Spina bifida (SB) is the most common congenital malformation of the central nervous system (CNS), which develops as a result of disrupted primary neurulation and neural tube closure. Myelomeningocele (MMC) is the most severe SB form and belongs to a larger group of congenital malformations known as neural tube defects (NTDs). MMC occurs when a portion of the spinal cord or nerves protrudes from an opening in the spine and may or may not be covered by meninges. MMC can be associated with hydrocephalus (HC), Arnold-Chiari II malformation, bowel and bladder dysfunction, lower limb paralysis, and pain syndromes. Despite many studies suggesting possible MMC causes such as folic acid deficiency, genetic disorders, ethnicity, and maternal health characteristics, the mechanism of MMC, particularly its concurrence with HC, is still unclear. To address such shortcomings, the whole exome sequencing (WES) of cadaveric DNA procured from the body of a 55-year-old female with concurrent MMC and HC was performed on the Illumina next-generation sequencing (NGS) platform. The bioinformatics analysis of WES data yielded 84 rare (minor allele frequency, MAF ≤ 0.01) pathologic/deleterious genetic variants, with few of the affected genes being previously linked to NTD/MMC or HC. The most interesting such genes were ALDH1L1 and DNAAF1 because they have been previously reported to be associated with both NTD/MMC and HC. The great extent of HC association with MMC raises a question of whether the ALDH1L1 and DNAFF1 mutations could, at least in some cases, underline the concurrent MMC and HC in humans.
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