ESPE Abstracts

Introduction: Wiedemann-Rautenstrauch syndrome (WRS). or neonatal progeroid syndrome, is an orphan hereditary disease associated predominantly with bi-allelic mutations in the POLR3A, POLR3B, and POLR3GL genes and characterized by congenital lipodystrophy, progeroid facial features, and premature aging. Unlike Hutchinson-Gilford progeria, the clinical features of the syndrome are evident at birth. The prevalence of the disease is unknown; 19 proven clinical cases are described in the literature. The average life expectancy of patients is 7 months – 2 years. Patients most often die from sepsis caused by aspiration or bacterial pneumonia. There is no pathogenic treatment for the syndrome.

Materials and Methods: A 6-years-4-months-old girl with WRS, observed in the pediatric endocrinology department of the Sechenov Center for Maternity and Childhood, Moscow. The diagnosis was confirmed by full-exome sequencing.

Results: A girl from healthy unrelated parents, born from the 1st pregnancy, complicated with delayed intrauterine development, meningocele, and fetoplacental insufficiency from the 30th week of gestation. Delivery by Caesarean section at 37 weeks. Birth length 46 cm (SDS -2.20), birth weight 1840 g (SDS -4.27); born with noticeable absence of subcutaneous fat, hydrocephalic skull with prominent venous network in all regions, micrognathia, neonatal incisor of maxilla which fell out on its own on the second day of life. At 2 years, she was first examined by geneticist, progeria was suspected. At 6 years 4 months she was examined at the pediatric endocrinology department: height 99 cm (SDS -3.14), weight 10 kg (BMI 10.20 kg/m2, SDS -5.49); progeroid facial features; hypotrichosis of the scalp; generalized lipodystrophy with preserved isolated areas of subcutaneous fat in the neck, external genitalia, coccygeal region and foot area; limited mobility of the hip joints and interphalangeal joints of the hands. Multisystemic lesions were revealed: endocrine (stunting, body weight deficiency, lack of subcutaneous fat); sceletal (scoliotic posture disorder, flexion contractures of hip and knee joints, osteoporosis; macrocrania, Arnold-Chiari type 1 anomaly, spina bifida C1); dermatological (irritant dermatitis of hands); cardiovascular (sinus tachycardia); pulmonological (bronchoobstructive syndrome); gastroenterological (chronic constipation); psycho-neurological (dysarthria); ophthalmological (retinal angiopathy, mild degree hyperopia, astigmatism). Based on the history and phenotype data, WRS was diagnosed; compound heterozygous mutation c.3337-11T>C/c.3677T>C in the POLR3A gene was detected.

Conclusions: The presented clinical case expands our knowledge of premature aging syndromes. Early diagnostics of the disease allows differential diagnosis with other progeroid syndromes and determination of the optimal management plan for patients by a multidisciplinary team.