Skip to main content

Conference Program

Subpage Hero

Loading

Rare Adult Case of Stüve-Wiedemann Syndrome

Clinical Genetics and Therapeutics
  • Primary Categories:
    • Clinical-Adult
  • Secondary Categories:
    • Clinical-Adult & Pediatric
Introduction
Stüve-Wiedemann Syndrome (SWS), also known as leukemia inhibitory factor receptor (LIFR)-related skeletal dysplasia, is a rare autosomal recessive skeletal dysplasia that is often lethal in the neonatal and infancy periods. Clinical features of SWS are well described and include feeding and respiratory difficulties in infancy, bowed long bones, prominent joints, progressive scoliosis, recurrent spontaneous fractures, joint restrictions, poor dentition, dysautonomia, and possible increased risk of malignant hyperthermia; however, current literature is largely limited to children with SWS, and there is little information available about additional features or management of SWS in adults. We present a case report of a 35-year-old female with SWS, one of the few documented adults with SWS.

Case Presentation
She presented to clinic with a prior clinical diagnosis of osteogenesis imperfecta (OI), which was given in childhood based in part on a history of recurrent fractures and blue sclera. She had not had any previous genetic testing. Her current symptoms included heart palpitations, fatigue, difficulty sleeping, temperature dysregulation, dental problems, and bone fragility. On physical exam, she had short stature, blue sclera, and significant loss of range of motion in most bones with fusions in the fingers, toes, and major long bones throughout. Dual-energy x-ray absorptiometry (DEXA) scan showed osteoporosis and deformity of the right hip and left forearm. In infancy, she experienced feeding and breathing difficulties. She reports her symptoms of difficulty with temperature regulation and recurrent fractures have been life-long. Of note, she has had more than 25 surgeries without complications from anesthesia. Her treatment in childhood included bisphosphonate treatments, both orally and via infusion, but had not occurred for many years. She was incidentally identified to have a brain aneurysm at the age of 34.

Diagnostic Workup
Initial genetic testing included an OI and bone fragility panel, which was non-diagnostic and identified a variant of uncertain significance (VUS) in COL1A2 at c.329C>T (p.Pro110Leu). This missense change replaces proline (neutral, non-polar) with leucine (neutral, non-polar) and is not expected to disrupt protein function. Given the non-diagnostic result, whole exome sequencing (WES) was ordered, which identified a homozygous pathogenic variant in LIFR at c.756dup (p.Lys253*), consistent with a diagnosis of SWS.

Treatment and Management
The patient is planned to re-start bisphosphonate treatment, continue following with orthopedic surgery for potential surgical intervention of skeletal abnormalities and fractures, re-establish dental care, and visit a dysautonomia clinic to address her temperature regulation difficulties, heart palpitations, and increased fatigue. Additionally, she is following with neurology for her brain aneurysm.

Outcome and Follow-Up
The patient will be followed for response to bisphosphonate treatment and management of skeletal abnormalities and dysautonomia. 

Discussion
Current literature on SWS emphasizes high mortality in infancy and early childhood due to respiratory failure and/or feeding difficulties. Our patient demonstrates that patients with SWS who survive these complications continue to have autonomic dysregulation into adulthood and may develop additional medical concerns that are not as well documented in the adult population. Available literature on treatment and management of SWS primarily focuses on acute and palliative care, leaving providers limited guidance on medical management for long-term care including orthopedic, neurologic, and pain management interventions.

Conclusion
To our knowledge, our patient is the oldest reported individual in the literature with SWS. An adult diagnosis expands the known clinical presentation of SWS, providing insight into how symptoms evolve over time, enhancing the phenotypic characterization of the syndrome, expanding knowledge on long-term complications, and helping to establish guidelines for medical management for adults. Additionally, it adjusts the known prognosis and may uncover factors that contribute to longer survival, such as possible genotype-phenotype correlation. Future areas of research include identifying and managing age-related complications and developing treatment and management recommendations for adults with SWS.

Agenda

Sponsors