ESPE Abstracts

Background: Stüve-Wiedemann syndrome (SWS) is a rare autosomal recessive disorder, due to mutations in the leukemia inhibitory factor receptor (LIFR) gene. It is characterized by bowed-long bones, joint restrictions, dysautonomia, respiratory and feeding difficulties leading to death during infancy. In SWS survivors beyond 2 years of age, orthopedic problems are the main concern e.g. spinal deformations, osteoporosis and recurrent spontaneous fractures which affects quality of life (QoL). This occurs mainly due to excessive osteoclastic resorption. Delayed motor development has been reported in all SWS patients, however, cognitive development is normal in all but one of the reported cases. There is no specific treatment for SWS, and management is symptomatic. Limited number of cases have been reported so far, making it more difficult to understand the disease pathology. We herein report a 5-year-old boy diagnosed with SWS and cognitive impairment at Alexandria University Children’s hospital.

Case summary: A 5-year-old-boy presented with history of recurrent fractures in different long bones. He is the only child born to consanguineous parents. After birth, limb deformity was noticed and he was hypoactive. Skeletal survey showed bowing of lower limbs with no signs of active rickets and hip ultrasonography revealed delayed and defective ossification of both acetabular fossae with bowing of the metadiaphysis bilaterally, associated with lateral subluxation of both femoral head cartilaginous epiphysis suspecting osteogenesis imperfecta. CT brain showed subependymal hemorrhage involving lateral ventricles with mildly dilated ventricular system. Audiometry showed bilateral normal hearing. He had delayed developmental milestones and was diagnosed with intellectual disability and autistic features. EMG, NCV were normal. Bowing of lower limbs progressed and he developed joint mobility restriction in knees and fingers. He presented with faltering growth, facial dysmorphism (squared face, low-set ears), and limb deformities. He had no history of hyperthermic episodes or limited sensation. There was no blue sclera. Calcium, phosphorus, magnesium, 25-OHD, 1,25-dihydroxyvitamin D, and PTH levels were normal. Dual x-ray absorptiometry height-for-age Z-score did not show low bone mineral density. WES identified a novel homozygous pathogenic variant in LIFR (c.703_704del, p.Trp235GlufsTer2) causing SWS.

Conclusion: SWS is a rare and lethal condition due to mutation in LIFR gene. Diagnostic criteria include the association of short, bowed-long bones, and dysautonomia with normal cognitive development. However, not all patients present similarly. More collaborations and research are required for better description and understanding of the disease, paving the road towards finding novel therapies to improve QoL of SWS survivors.