Rare eye disorder from genetic sources can also be responsible for other effects in the brain and fetal cardiovascular development.
Researchers at Children's Hospital Boston, who specialize in studying the genetics of rare eye-movement disorders, have found a rare genetic syndrome whose implications go far beyond the eye, raising intriguing questions about human cardiovascular and brain development.
The syndrome involves a mutation to HOXA1, a gene that has been extensively studied in mice, but about which little is known in humans. HOXA1 belongs to a large family of HOX genes that govern very early embryonic development and the making of the body plan. HOXA1 is the first HOX gene turned on in mice, and presumably in the human body, and is involved in patterning of the growth of the head, face, and brainstem.
Mice that lack both copies of HOXA1 universally die. Until this study, no human HOXA1 mutation had ever been identified, and it was assumed that complete loss of HOXA1 function would be lethal. But the Children's investigators, have found living people with two mutated copies of HOXA1 -- from three different parts of the world.
Researchers had been studying genetic disorders that interfere with peoples' ability to move their eyes horizontally (left or right). Collaborators in Saudi Arabia alerted them to patients they'd been seeing who had not only restricted horizontal eye movement, but also deafness and motor impairments. The Saudi clinicians began to carefully reexamine their patients, while US researchers looked at the patients' DNA to try to identify a causative gene.
All 9 patients with the syndrome (dubbed Bosley-Salih-Alorainy syndrome, or BSAS, after the Saudi discoverers) had horizontal gaze abnormalities. Eight were profoundly deaf, 3 had external ear defects, 7 had delayed motor development, and 2 met criteria for autism spectrum disorder with cognitive and behavioral impairment. In addition, 7 had malformations or complete absence of one or both internal carotid arteries, one of the two carotid arteries that are the main suppliers of blood to the brain.