Clinical and Genetic Characterization of Upper Extremity Anomalies in Robinow Syndrome

Abstract

PURPOSE: Robinow syndrome (RS) is an extremely rare dwarfing syndrome manifesting as craniofacial, genital, and extremity anomalies.1 However, due to the low prevalence and phenotypic heterogeneity of this syndrome, a detailed description of associated upper extremity anomalies does not currently exist.2–5 This study seeks to characterize upper extremity anomalies in the context of known genetic defects to assist in timely and accurate diagnosis of RS. METHODS: Patients with clinically identified RS were invited to our institution for multidisciplinary evaluation. A total of 18 patients were evaluated by plastic surgery, urology, orthopedic surgery, neuropsychology, and genetics teams. Twelve patients ultimately agreed to genetic testing and were found to have a genetic variant of RS. Limb anomalies were surveyed and documented by 3 members of the plastic surgery team with particular attention to the upper extremity. Upper extremity findings were compared to individual genetic variants to elucidate any correlations. RESULTS: A total of 5 genetic variants were identified. Mesomelia (47%) was the most common skeletal dysplasia. Rhizomelia (33%) was limited to patient with variants of the DVL1 and NXN genes. Eight distinct hand anomalies were identified, the most being brachydactyly (92%), broad thumbs (83%), and clinodactyly (75%). Brachydactyly and broad thumbs in particular were evident across all genetic variants. The most common functional deficit was decreased forearm rotation (57%), which was seen in all genetic variants aside from an X-linked GPC4 variant. One patient with a mutation of the NXN gene demonstrated skeletal dysplasia without hand anomalies. CONCLUSION: A trained hand surgeon should be aware of the common findings associated with Robinow syndrome. This is the first study to correlate the genotypic and phenotypic presentation of patients with a confirmed diagnosis of RS. A thorough understanding of the breadth of RS-associated hand anomalies can aid in early identification and proactive management of sequelae. REFERENCES: 1. Robinow M, Silverman FN, Smith HD. A newly recognized dwarfing syndrome. Am J Dis Child. 1969;117:645–651. 2. Bain MD, Winter RM, Burn J. Robinow syndrome without mesomelic brachymelia: a report of five cases. J Med Genet. 1986;23:350–354. 3. Mazzeu JF, Pardono E, Vianna-Morgante AM, et al. Clinical characterization of autosomal dominant and recessive variants of Robinow syndrome. Am J Med Genet A. 2007;143:320–325. 4. Bunn KJ, Lai A, Al-Ani A, et al. An osteosclerotic form of Robinow syndrome. Am J Med Genet A. 2014;164A:2638–2642. 5. Patton MA, Afzal AR. Robinow syndrome. J Med Genet. 2002;39:305–310.