Clinical Guidance
SALL4-related disorders include Duane-radial ray syndrome (DRRS, Okihiro syndrome), acro-renal-ocular syndrome (AROS), and SALL4-related Holt-Oram syndrome (HOS) – three phenotypes previously thought to be distinct entities [, , , , , , ]. • DRRS is characterized by uni- or bilateral Duane anomaly and radial ray malformation that can include thenar hypoplasia and/or hypoplasia or aplasia of the thumbs, hypoplasia or aplasia of the radii, shortening and radial deviation of the forearms, triphalangeal thumbs, and duplication of the thumb (preaxial polydactyly). • AROS is characterized by radial ray malformations, renal abnormalities (mild malrotation, ectopia, horseshoe kidney, renal hypoplasia, vesicoureteral reflux, bladder diverticula), ocular coloboma, and Duane anomaly. • Rarely, pathogenic variants in SALL4 may cause clinically typical HOS (i.e., radial ray malformations and cardiac malformations without additional features). Of 69 affected individuals from 23 families with a SALL4 pathogenic variant, 13% show the triad of Duane anomaly, radial ray malformation, and sensorineural hearing loss originally described for Okihiro syndrome; 45% have Duane anomaly and radial defects; and 21% have radial defects only. To date, more than 100 individuals with a pathogenic variant in SALL4 have been identified [, , , , , , , , , and others]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. SALL4-Related Disorders: Frequency of Select Features
