Perlman syndrome

Perlman syndrome is a rare congenital overgrowth disorder characterized by fetal macrosomia (large birth weight), bilateral renal hamartomas (Wilms tumor-like growths in the kidneys), nephroblastomatosis, facial dysmorphism, and organomegaly. It was first described by Perlman and colleagues in 1973. The condition affects multiple body systems, most prominently the kidneys, but also involves the face (characteristic features include a round face, deep-set eyes, depressed nasal bridge, and everted upper lip), the endocrine system (with islet cell hyperplasia of the pancreas leading to neonatal hypoglycemia), and the brain (with developmental delay and intellectual disability in survivors). Hepatomegaly and other visceral enlargement are common. Affected infants are often born prematurely and may present with polyhydramnios during pregnancy. Perlman syndrome carries a very high neonatal mortality rate, estimated at over 60%, primarily due to respiratory complications and renal failure. Survivors have a significantly elevated risk of developing Wilms tumor (nephroblastoma), with estimates suggesting the risk may be as high as 30-65%. The syndrome is caused by biallelic loss-of-function mutations in the DIS3L2 gene on chromosome 2q37, which encodes an exoribonuclease involved in RNA degradation and plays a role in cell growth regulation. Due to the high risk of Wilms tumor, surviving children require regular renal surveillance with abdominal ultrasound screening. Treatment is primarily supportive and symptomatic, addressing neonatal hypoglycemia, respiratory difficulties, and renal complications. Wilms tumors, when they develop, are managed with standard oncologic protocols including surgery, chemotherapy, and sometimes radiation therapy. Genetic counseling is recommended for affected families.

Common questions about Perlman syndrome