Stuve-Wiedemann syndrome (STWS)

Stuve-Wiedemann syndrome

Stuve-Wiedemann syndrome (STWS; MIM 601559) is an autosomal recessive, frequently lethal disorder characterized by postnatal short stature, congenital bowing of the long bones and dysautonomia. The bones of the lower extremities are usually more affected than the bones of the upper extremities. The long bones display cortical thickening and an abnormal trabecular pattern. The metaphyses are wide, flared, rarefied and striated. Talipes valgus and contractures of the elbows, knees, fingers and toes have also been described. Infants typically have an expressionless face with pursed lips. Poor feeding, respiratory insufficiency and temperature instability in the form of episodic hyperthermia often lead to death in the first year of life. Survivors have progressive scoliosis due to severe spinal deformities, prominent joints, osteoporosis, and spontaneous fractures. Sucking and swallowing difficulties improve over time however temperature instability (hyper and hypothermia), and decreased corneal and patellar reflexes persist. Although STWS appears to display genetic heterogeneity, mutations in the leukemia inhibitory factor receptor gene (LIFR) have been identified in many patients. This gene encodes one of two components of the LIF receptor. This receptor binds multiple cytokines including leukemia inhibitory factor and induces signaling through the JAK/STAT and MAPK pathways.