Germline alterations of the ubiquitin-conjugating enzyme E2 A (UBE2A) gene coding for the ubiquitin-conjugating enzyme 2A [40] are associated with X-linked syndromic mental retardation, a disease characterized by abnormal intellectual development and dysmorphic features, such as large head, wide mouth, almond-shaped eyes, and onychodystrophy. This evidence concerns the gene UBE2A and X-linked syndromic intellectual disability.