Severe congenital limb deficiencies, vertebral hypersegmentation, absent thymus and mirror polydactyly: A defect expression of a developmental control gene?

Abstract

We describe two unrelated patients with a complex malformation pattern that may be a candidate for a developmental gene disorder. These two patients had severe, symmetrical upper and lower limb deficiencies, vertebral hypersegmentation, and duodenal atresia. Patient 1 also had mirror-image polydactyly of his feet; patient 2 was athymic. The concurrence in two unrelated patients of additional vertebrae with severe anomalies in limb development, including a symmetrical deficiency of the four limbs and either mirror-image duplication of some toes (only in patient 1) or absence of the thymus (only in patient 2), represents an early alteration in body-plan organization. Since limb development, thymus development and segmentation are possibly under the control of homeobox genes in the human embryo, it seems reasonable that the malformations observed in these two patients resulted from a defect of a gene controlling developmental pattern formation, possibly a homeobox gene or a paired-box gene. Severe limb deficiencies have been reported in other well-known genetic entities, such as Roberts syndrome, Baller-Gerold syndrome, X-linked amelia, and DK-phocomelia syndrome. However, since the specific pattern of anomalies observed in these patients makes the diagnosis of some of the abovementioned disorders unlikely, we conclude that our patients have a previously undescribed disorder.

Severe limb deficiencies, vertebral hypersegmentation, and mirror polydactyly: Two additional cases that expand the phenotype to a more generalized effect on blastogenesis

“…These 2 cases presented with severe limb deficiencies, vertebral and rib defects, mirror polydactyly, and other blastogenetic defects mostly affecting the midline. These fetuses may have the same condition that was previously described by us [Urioste et al, 1996] in another two cases from the ECEMC, although with a more severe MCA pattern (Table I). Because these 4 cases were identified in a series of consecutive births, the prevalence figure is 3.0/1,000,000 live births in our population.…”

“…As we commented in our previous publication [Urioste et al, 1996], several of the manifestations of these patients were observed previously to be the consequence of alteration in the expression of a homeotic gene in humans or in vertebrates. Homeotic genes are involved in positional information for cellular populations [Hunt and Krumlauf, 1991;Pierpont and Erickson, 1993].…”

“…Recently we [Urioste et al, 1996] described 2 unrelated infants with a multiple congenital anomalies (MCA) pattern composed of severe congenital limb deficiencies, vertebral hypersegmentation, absent thymus, and mirror polydactyly. We speculated that these cases were produced by defective expression of a developmental control gene.…”

Mirror foot: Treatment of three cases and review of the literature

“…In addition, mirror hands typically had seven or eight digits and no thumb, while mirror feet were more variable, ranging from five to ten toes [17]. No tibia and fibula 1 [22] Some of the mirror feet had central hallux with or without bony fusion, and others had no obvious hallux [13,21]. In our three cases, the numbers of toes were seven or eight.…”

Amelia: Analysis of its epidemiological and clinical characteristics

“…Although amelia is not considered as being of genetic origin [Lenz, 1980], there are several genetic conditions that present with amelia [Froster-Iskenius and Baird, 1990]. Recently, we published 2 unrelated cases with severe limb deficiencies (including amelia) and vertebral hypersegmentation, absent thymus, and mirror polydactyly whose parents were consanguineous [Urioste et al, 1996]. In our 18 cases with amelia, 2 had this new syndrome; another had cleft lip and palate, and we suspected Roberts syndrome although chromosome analysis was not performed.…”