Phenotypic heterogeneity within twins with MELAS with epilepsy: Case report

Area of Science:

• Genetics
• Neurology
• Mitochondrial Biology

Background:

• Mitochondrial encephalomyopathy with lactic acidemia and stroke-like episodes (MELAS) is a maternally inherited mitochondrial disorder.
• It is commonly caused by the m.3243A>G mutation, impairing oxidative phosphorylation and energy production.
• This energy deficit particularly affects high-demand tissues like the brain and muscles, leading to neurological and muscular dysfunction.

Purpose of the Study:

• To report a case of twin brothers diagnosed with MELAS syndrome.
• To highlight the phenotypic heterogeneity and diagnostic challenges associated with MELAS.
• To emphasize the importance of early genetic testing and family screening for MELAS.

Main Methods:

• Clinical evaluation of twin brothers presenting with heterogeneous neurological and multisystemic symptoms.
• Diagnostic tools included electroencephalography (EEG) and cranial magnetic resonance imaging (MRI).
• Genetic testing confirmed the m.3243A>G mutation in both twins and identified the mother as an asymptomatic carrier.

Main Results:

• Both twin brothers were definitively diagnosed with MELAS syndrome.
• The elder twin presented with seizures, learning difficulties, and exercise intolerance; the younger twin developed hearing loss and epileptic seizures.
• The case demonstrated the progressive and variable nature of MELAS manifestations.

Conclusions:

• MELAS syndrome exhibits significant phenotypic heterogeneity, often leading to misdiagnosis or delayed diagnosis.
• Early genetic testing is critical for accurate identification and prompt intervention in suspected MELAS cases.
• Family screening is recommended due to maternal inheritance, and management should be tailored to individual clinical presentations.