Congenital contractures, edema, hyperkeratosis, and intrauterine growth retardation: A fatal syndrome in hutterite and mennonite kindreds

Abstract

We present clinical findings in infants from three kindreds (two Hutterite and one Mennonite) with an apparently unique, fatal disorder. The major manifestations consist of severe intrauterine growth retardation, congenital contractures, and tense skin which is easily eroded. The skin is tightly drawn over the face, giving an abnormal appearance consisting of a narrow, pinched nose, small mouth, limited jaw mobility, and ectropion (in one). One infant had first-degree hypospadias. Apart from this, there were no organ malformations and the infants did not have hydrops. Histologically, the skin showed hyperkeratosis. It is postulated that this is a tissue dysplasia and that all of the clinical effects are secondary. The disorder appears to be an autosomal recessive trait. The two Hutterite families are from different endogamous subdivisions. They are related as fourth cousins once-removed and fifth cousins in multiple ways through the six nearest common ancestors of all four parents. There are 25 founders (11 couples and three individuals) who are common ancestors. We computed the probability of joint descent of the four alleles in each pair of parents and in a sample of Alberta Hutterite couples, assuming that each of the common founders in turn was the original carrier. For an allele from one particular founder couple, there is a relatively greater probability of identity by descent for each pair of parents than on the average for other couples of the same endogamous subdivision.

Unique disease heritage of the Dutch‐German Mennonite population

“…Interestingly, we have seen the same mutation in a single Hutterite patient [Gibson et al, 2000, personal communication]. Although the Hutterites and Dutch-German Mennonites are distinct genetic isolates, there are rare reports of common autosomal recessive conditions, for example restrictive dermopathy [Lowry et al, 1985]. In Mennonite families with juvenile/adult HOPS, patients are compound heterozygotes for the p.Glu191Lys mutation and p.Gly334Asp mutation [Greenberg et al, 1991[Greenberg et al, , 1993.…”

“…Restrictive dermopathy is a lethal disorder characterized by very tight and easily eroded skin, abnormal facial appearance, severe intrauterine growth restriction, and congenital contractures. One of the initial presentations of this condition in the modern literature reported on four children from Alberta, three Hutterites, and one Mennonite [Lowry et al, 1985]. The Mennonite child was a male born to Kurlan et al [1986] non-consanguineous parents and had the typical features of restrictive dermopathy.…”

Restrictive dermopathy: Report and review

“…The lack of elastic fibers in the thinner dermis causes a rigidity and vulnerability of the skin and impairs fetal Toriello, 1983Toriello, 1983Toriello, 1986Holbrook, 1987Schnur, 1985Schnur, 1985Lowry, 1985Lowry, 1985Lowry, 1985Lowry, 1985Witt, 1986Holbrook, 1987Witt, 1986Holbrook, 1987Gillerot, 1987Mok, 1990Mok, 1990Mok, 1990 Patient number 1 £ 2 £ 3 4 £ 5 6 £ 7 8 9 1 0 £ 11 12 VanHoestenberghe, 1990Pierard-F., 1992Welsh, 1992Welsh, 1992Paige, 1992Bergmann, 1993Dean, 1993Dean, 1993Reed, 1993 Our movement. Structural deformities, seen in restrictive dermopathy and other FADS [Hammond and Donnenfeld, 1995], may be secondary to this intrauterine immobility, as Moessinger [1983] showed.…”

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…137,138 Generalized erythroderma with scaling, and even collodion membranes, have been described in single cases of hypohidrotic ectodermal dysplasia. 139,140 One important differential diagnosis of HI (or severe collodion babies) is lethal restrictive dermopathy, [141][142][143] which is associated with intrauterine growth retardation, congenital contractures, tight skin, and ectropion, but does not develop hyperkeratosis and scaling. Another perinatal lethal syndrome, the Neu-Laxova syndrome, should be considered in neonates with ichthyosis and multiple anomalies, including tight translucent skin similar to that in restrictive dermopathy, abnormal facies with exophthalmos, marked intrauterine growth retardation, limb deformities, and central nervous system anomalies.…”