Another Italian family with mandibuloacral dysplasia: Why does it seem more frequent in Italy?

Abstract

We describe three patients (one female and two males in a sibship of 11) with mandibuloacral dysplasia. Only eight families have been reported previously, and of these, four were of Italian origin. The phenotypic spectrum of the condition is delineated and its variability is stressed. The observation of three affected members of both sexes with normal parents supports the hypothesis of autosomal recessive inheritance. The reasons for the high frequency of the condition in Italy are discussed; a local selective advantage for heterozygotes and founder effect might be involved.

Familial mandibuloacral dysplasia: Report of an additional Italian patient

“…Five of the 11 MAD known families are of Italian ancestry. One patient was born in the Northeast region, whereas four originated from a sparsely populated area in central Italy [Tenconi et al, 1986]. Our family was originating also from central Italy, notably from the same region (Latium, 17,200 sq km) in which other patients were born, supporting the existence of a founder effect.…”

“…Additional features are short stature, multiple wormian bones, prominent eyes, and sharp nose [Danks et al, 1974; Welsh, 1975], although occasional findings include highly arched palate, increased subcutaneous fat on the trunk, cortical long bones sclerosis, scoliosis, deformed medial condyles, and delayed puberty [Young et al, 1971; Cohen et al, 1973; Danks et al, 1974; Pallotta and Morgese, 1984; Parkash et al, 1990; Friedenberg et al, 1992]. Five of the 11 reported families were of Italian origin, suggesting a common ancestor(s) [Tenconi et al, 1986]. However, consanguinity was proved only in one of these families [Zina et al, 1981].…”

Maxillofacial and Dental Manifestations in a Patient with Mandibulo-Acral Dysplasia

“…Cusano, et al 13 examined 26 patients with MAD and reported that 22 of them had mandibular hypoplasia, whereas SchranderStumpel, et al 4 reported 20 of 21, and Tenconi, et al 10 reported 16 of 18 had mandibular hypoplasia. The two cases with the most extensive mandibular defects were reported by Tenconi, et al 10 and Hoeffel, et al 6 Tenconi, et al 10 described a patient displaying a hypoplastic and edentulous mandible but with a complete resorption of the right mandibular ramus. The latter was a 7-year-old girl with MAD, described by Hoeffel, et al, 6 displaying mandibular hypoplasia, absence of the condyles and ramus, and dental abnormalities such as malocclusion and hypodontia.…”

A case of craniomandibular dermatodysostosis associated with focal glomerulosclerosis

“…Previously, patients with this condition had been mistakenly diagnosed as having Werner's syndrome [4], cleidocranial dysplasia [2] or acrogeria [5]. The occurrence of the disorder in siblings strongly suggested autosomal recessive inheritance [6][7][8][9], and it had an apparently high frequency in Italians [61.…”