Prader-Willi Syndrome

Objectives

After completing this article, readers should be able to:

1. Recognize Prader-Willi syndrome in the neonate.

2. Recognize the hallmarks of disorders due to imprinted genes.

3. Interpret the results of diagnostic testing.

4. Initiate appropriate management to avoid long-term sequelae of massive obesity.

5. Explain the risks and benefits of growth hormone treatment in Prader-Willi syndrome.

Introduction

Prader-Willi syndrome (PWS) is one of the better known genetic syndromes, mostly because of the striking phenotype in older children of massive obesity, hyperphagia, and severe behavior problems, often involving food. Clinicians have recognized for some time that early diagnosis, during the equally striking neonatal hypotonic phase of the disorder, allows for a head start in the management and the avoidance of many of the eating and behavior problems that occur in unmanaged disease. Neonatologists and pediatric neurologists have greatly developed their skills in diagnosing PWS, leading to substantial improvements in the lives of affected children and their families. This is a true success story. This review describes both the neonatal and the later phenotype of PWS, examines the differential diagnosis, discusses current therapy for the disorder, examines the molecular and biologic bases for the disorder, and reviews the tests used to confirm the diagnosis.

Clinical Description

PWS initially was described in 1956 in children who had short stature, obesity, and mental retardation. Later, it became the first recognized disorder caused by a microdeletion of a chromosome and one of the first examples of a disorder of genomic imprinting. The incidence of PWS is about 1 in 10,000 to 15,000 live births, with no particular geographic or ethnic predilection. Most cases occur sporadically, although rare cases due to primary defects of the imprinting mechanism or resulting from familial translocations involving chromosome 15 may recur.

Neonatal Features and Evaluation

The clinical phenotype of PWS has two distinct phases: the “neonatal hypotonia” phase and the later …