Retrospective evaluation of the importance of NGS multigene panel in the diagnosis process in patients with marfanoid habitus

Aim: Marfanoid habitus is characteristically observed in Marfan syndrome. However, there are also syndromes with varying degrees (completely or partially). Multiple syndromes such as Loeys-Dietz syndrome, Homocystinuria, Ehlers-Danlos syndrome classical type, classical-like type, arthrochalasia type, vascular type, kyphoscoliotic type, spondylodisplastic type, periodontal type, COL1A1 and CO1A2 gene related syndromes, some Kutis laxa syndrome subtypes, Stickler syndrome, Weill-Marchesani syndrome, Arterial tortuosity syndrome, Congenital contractural arachnodactyly (Beals syndrome), Lujan-Fryns syndrome, CamuratiEngelmann disease, Multiple Endocrine Neoplasia type 2b (MEN 2B), Cold induced sweating syndrome, Shprintzen-Goldberg syndrome, X-linked mental retardation syndromes, Familial thoracic aortic aneurysm syndromes also display marfanoid features phenotypically to varying degrees. They are included in the differential diagnosis with Marfan syndrome. The results and success rate of the NGS multigene panel, which we designed from OMIM database-related syndromes sharing a Marfanoid habitus with known genotypes, in our 62 case series were evaluated retrospectively and compared with similar studies. Materials and Methods: Marfanoid habitus NGS multigene panel results, laboratory results, demographic data and photographs of our 62 case series, who were referred to the Medical Genetics outpatient clinic between 2016-2022 due to marfanoid appearance, were retrospectively analyzed. Results: In the results of the YND gene panel, variants were detected in 28 of our 51 cases, 4 of which were in the FBN1 gene, a clinically definite diagnosis in 16 cases, a clinical diagnosis with a high probability in 2 cases, and a clinical suspicion in 10 cases. The success rate of the panel was found to be approximately 54.9% when evaluated in terms of clinically certain, high probability and suspicious variants. The panel success rate is 31.3% when evaluated specifically for cases with a definite diagnosis according to the results of clinical evaluation and molecular analysis. In the whole exome sequence analysis (TED) analysis, 7 different variants were detected in only 6 different genes. Conclusions: As we mentioned in our study in cases with marfanoid habitus, the diagnosis process can sometimes be prolonged and the diagnosis of the cases may be incomplete. In terms x of the related syndrome group, it is very important to clarify the genotypic change in issues such as reducing the morbidity and mortality of the cases, revealing the etiology, obtaining appropriate genetic counseling, eliminating the anxiety caused by the wrong prediagnosis on the families, evaluating the family members at risk, and evaluating the risk of recurrence for the next generations. When evaluated together with the success rate in our study, our marfanoid habitus NGS gene panel seems quite successful and NGS analysis has a very important place in the diagnosis in similar syndrome groups. It was aimed to present a diagnostic test that can save time and cost in cases with the related phenotype, where cardiovascular and ocular system findings may be severe. Keywords: marfanoid habitus, NGS, multigene panel