A Rare Case Diagnosed with Developmental and Epileptic Encephalopathy 49

Developmental and Epileptic Encephalopathy 49 (DEE49) (OMIM # 617281) is a severe autosomal recessive neurologic disorder. The clinical findings of DEE49 consist of the onset of seizures in the neonatal period, microcephaly, hypotonia, global developmental delay with intellectual disability and lack of speech, spasticity, and coarse facial features. Most patients of DEE49 have brain calcifications on brain imaging. DEE49 is caused by a homozygous or compound heterozygous mutation in the DENND5A gene (OMIM * 617278) on chromosome 11p151 (1). In this case study, the Whole Exome Sequencing of the patient found a likely pathogenic homozygous de novo SNV within the DENND5A gene [NM_015213.4: chr11-9171678 CT>C; c.2684del; p.Lys895SerfsTer7]. There are very few patients with DEE49 reported in the literature. As far as we know, the variant we identified is reported for the first time with DEE49 clinic. We predicted that the clinical findings and the variant detected in our patient will contribute to phenotype-genotype correlation. In addition, DENND5A gene mutation and DEE49 should be considered in the differential diagnosis in patients with brain calcifications.

Reference 1. Han C, Alkhater R, Froukh T, Minassian AG, Galati M, Liu RH, Fotouhi M, Sommerfeld J, Alfrook AJ, Marshall C, Walker S, Bauer P, Scherer SW, Riess O, Buchert R, Minassian BA, McPherson PS. Epileptic Encephalopathy Caused by Mutations in the Guanine Nucleotide Exchange Factor DENND5A. Am J Hum Genet. 2016 Dec 1;99(6):1359-1367. doi: 10.1016/j.ajhg.2016.10.006. Epub 2016 Nov 17. PMID: 27866705; PMCID: PMC5142110.

Mehmet Burak Mutlu
DETAGEN Genetic Diseases Evaluation Center
Turkey

Hakan Gümüş
Erciyes University Medical Faculty
Turkey

Ümmü Gülsüm Özgül Gümüş
Health Ministry of Turkish Republic Kayseri City Hospital
Turkey