Milder presentation of autosomal dominant fatty acyl CoA reductase 1‐related syndrome: Report of the first Middle Eastern patient and review of the literature

Abstract The FAR1‐related phenotypes caused by the FAR1 gene encodes the peroxisomal protein fatty acyl‐CoA reductase 1 (FAR1), which is required to reduce fatty acids to fatty alcohols used to form ether‐linked alkyl bonds. Biallelic loss‐of‐function variants have been associated with severe psychomotor developmental delay, seizures, cataracts, growth retardation with microcephaly, and spasticity. However, heterozygous variants in FAR1 have been recently linked to a rare genetic disorder called cataracts, spastic paraparesis, and speech delay (CSPSD). Here, we present the first Middle Eastern patient with a de novo pathogenic heterozygous variant in FAR1 identified by exome sequencing (ES) analysis and a detailed overview of the reported clinical phenotypes and genotypes. Our patient represents the milder end of the clinical spectrum, with medication‐free seizures by the first year of life, proper speech and fine motor development, as well as an absence of other previously reported features such as learning difficulties, axial hypotonia, and joint contracture. In addition, she had developmental dysplasia of the hip (DDH) that failed medical management, as well as faltering growth. Our patient adds to the small number of patients recognized to date and expands the clinical spectrum to provide better clinical delineation, improve diagnosis, and develop precision medicine approaches for this disorder