Genetic basis of congenital upper limb anomalies: analysis of 487 cases of a specialized clinic

Background: Specific data regarding the frequencies of the congenital upper limb anomalies (CULA) according to their aetiology are hardly available due to the heterogeneity across classification systems. In this study, we aim at defining the aetiology of CULA of the patients attending Modena University Hospital’s Congenital Hand Malformations multidisciplinary clinic in the years 2004-2012. Methods: Medical records of 487 patients were retrospectively reviewed. On the basis of clinical, anamnestic and genetic data the CULA were distributed into two main groups: (1) non-mendelian aetiology, including prenatal exposure, somatic mutations and amniotic bands and (2) mendelian aetiology including single gene and genomic/chromosomal diseases. CULA were further grouped according to the embryological damage (formation, separation and growth defects) and to the involved axis (radial, ulnar, central). Results: A mendelian aetiology was diagnosed in 199 patients (40.9%), whereas the remaining 288 cases (59.1%) were described as non-mendelian. The involvement of the lower limbs, the presence of malformations in other organs and facial dysmorphisms were significantly more represented in the mendelian cases. The formation defects were significantly more frequent in the non-mendelian group (p<0.001), whereas the frequency of separation defects was higher in the mendelian cases (p=0.0025). Patients with non-mendelian aetiologies showed a significantly higher frequency of central defects (p=0.0031). Conclusion: The two aetiologies differ in terms of patient’s clinical features, morphology defect and axis involvement. These data may be helpful in the diagnostic workup for the indication to perform genetic testing and for the recurrence risk assessment.