Differential diagnosis
The presentation of some cases is similar to that of Kearns–Sayre syndrome.Myoclonus epilepsy associated with ragged red fibers (MERRF) may be confused with MELAS as they both involve seizures, mental deterioration, and myopathy with ragged red fibers on biopsy. MERRF patients may also have hearing loss, visual disturbance secondary to optic atrophy, and short stature. The characteristic myoclonic seizure in MERRF may help to narrow diagnosis, but genetic testing should be considered to distinguish the two conditions.Leigh syndrome may also present with progressive neurological deterioration, seizures, and vomiting mainly in young children. Genetics
MELAS is mostly caused by mutations in the genes in mitochondrial DNA, but it can also be caused by mutations in the nuclear DNA. NADH dehydrogenase
Some of the genes (MT-ND1, MT-ND5) affected in MELAS encode proteins that are part of NADH dehydrogenase (also called complex I) in mitochondria, that helps convert oxygen and simple sugars to energy. Transfer RNAs
Other genes (MT-TH, MT-TL1, and MT-TV) encode mitochondrial specific transfer RNAs (tRNAs).Mutations in MT-TL1 cause more than 80 percent of all cases of MELAS. They impair the ability of mitochondria to make proteins, use oxygen, and produce energy. Researchers have not determined how changes in mitochondrial DNA lead to the specific signs and symptoms of MELAS. They continue to investigate the effects of mitochondrial gene mutations in different tissues, particularly in the brain. Inheritance
This condition is inherited in a mitochondrial pattern, which is also known as maternal inheritance and heteroplasmy. This pattern of inheritance applies to genes contained in mitochondrial DNA.
Because having a sibling with schizencephaly has been statistically shown to increase risk of the disorder, it is possible that there is a heritable genetic component to the disease. References
9.^ Herrera Ortiz, A., & Ortiz Sandoval, H. (2021). Open Lip Schizencephaly: A Case Report. Revista Cuarzo, 26(2), 27-29.        https://doi.org/10.26752/cuarzo.v26.n2.510

External links
Schizencephaly at NINDS
OMIM entries on Familial Schizencephaly, SIX3-Related