Stiff skin syndrome (SSS) is a rare inherited fibrosing disorder that presents in infancy or early childhood. It is characterized by stone-hard induration of the skin of the buttocks and thighs and less frequently of the shoulder girdle, trunk, and more distal parts of the extremities with subsequent limited joint mobility with flexion contractures. Mild hypertrichosis and mild hyperpigmentation of involved skin may also be seen. Lumbar lordosis, scoliosis, a tiptoe gait, and short stature are frequently observed. Restrictive pulmonary function, nerve entrapment secondary to associated nodules that overlie joints, and ophthalmoplegia are rarely reported.

SSS may be familial and inherited. In the reported kindreds with SSS, the disorder is inherited in an autosomal dominant manner and mutations in the fibrilllin-1 (FBN1) gene have been identified. This mutation leads to excessive microfibrillar deposition, impaired elastogenesis, and increased TGF-β signaling in the dermis. Subsequent molecular analysis of patient-derived dermal fibroblasts has further demonstrated increased pro-fibrotic gene expression and reduced MMP2 activity, contributing to the sclerotic changes characteristic of the disease. 

A segmental variant has also been characterized. This variant has been described as having a unilateral predominance, a later onset, and less functional impairment. It affects females more frequently. The FBN1 mutation has not been detected in segmental variants, leading experts to suspect it could be due to a mosaic mutation.

SSS is typically progressive throughout childhood / adolescence, with stabilization in early adulthood. In segmental variants, skin thickening is limited to the affected body segment; if new lesions develop beyond the original distribution, the widespread variant should be considered.