Wiedemann-Rautenstrauch Syndrome- New Pathways for an Old Disease

Wiedemann-Rautenstrauch Syndrome (WRS), is a rare neonatal progeroid condition. It is characterized by prenatal and postnatal growth retardation, with characteristic physical findings.

We present two affected male siblings, born to a Persian Jewish non-consanguineous couple. The elder sibling is currently 19 y.o and presents with severe growth retardation, weight 11.7kg (-22SD) with extreme lipodystrophy. His pregnancy was significant for IUGR notable from 28 weeks and a single umbilical artery.

The second child’s prenatal findings included IUGR along with an abnormal large skull, widely spaced occipital sutures, flat nasal bone with a striking triangular appearance of the mandibular and maxillary alveolar ridges. Prenatal ultrasonographic diagnosis and genetic counseling were provided, and parents decided to pursue the pregnancy. At the time of the second child’s pregnancy the disease-causing gene was not identified.

This child is currently 3.5 years old, weighs 6.2kg (-9SD) with physical features consistent with WRS. The striking growth retardation shared by both siblings led to numerous feeding attempts, and PEG insertion was proposed but declined by the family. The children’s failure to thrive caused extreme parental anxiety. Despite high calorie, continuous NG tube feeds, the children didn’t gain weight, suggesting a unique metabolic disturbance of an unknown mechanism, which is an inherent part of their disease.

Whole exome sequencing revealed the causative mutations in both siblings, found to be compound heterozygous for two maternally inherited, intronic mutations and a paternally inherited missense mutation in POLR3A gene. Identification of the causative mutations, enabled to design and offer preimplantation testing for the family, and mother is currently under treatment.