Multi-locus imprinting disturbance (MLID): interim joint statement for clinical and molecular diagnosis

Area of Science:

• Genetics
• Epigenetics
• Rare Diseases

Background:

• Imprinting disorders arise from altered gene expression due to epigenetic regulation, specifically DNA methylation.
• Multi-locus imprinting disturbance (MLID) involves methylation changes at multiple imprinted loci, impacting diagnosis and prognosis.
• Existing guidelines lack consensus on MLID definition, testing, and management, creating an unmet need.

Purpose of the Study:

• To establish consensus and provide interim guidance for the clinical and molecular diagnosis of MLID.
• To address the lack of standardized approaches in imprinting disorder management.
• To cover the unmet need for clear protocols regarding MLID.

Main Methods:

• A comprehensive literature search identified over 100 relevant articles.
• Two working groups focused on clinical diagnosis and molecular testing, comprising 31 experts from 11 countries.
• Discussions and a face-to-face meeting with patient advocacy representatives informed the guidance.

Main Results:

• 16 propositions and 8 recommendations were formulated based on expert consensus and available evidence.
• These provide interim guidance for both clinical and molecular diagnosis of MLID.
• The findings aim to standardize the approach to MLID.

Conclusions:

• MLID is a molecular designation; 'multi-locus imprinting syndrome' is proposed for patients with atypical phenotypes.
• Expert collaboration across disciplines is crucial for accurate diagnosis, counseling, and care.
• Global research efforts are advocated to address knowledge gaps, with a planned update in 3-5 years.