Homozygous deletion of exons 2-7 within TGFB3 gene in a child with severe Loeys-Dietz syndrome and Marfan-like features.

We describe a patient with palatal abnormalities-cleft palate and bifid uvula; distinctive facial features-long and triangular face, large ears and nose, thin lips and dental crowding; musculoskeletal abnormalities-severe scoliosis, joint laxity, long digits, flat feet, decreased muscle mass, and diminished muscle strength; and cardiac features-a dilatated ascending aorta at the level of Valsalva sinuses and a patent foramen ovale. Sequence analysis and deletion/duplication testing for a panel of genes involved in connective tissue disorders revealed the presence of a novel homozygous deletion of exons 2-7 in TGFB3 gene. Heterozygous pathogenic mutations in TGFB3 have been associated with Loeys-Dietz syndrome 5 (LDS5) and Arrhythmogenic Right Ventricular Dysplasia type 1. Here, we report the first case of a homozygous TGFB3 variant associated with a severe LDS5 and Marfan-like presentation.

A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.

BACKGROUND: Clinical and molecular data on the occurrence and frequency of inherited neuromuscular disorders (NMD) in the Lebanese population is scarce. OBJECTIVE: This study aims to provide a retrospective overview of hereditary NMDs based on our clinical consultations in Lebanon. METHODS: Clinical and molecular data of patients referred to a multi-disciplinary consultation for neuromuscular disorders over a 20-year period (1999-2019) was reviewed. RESULTS: A total of 506 patients were diagnosed with 62 different disorders encompassing 10 classes of NMDs. 103 variants in 49 genes were identified. In this cohort, 81.4% of patients were diagnosed with motor neuron diseases and muscular dystrophies, with almost half of these described with spinal muscular atrophy (SMA) (40.3% of patients). We estimate a high SMA incidence of 1 in 7,500 births in Lebanon. Duchenne and Becker muscular dystrophy were the second most frequently diagnosed NMDs (17% of patients). These disorders were associated with the highest number of variants (39) identified in this study. A highly heterogeneous presentation of Limb Girdle Muscular Dystrophy and Charcot-Marie-Tooth disease was notably identified. The least common disorders (5.5% of patients) involved congenital, metabolic, and mitochondrial myopathies, congenital myasthenic syndromes, and myotonic dystrophies. A review of the literature for selected NMDs in Lebanon is provided. CONCLUSIONS: Our study indicates a high prevalence and underreporting of heterogeneous forms of NMDs in Lebanon- a major challenge with many novel NMD treatments in the pipeline. This report calls for a regional NMD patient registry.