Wiedemann-Rautenstrauch syndrome

Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is an extremely rare genetic disorder characterized by features of premature aging (progeria) that are apparent at birth. The condition affects multiple body systems, including the skin, skeletal system, adipose tissue, and central nervous system. Key clinical features include intrauterine growth restriction, a progeroid facial appearance with a triangular face, prominent scalp veins, sparse hair, a relatively large head with wide fontanelles, and a characteristic pattern of abnormal fat distribution with accumulation in the buttocks and flanks but generalized lipoatrophy elsewhere. Affected individuals typically have natal teeth (teeth present at birth), a small mouth, and a beaked or prominent nose. Additional features include short stature, failure to thrive, skeletal abnormalities, and variable degrees of intellectual disability. Many affected children experience significant feeding difficulties and recurrent infections. The prognosis is generally poor, with many affected individuals dying in infancy or early childhood, although some patients have survived into their teens or beyond. The syndrome is caused by biallelic pathogenic variants in the POLR3A gene, which encodes a subunit of RNA polymerase III, an enzyme critical for the transcription of small non-coding RNAs essential for cell growth and function. There is currently no cure or disease-specific treatment for Wiedemann-Rautenstrauch syndrome. Management is supportive and multidisciplinary, focusing on nutritional support (often requiring gastrostomy tube feeding), monitoring and managing skeletal complications, dental care, and addressing developmental delays through early intervention programs. Regular follow-up with multiple specialists including geneticists, neurologists, endocrinologists, and orthopedists is recommended to optimize quality of life and address complications as they arise.

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