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To date, 125 patients from 38 families have been reported.

Okihiro syndrome has been originally characterized by the association of radial defects, Duane anomaly and deafness. Uni- or bilateral radial defects are observed in more than 90% of the patients and range from isolated thenar hypoplasia and/or hypoplasia or aplasia of the thumbs (40%) to hypoplasia or aplasia of the radii (30%), with sometimes ulnar or humeral hypoplasia (10%). Triphalangeal thumbs and pre-axial polydactyly have also been reported (20%). Duane anomaly is observed in 50% of the patients (bilateral in 20%). Renal abnormalities may include kidney ectopia, and rarely renal hypoplasia or horseshoe kidney. Sensorineural or conductive deafness is observed in 30% of the patients, sometimes associated with ear dysplasia. Heart defects (10%), such as ventricular or atrial septal defects, tetralogy of Fallot, or conduction disturbances (5%) have also been reported. Scoliosis is observed in 10% of patients. Gastrointestinal manifestations (anal stenosis, imperforate anus, choanal atresia) could be associated.

Okihiro syndrome is caused by heterozygous variants in SALL4 gene (20q13.2). The phenotypes caused by SALL4 deletions are not different from those caused by point mutations.

Okihiro syndrome is suspected on clinical findings and sometimes on family history. Careful clinical examination (sometimes upper limb defects can be mild, such as thenar hypoplasia), a complete eye examination by an ophthalmologist with special attention to extraocular movements, and hearing tests are required. Abdominal and cardiac ultrasound, spinal X-rays and complete blood cell count should be performed to look for associated features, sometimes suggesting a differential diagnosis. The clinical suspicion can be confirmed by SALL4 molecular analysis.

The phenotype overlaps with Holt-Oram syndrome, Townes-Brocks syndrome Fanconi anemia, VACTERL/VATER association, isolated Duane retraction and fetal valproate syndrome.

Some features can be diagnosed during pregnancy, such as severe limb involvement, heart defects or renal abnormalities. Genetic prenatal diagnosis is possible if the pathogenic variant has previously been identified in a family member.

Okihiro syndrome is an autosomal dominant genetic condition. Genetic counseling should be provided to affected individuals and their families informing them that, for each pregnancy, there is a 50% risk of disease transmission from an individual with a pathogenic variant to their offspring. The phenotype is highly variable and mostly fully penetrant. SALL4 variants may occur de novo. Parental segregation analysis should be performed, even in absence of symptoms, to determine genetic counselling.

Management is multidisciplinary and includes, at diagnosis, ophthalmological, cardiac, renal, hearing and genetic evaluations. Treatment depends on manifestations: limb, eye and/or heart surgery, occupational therapy, limb prothesis, orthoptic reeducation, physiotherapy, hearing aids, pacemaker. Surveillance depends on manifestations. Electrocardiogram is recommended regularly for adults. The social and psychological impact of the condition should be assessed and assisted. Women with Okihiro syndrome and cardiac defects should be evaluated by a cardiologist to determine what monitoring and care may be needed during pregnancy.

Prognosis is highly variable, according to the severity of the clinical manifestations, and their functional, social and psychological impacts in everyday life. Life expectancy depends on the severity of heart defects and renal function.