Clinical Report: Novel LIFR Variant Identified in Stuve-Wiedemann Syndrome

Overview

This report details a case of a 5-month-old infant diagnosed with Stüve-Wiedemann syndrome due to a novel homozygous nonsense variant in the LIFR gene. The findings underscore the importance of genetic testing in diagnosing this rare disorder characterized by severe dysautonomia and skeletal abnormalities.

Background

Stüve-Wiedemann syndrome is a rare autosomal recessive disorder that leads to significant early-life morbidity and mortality due to its associated dysautonomia and skeletal dysplasia. Understanding the genetic basis of this condition is crucial for accurate diagnosis and management, particularly given its overlap with other skeletal dysplasias. The identification of pathogenic variants in the LIFR gene is essential for distinguishing Stüve-Wiedemann syndrome from similar disorders.

Data Highlights

No numerical data or trial data presented in the article.

Key Findings

• A novel homozygous nonsense variant in the LIFR gene (c.823G>T, p.Glu275Ter) was identified in the patient.
• The infant exhibited classic symptoms of Stüve-Wiedemann syndrome, including bowed long bones and severe dysautonomia.
• Global mortality rate for Stüve-Wiedemann syndrome is reported at 46%, with 42% of deaths occurring within the first two years of life.
• Longer-term survival has been observed in some patients beyond the age of two, indicating a potential decline in mortality risk.
• Molecular confirmation aids in differentiating Stüve-Wiedemann syndrome from other skeletal dysplasias.

Clinical Implications

Healthcare providers should consider genetic testing for infants presenting with symptoms suggestive of Stüve-Wiedemann syndrome to confirm diagnosis and guide management. Early intervention and multidisciplinary support can improve outcomes and quality of life for affected patients.

Conclusion

The identification of a novel LIFR variant in this case highlights the importance of genetic testing in Stüve-Wiedemann syndrome, which can inform clinical management and improve patient outcomes.

Related Resources & Content

1. Hamasharef et al., Clinical Case Reports, 2026 -- Novel LIFR Variant Identified in Stuve-Wiedemann Syndrome
2. Brain — De novo variants disrupt an LDB1-regulated transcriptional network in congenital ventriculomegaly
3. Blood Cancer Journal — Co-occurrence of CSF3R T618I Mutation with Splicing and Epigenetic Gene Alterations and a Novel PIM3 Truncated Fusion in Chronic Neutrophilic Leukemia
4. Acta Neuropathologica — Pediatric Li Fraumeni Syndrome Patients with H3F3A G34R Mutation or MYCN Amplification Presenting Malignant Gliomas
5. Blood Cancer Journal — The Possible Influence of STAG1 Gene Mutations on Genetic Susceptibility to Pediatric Blood Cancers
6. Clinical overview and outcome of the Stuve-Wiedemann syndrome: a systematic review
7. Stüve-Wiedemann syndrome