Duane-radial ray syndrome (DRRS), also known as Okihiro syndrome, is a rare congenital developmental disorder characterized by the association of Duane retraction syndrome (DRS) with preaxial upper limb malformations, particularly radial ray defects. First described by Okihiro and colleagues in 1977, this condition represents a syndromic form of congenital cranial dysinnervation disorder (CCDD) in which aberrant ocular motor innervation coexists with limb morphogenesis anomalies. The syndrome follows an autosomal dominant inheritance pattern with marked variable expressivity and incomplete penetrance, meaning affected individuals within the same family may display widely differing phenotypes ranging from mild ocular findings to significant limb and systemic involvement. From a developmental perspective, DRRS is categorized among congenital cranial dysinnervation disorders, a group of conditions characterized by primary developmental anomalies of cranial nerve nuclei or their axonal projections rather than primary muscle pathology. This classification underscores the neurodevelopmental origin of the ocular motility disturbance. Recognition of DRRS is clinically important because ocular findings may serve as the first diagnostic clue to an underlying multisystem developmental disorder. At the molecular level, Duane-radial ray syndrome is primarily associated with pathogenic variants in the spalt-like transcription factor 4 (SALL4) gene located on chromosome 20q13.2. SALL4 encodes a zinc finger transcription factor that plays a critical role in embryogenesis, particularly in limb bud formation, ocular development, cardiac morphogenesis, renal differentiation, and neural patterning. Haploinsufficiency of SALL4 disrupts transcriptional regulation during early organogenesis, leading to the constellation of malformations observed in this syndrome. DRRS belongs to the broader spectrum of SALL4-related disorders, which may show phenotypic overlap with conditions such as Holt–Oram syndrome, acro-renal-ocular syndrome, and even thalidomide embryopathy. Because of these overlaps, molecular confirmation through genetic testing is often essential for accurate diagnosis, appropriate counseling, and differentiation from other radial ray syndromes. The hallmark ocular feature of DRRS is Duane retraction syndrome, a congenital strabismus disorder characterized by limited horizontal eye movement due to aberrant innervation of the lateral rectus muscle. In classic DRS, the abducens nerve (cranial nerve VI) is congenitally absent or hypoplastic, with anomalous innervation of the lateral rectus muscle by branches of the oculomotor nerve (cranial nerve III). This miswiring leads to paradoxical co-contraction of the medial and lateral rectus muscles during attempted adduction, resulting in globe retraction and narrowing of the palpebral fissure. Abduction limitation is most common, although adduction limitation or combined forms may also occur. Vertical upshoots or downshoots during adduction can be observed due to mechanical leash effects or anomalous muscle contraction. In DRRS, the DRS is typically unilateral but may be bilateral. Patients often present in infancy or early childhood with strabismus, compensatory head posture, or reduced binocular vision. Amblyopia may develop if fixation preference or significant anisometropia is present. In addition to the classic features of DRS, other ocular anomalies have occasionally been reported in association with DRRS. These findings may include ptosis, epibulbar dermoids, microphthalmia, coloboma, optic disc anomalies, and refractive errors. However, Duane retraction syndrome remains the most consistent and defining ophthalmic manifestation. The second defining feature of Duane-radial ray syndrome is the presence of radial ray malformations of the upper limbs. These anomalies involve the preaxial structures of the forearm and hand and may vary widely in severity. Common manifestations include hypoplastic or absent thumbs, triphalangeal thumbs, radial hypoplasia, shortened forearms, and radioulnar synostosis. The anomalies are often asymmetric and may be unilateral or bilateral. In some individuals, the limb defects may be subtle, such as mild thumb hypoplasia, while the phenotype may be more severe in others, with complete absence of the radius. These skeletal anomalies arise from disrupted mesodermal differentiation and impaired patterning during early limb bud development. The wide variability in limb involvement reflects the variable expressivity of SALL4 mutations. Beyond ocular and limb anomalies, DRRS may involve other organ systems, reflecting SALL4's pleiotropic role in embryogenesis. Renal anomalies are among the most frequently reported systemic associations and may include unilateral renal agenesis, ectopic kidney, horseshoe kidney, vesicoureteral reflux, or structural anomalies detectable on imaging. Cardiac defects have also been documented, including atrial septal defects, ventricular septal defects, and conduction abnormalities. Hearing impairment, particularly sensorineural hearing loss, has been reported in some individuals. Less commonly, gastrointestinal, vertebral, or facial anomalies may be present. Because systemic involvement may not be clinically apparent at birth, a comprehensive evaluation is recommended once DRRS is suspected. The differential diagnosis of Duane-radial ray syndrome includes other radial ray syndromes and conditions associated with congenital strabismus. For example, Holt–Oram syndrome, also caused by mutations in the SALL4 gene, presents with radial ray defects and cardiac anomalies but does not typically include Duane retraction syndrome. Thalidomide embryopathy may mimic DRRS with limb reduction defects and ocular anomalies; however, the etiology is teratogenic rather than genetic. Isolated Duane retraction syndrome lacks associated limb anomalies. Therefore, the coexistence of DRS with radial ray anomalies should prompt consideration of DRRS and genetic testing for SALL4 mutations. Diagnosis of DRRS is initially clinical, based on recognition of the characteristic ocular motility pattern of Duane retraction syndrome in conjunction with radial ray malformations. A detailed family history may reveal autosomal dominant inheritance across generations. Genetic testing confirming a pathogenic SALL4 variant establishes the diagnosis and facilitates genetic counseling. Prenatal diagnosis may be considered in families with known mutations through targeted molecular testing. Management of Duane-radial ray syndrome requires a multidisciplinary approach. Ophthalmologic care focuses on amblyopia prevention, refractive correction, monitoring of binocular vision, and surgical intervention when indicated for significant head posture or cosmetically unacceptable deviation. Orthopedic management addresses limb anomalies and functional limitations. Renal ultrasonography and cardiac evaluation are recommended to screen for associated anomalies. Audiological assessment may be warranted. Genetic counseling plays a crucial role in informing affected individuals and families about inheritance patterns, recurrence risks, and reproductive options. In summary, Duane-radial ray syndrome is a rare but clinically significant developmental disorder characterized by the association of Duane retraction syndrome and radial ray malformations, most commonly caused by mutations in the SALL4 gene. It exemplifies the intersection of neurodevelopmental ocular dysinnervation and limb morphogenesis defects within a broader multisystem embryologic framework. Early recognition, particularly by ophthalmologists encountering Duane retraction syndrome in a child with limb anomalies, is essential for comprehensive systemic evaluation, coordinated multidisciplinary care, and appropriate genetic counseling.