Predicting homozygous M694V genotype in paediatric FMF: multicentre analysis and scoring system proposal

Area of Science:

• Genetics
• Pediatric Rheumatology
• Rare Diseases

Background:

• Familial Mediterranean Fever (FMF) is a genetic autoinflammatory disorder.
• The M694V variant in the Mediterranean Fever gene is common, particularly in homozygous form.
• Understanding genotype-phenotype correlations is crucial for FMF management.

Purpose of the Study:

• To assess the predictive value of the homozygous M694V genotype in pediatric FMF patients.
• To develop a clinical scoring system for improved FMF disease management.
• To identify clinical predictors associated with the homozygous M694V genotype.

Main Methods:

• Nationwide, multicenter, cross-sectional study of 3,981 pediatric FMF patients.
• Comparison between patients with homozygous M694V genotype and those with other variants.
• Data collected from 37 pediatric rheumatology/nephrology clinics in Türkiye (2014-2023).

Main Results:

• Homozygous M694V genotype associated with earlier symptom onset and diagnosis.
• Increased prevalence of FMF family history in the homozygous M694V group.
• Higher rates of arthritis, erysipelas-like erythema (ELE), protracted febrile myalgia syndrome (PFMS), and colchicine resistance in homozygous M694V patients.
• Key predictors identified: early symptom onset, family history, arthritis, myalgia, PFMS, ELE, and splenomegaly.

Conclusions:

• The homozygous M694V genotype in pediatric FMF has distinct clinical predictors.
• A proposed clinical scoring system can aid in prognosis assessment and treatment planning.
• This tool aims to improve patient outcomes in pediatric FMF.