Wiedemann-Rautenstrauch Syndrome
Wiedemann-Rautenstrauch Syndrome
Wiedemann-Rautenstrauch Syndrome (WRS), also known as Neonatal Progeroid Syndrome, is an extremely rare genetic disorder characterized by an aged appearance at birth, growth delays, and distinctive facial features. It was first described by Wiedemann in 1979 and further characterized by Rautenstrauch and Snigula in 1977.
Key Points:
- Incidence: Extremely rare, with fewer than 60 cases reported worldwide
- Inheritance: Autosomal recessive
- Genetic basis: Mutations in the POLR3A gene
- Characterized by progeroid appearance, intrauterine growth restriction, and postnatal growth failure
- Often associated with severe developmental delay and shortened life expectancy
Clinical Features
Wiedemann-Rautenstrauch Syndrome presents with a wide range of clinical features, typically apparent at birth:
Craniofacial Features:
- Large, wide-open fontanelles and sutures
- Prominent scalp veins
- Sparse or absent scalp hair, eyebrows, and eyelashes
- Prominent eyes with a lack of subcutaneous fat around the eyes
- Small, pinched nose
- Small mouth with thin lips
- Micrognathia (small jaw)
- Pseudohydrocephalic appearance
Growth and Development:
- Intrauterine growth restriction
- Severe postnatal growth failure
- Developmental delay and intellectual disability
- Delayed or absent psychomotor development
Skeletal Abnormalities:
- Osteoporosis
- Delayed bone age
- Hip dysplasia
- Thin, long bones
Other Features:
- Lipodystrophy (lack of subcutaneous fat)
- Wrinkled, thin skin giving an aged appearance
- Natal teeth (teeth present at birth)
- Feeding difficulties
- Cardiovascular anomalies
- Genital abnormalities (e.g., cryptorchidism in males)
- Hepatomegaly
- Hypertrichosis (excessive hair growth) on extremities
Diagnosis
Diagnosis of Wiedemann-Rautenstrauch Syndrome is based on clinical features and genetic testing:
Clinical Diagnosis:
- Presence of characteristic facial features
- Progeroid appearance at birth
- Severe growth retardation
- Lipodystrophy
- Large fontanelles and prominent scalp veins
Genetic Testing:
- Molecular genetic testing for mutations in the POLR3A gene
- Sequence analysis and deletion/duplication analysis
Differential Diagnosis:
Consider other progeroid syndromes, such as:
- Hutchinson-Gilford Progeria Syndrome
- Nestor-Guillermo Progeria Syndrome
- Marfan Syndrome with Neonatal Progeroid Syndrome-like lipodystrophy
Prenatal Diagnosis:
- Possible through molecular genetic testing if familial mutations are known
- Prenatal ultrasound may detect intrauterine growth restriction and some facial features
Management
Management of Wiedemann-Rautenstrauch Syndrome is supportive and focuses on addressing specific symptoms:
Multidisciplinary Care:
- Coordinated care involving geneticists, pediatricians, neurologists, and other specialists
Nutritional Support:
- Aggressive nutritional support to promote growth
- Gastrostomy tube placement for severe feeding difficulties
- Monitoring of growth and nutritional status
Developmental Support:
- Early intervention programs
- Physical therapy to improve motor skills
- Occupational therapy for daily living skills
- Speech and language therapy
Management of Specific Issues:
- Regular dental care for natal teeth and dental anomalies
- Ophthalmological evaluation and management
- Monitoring and treatment of cardiovascular issues
- Management of respiratory infections
- Skin care to prevent infections and manage dermatological issues
Psychosocial Support:
- Genetic counseling for families
- Psychological support for patients and caregivers
Genetics
Genetic Basis:
- Caused by biallelic mutations in the POLR3A gene located on chromosome 10q22.3
- POLR3A gene encodes the largest subunit of RNA polymerase III
- RNA polymerase III is crucial for transcription of transfer RNAs and other small RNAs
Inheritance Pattern:
- Autosomal recessive inheritance
- Parents are typically asymptomatic carriers
- 25% chance of affected offspring when both parents are carriers
Genotype-Phenotype Correlation:
- Limited information due to the rarity of the condition
- Severity may vary even among siblings with the same mutations
- Some POLR3A mutations are associated with other disorders (e.g., 4H leukodystrophy)
Genetic Counseling:
- Offer carrier testing for at-risk relatives
- Discuss prenatal testing options for future pregnancies
- Preimplantation genetic diagnosis may be available
