Stiff Skin Syndrome is Highly Heterogeneous, and Congenital Fascial Dystrophy is its Distinct Subset

Stiff skin syndrome (SSS), described by Esterly and McKusick in 1971 (1), caused considerable interest, since hereditary scleroderma-like cutaneous changes with contractures and no abnormal mucopolysaccharide metabolism appeared to be a novel entity, and cases of this type have been reported under various names. All four patients of these authors had similar clinical features: pronounced induration of the buttocks and upper thighs, with normal skin of the hands, and no dysmorphic traits. Although in this series there was an affected mother and her two children, the mode of inheritance was difficult to establish since the siblings were the product of a consanguineous marriage. In all patients, histochemical studies disclosed mucopolysaccharides in the skin. In the most affected sporadic patient, large cells in the skin biopsy specimens were stained metachromatically and the cultured skin fibroblasts were packed with great numbers of metachromatic granules (1). The authors suggested a possible localized connective tissue disorder with mucopolysaccharide deposits in the skin, that is, an abortive variety of mucopolysaccharidosis without mucopolysacchariduria. Since that first description of SSS, numerous reports have appeared of patients with similar scleroderma-like presentations and highly variable clinical features and course, some with deposition of mucopolysaccharides in the skin without mucopolysacchariduria (2). However, under this name were also described quite different, lethal cases, such as the child with ainhum-like constriction rings at the ankles, severe osteoporosis, and total osteolysis of the clavicules and distal phalanges, with no mucopolysaccharide deposits and no fascia abnormality. Restriction of the chest and costal mobility led to death at the age of 22 months (3). Also proposed as SSS was an infant with cutaneous stiffness since birth with flexion contractures, no mucopolysacchariduria, no mucopolysaccharides in the fibroblast cultures, but some hyaluronic acid depositions throughout the dermis and fascia. This infant also had osteoporosis of the hands and feet, hypoplasia of the clavicules, and epiphysis of the humerus, muscle and bone involvement, and many other abnormalities, and died from respiratory failure (4). The authors asked the question whether their patient could be the first instance of SSS with visceral involvement. It should be stressed, however, that scleroderma-like conditions in early infancy with flexion contractures might be due to diverse causes; in these two patients it could be a fatal form of neonatal progeria (5,6) or a progerioid sclerodermiform syndrome (7). SSS has also been described as various genetic disorders with dysmorphic features (8), for example, as Parana familial cases with visceral involvement (9), geleophysic dysplasia (10), and others, which should not be included in the syndrome described by Esterly and McKusick as SSS (i.e., an abortive form of mucopolysaccharidosis limited to the skin, with scleroderma-like cutaneous changes and flexion contractures, without visceral and musculoskeletal involvement). We have described changes apparently belonging to this syndrome, but with no mucopolysaccharide deposits in the skin and with exclusive involvement of the fascia (11–13). The clinical distribution of the induration, most