1, MOPD type 2, MOPD-Cervenka type, and MOPD-Toriello type (Toriello et al, 1986;Bangstad et al, 1989;Opitz and Holt, 1990;Meinecke et al, 1991;Lin et al, 1995;Buebel et al, 1996;Bongers et al, 2001;Silengo et al, 2001;Faivre et al, 2002;Okajima et al, 2002;Hall et al, 2004). Several of these syndromes are associated with survival to adulthood.…”

“…survive to adulthood (Hall et al, 2004). They are remarkably small, with weight, length, and head circumference at birth proportionately reduced to the size of a 28-week gestation fetus.…”