Overview of genetic testing in Prader-Willi syndrome

ABSTRACT

Introduction

Prader-Willi syndrome (PWS) is a complicated neurodevelopmental genetic disorder stemming from the loss of expression of imprinted genes within the 15q11-q13 region. It is characterized by impaired hypothalamic development and function. Infants with PWS typically present hypotonia and feeding difficulties, which in later stages of childhood progress to hyperphagia, obesity, and endocrine dysfunctions. However, early diagnosis and treatment have proven effective in mitigating obesity and related co-morbidities in patients with PWS. Moreover, the precise molecular classification of PWS is crucial to tailor the appropriate treatment strategies and provide valuable genetic counseling.

Areas covered

This review contains various conventional and novel PWS diagnostic methods, assessing each method’s underlying mechanisms, advantages and disadvantages. Furthermore, our review presents a genetic testing workflow for PWS diagnosis and explores promising techniques for newborn and prenatal screening, which facilitate early diagnosis and intervention. This review synthesizes pertinent studies from 1990 to 2022, gathered from databases including PubMed, Web of Science, EBSCO, and Cochrane.

Expert opinion

Starting with MS-MLPA is the most efficient way to detect underlying genetic mechanisms. However, it is essential to note that certain rare instances, such as balanced chromosomal rearrangements, may require complementary diagnostic techniques to identify accurately.

KEYWORDS:

• Prader-Willi syndrome
• diagnostic testing
• newborn screening
• prenatal screening
• clinical diagnosis

Article highlights

• The importance of early diagnosis and treatment for Prader-Willi Syndrome.

• Advantages and disadvantages of each method.

• Genetic testing strategies for Prader-Willi syndrome.

• Prenatal and newborn screening is a promising prospect to be further studied.

• Measuring the expression of sno-lncRNAs in the blood is a novel tool to screen or diagnose PWS

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or material discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or mending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Authors’ contributions

CCZ conceptualized and designed the study and reviewed and revised the manuscript. YG drafted the initial manuscript. MLZ, YLD, and YHJ collected and reviewed the information about PWS diagnosis. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Additional information

Funding

This work was supported by the National Natural Science Foundation (81371215 and 81670786) and Key R & D Projects of Zhejiang Provincial Science and Technology Agency (2021C03094).