Prader-Willi Syndrome - Clinical Genetics, Diagnosis and Treatment Approaches: An Update

Abstract

Background: Prader-Willi Syndrome (PWS) is a neurodevelopmental genomic imprinting disorder with lack of expression of genes inherited from the paternal chromosome 15q11-q13 region usually from paternal 15q11-q13 deletions (about 60%) or maternal uniparental disomy 15 or both 15s from the mother (about 35%). An imprinting center controls the expression of imprinted genes in the chromosome 15q11-q13 region. Key findings include infantile hypotonia, a poor suck, failure to thrive and hypogonadism/hypogenitalism. Short stature and small hands/feet due to growth and other hormone deficiencies, hyperphagia and marked obesity occur in early childhood, if uncontrolled. Cognitive and behavioral problems (tantrums, compulsions, compulsive skin picking) are common.

Objective: Hyperphagia and obesity with related complications are major causes of morbidity and mortality in PWS. This report will describe an accurate diagnosis with determination of specific genetic subtypes, appropriate medical management and best practice treatment approaches.

Methods and results: An extensive literature review was undertaken related to genetics, clinical findings and laboratory testing, clinical and behavioral assessments and summary of updated health-related information addressing the importance of early PWS diagnosis and treatment. A searchable, bulleted and formatted list of topics is provided utilizing a Table of Contents approach for the clinical practitioner.

Conclusion: Physicians and other health care providers can use this review with clinical, genetic and treatment summaries divided into sections pertinent in the context of clinical practice. Frequently asked questions by clinicians, families and other interested participants or providers will be addressed.

Keywords: Diagnostic protocols; Prader-Willi syndrome; caloric intake; care management; genetic testing; genomic imprinting; medication; obesity; treatment approaches..

Fig. (1)

(a). Facial and torso view of a 9 month-old female with Prader-Willi syndrome due to a 15q11-q13 deletion. Note the narrow bifrontal diameter, almond-shaped eyes, a flaccid appearing face, down-turned corners of the mouth, a small chin and short neck frequently seen in PWS infants. A gastrostomy feeding site is observed in the upper abdomen. (b). Frontal body view of the infant female with Prader-Willi syndrome. Note generalized hypotonia and gastrostomy site related to a poor suck, hypotonia and feeding difficulties.

Fig. (2)

(A). Facial view of a 16 year-old female with Prader-Willi syndrome due to maternal disomy 15 without growth hormone treatment. Note slightly upward slant of almond-shaped eyes, a short nose and short neck with obesity. (B). Frontal view of face and torso of the 16 year-old female with Prader-Willi syndrome showing characteristic facial findings, central obesity and self-injury sites on right hand and wrist. (C). Full body profile of the 16 year-old female with Prader-Willi syndrome showing obesity and small hands commonly seen in this obesity-related genetic disorder.