Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is an extremely rare inherited genetic condition. It is characterized by features suggesting premature aging, evident at birth. With fewer than 100 affected individuals described in medical literature, WRS impacts various bodily systems, leading to distinctive physical characteristics and developmental challenges from early life.
Physical and Developmental Characteristics
Infants with WRS often present with a distinctive appearance, including features of aging at birth and significant growth delays that begin before birth and continue after. A noticeable characteristic is the lack of fatty tissue under the skin, known as subcutaneous lipoatrophy, which contributes to a gaunt look, particularly in the face, arms, and legs. This absence of fat can also make the skin appear thin and translucent.
Facial features often appear triangular, with a prominent forehead and a pointed chin. Affected individuals may have sparse hair on the scalp, eyebrows, and eyelashes, along with prominent veins, especially visible on the scalp. Common facial traits also include a small mouth, sometimes with a thin upper lip, and a beaked nose. The skull bones may have widely open spaces (fontanelles), which typically close in early childhood but can remain open in individuals with WRS.
WRS is associated with low birth weight and continued growth retardation. Many affected infants are born with natal teeth, which usually fall out within weeks. Some individuals may also experience hypodontia, where permanent teeth do not develop. Developmental delays, particularly in psychomotor skills, are common, and mild to moderate intellectual disability can also occur.
As individuals with WRS age, they may develop joint contractures that restrict movement. Movement problems, including difficulty with coordination and balance (ataxia) or involuntary rhythmic shaking (tremor), can also progress over time. Some individuals may also experience vision or hearing impairments.
Genetic Origins of the Syndrome
Wiedemann-Rautenstrauch syndrome is a genetic disorder caused by variants in the POLR3A gene. This gene is located on the long arm of chromosome 10 at position 10q22.3. The POLR3A gene provides instructions for creating the largest subunit of the enzyme RNA polymerase III.
RNA polymerase III is involved in the production of various forms of RNA, which are molecules essential for assembling proteins. This process is fundamental for the normal functioning and survival of cells throughout the body. Variants in the POLR3A gene that lead to WRS result in the production of abnormal subunit proteins, which can hinder the proper assembly or function of the RNA polymerase III enzyme.
The condition follows an autosomal recessive inheritance pattern. This means an individual must inherit two altered copies of the POLR3A gene, one from each parent, to develop the syndrome. The parents of an affected individual each carry one copy of the altered gene but do not show any signs or symptoms of the condition themselves.
The Diagnostic Process
The identification of Wiedemann-Rautenstrauch syndrome often begins with clinical observation of distinct physical characteristics present at birth or shortly thereafter. Healthcare providers may suspect WRS based on the combination of premature aging features, growth delays, and specific facial and bodily traits. This initial assessment considers the child’s overall presentation.
To confirm a suspected diagnosis, molecular genetic testing is performed to identify variants in the POLR3A gene. This analysis examines the child’s DNA to pinpoint the changes known to cause WRS. Genetic testing helps differentiate WRS from other conditions with similar progeroid features, such as Hutchinson-Gilford progeria syndrome or Marfan lipodystrophy syndrome. Reliable prenatal diagnosis is also possible if a pathogenic variant has been identified in a family member previously.
Managing Health and Development
There is currently no specific cure for Wiedemann-Rautenstrauch syndrome, so management focuses on supportive care and addressing symptoms as they arise. A multidisciplinary healthcare team is involved in providing comprehensive care for individuals with WRS. This team may include pediatricians, geneticists, and various specialists to manage health challenges.
Nutritional support is frequently needed to address severe feeding difficulties and support growth, as individuals with WRS often experience failure to thrive. Physical and occupational therapists address developmental delays and help improve motor skills and overall function. Dental specialists and craniofacial teams manage dental anomalies like natal teeth and other facial structural concerns.
While many individuals with WRS do not survive past infancy or early childhood, some have lived into their teens or twenties with supportive care. Management aims to maximize quality of life for affected individuals through ongoing monitoring and interventions tailored to their specific needs. Genetic counseling is offered to families to explain the autosomal recessive inheritance pattern and the 25% recurrence risk for future pregnancies.