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 etiology are hardly available due to the heterogeneity across classification systems. In this study, we aim at defining the CULA etiology of patients that have been evaluated at the Modena University Hospital's Congenital Hand Malformations multidisciplinary clinic in the years 2004 to 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 etiology, including prenatal exposure, somatic mutations and amniotic bands; and (2) Mendelian etiology, 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 etiology 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 etiologies showed a significantly higher frequency of central defects (p = 0.0031). CONCLUSION: The two etiologies differ in terms of patient's clinical features, morphology defect and axis involvement. This data may be helpful to the clinician during the patient's diagnostic workup by indicating the necessity for genetic testing and for determining the anomaly's recurrence risk.

The impact of clinical factors, riluzole and therapeutic interventions on ALS survival: a population based study in Modena, Italy.

The prognostic role of riluzole, enteral nutrition (EN), non-invasive ventilation (NIV) and interdisciplinary care in ALS is still debated. A population based study has been performed focusing on ALS survival, with particular attention to prognostic factors and therapeutic intervention. All patients diagnosed with ALS between 2000 and 2009 and residing in Modena, Italy, have been registered. A centre for motor neuron disease (MND) has been active in our province since 2000, in addition to a prospective registry collecting all incident cases. One hundred and ninety-three incident cases have been collected during the 10 years of the study. Results demonstrated that median survival was 41 months (the overall three-year and five-year survival rates being 54.36% and 28.81%, respectively). Based on univariate analysis, factors related to survival were: age at diagnosis, gender, site of onset, phenotype, riluzole treatment and tracheostomy. In the Cox multivariable model, the factors independently related to a longer survival were age (p < 0.01), site of onset (p = 0.02) and riluzole treatment (p < 0.01), with a median gain in survival of 29 months (patients aged < 55 years compared with patients ≥ 55 years), 20 months (spinal versus bulbar onset), and 12 months (riluzole, yes vs. no), respectively. In conclusion, the study has confirmed the prognostic role of clinical features, but has surprisingly demonstrated that riluzole prolonged life significantly longer than NIV and EN. This observational study described the effects of ALS management in a setting that may approximate routine clinical practice more closely than randomized controlled trial (RCT); effects of uncontrolled potential confounders, however, cannot be excluded.