Okihiro syndrome due to a point mutation

Okihiro syndrome due to a point mutation, also known as Duane-radial ray syndrome (DRRS) caused by a point mutation in the SALL4 gene, is a rare congenital disorder that affects multiple body systems. This specific subtype is distinguished from Okihiro syndrome caused by larger deletions or other mutation types in the SALL4 gene on chromosome 20q13.2. The condition is characterized by the combination of Duane anomaly (a type of eye movement disorder in which the ability to move one or both eyes outward is limited, often with retraction of the eyeball on attempted inward gaze) and radial ray malformations affecting the upper limbs. Upper limb abnormalities can range from mild thumb hypoplasia or triphalangeal thumbs to complete absence of the thumb or radius, and may also include thenar muscle weakness or forearm anomalies. Beyond the hallmark features, Okihiro syndrome can affect additional organ systems. Some patients may have sensorineural or conductive hearing loss, renal malformations (such as horseshoe kidney, renal ectopia, or vesicoureteral reflux), and congenital heart defects (including atrial or ventricular septal defects and tetralogy of Fallot). Anal anomalies, including anal stenosis or imperforate anus, have also been reported. The clinical presentation is highly variable, even within the same family, meaning that some affected individuals may have only subtle findings while others have more significant multi-organ involvement. There is currently no cure for Okihiro syndrome. Management is supportive and multidisciplinary, tailored to the specific features present in each patient. This may include surgical correction of limb anomalies (such as pollicization for absent thumbs), strabismus surgery for Duane anomaly, hearing aids or cochlear implants for hearing loss, cardiac surgery for significant heart defects, and urological or surgical management for renal or anal malformations. Regular monitoring by a team including ophthalmologists, orthopedic surgeons, cardiologists, audiologists, and nephrologists is recommended. Genetic counseling is important for affected families given the autosomal dominant inheritance pattern.

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