Abstract
Abstract
Background
Malan syndrome (MALNS) is a recently described ultrarare syndrome lacking guidelines for diagnosis, management and monitoring of evolutive complications. Less than 90 patients are reported in the literature and limited clinical information are available to assure a proper health surveillance.
Results
A multidisciplinary team with high expertise in MALNS has been launched at the “Ospedale Pediatrico Bambino Gesù”, Rome, Italy. Sixteen Italian MALNS individuals with molecular confirmed clinical diagnosis of MALNS were enrolled in the program. For all patients, 1-year surveillance in a dedicated outpatient Clinic was attained. The expert panel group enrolled 16 patients and performed a deep phenotyping analysis directed to clinically profiling the disorder and performing critical revision of previously reported individuals. Some evolutive complications were also assessed. Previously unappreciated features (e.g., high risk of bone fractures in childhood, neurological/neurovegetative symptoms, noise sensitivity and Chiari malformation type 1) requiring active surveillance were identified. A second case of neoplasm was recorded. No major cardiovascular anomalies were noticed. An accurate clinical description of 9 new MALNS cases was provided.
Conclusions
Deep phenotyping has provided a more accurate characterization of the main clinical features of MALNS and allows broadening the spectrum of disease. A minimal dataset of clinical evaluations and follow-up timeline has been proposed for proper management of patients affected by this ultrarare disorder.
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics (clinical),General Medicine
Reference36 articles.
1. Malan V, Rajan D, Thomas S, et al. Distinct effects of allelic NFIX mutations on nonsense-mediated mRNA decay engender either a Sotos-like or a Marshall–Smith syndrome. Am J Hum Genet. 2010;87(2):189–98.
2. Priolo M, Schanze D, Tatton-Brown K, et al. Further delineation of Malan syndrome. Hum Mutat. 2018;39(9):1226–37.
3. Orphanet-The portal for rare diseases and orphan drugs-Malan Syndrome https://www.orpha.net/consor/cgibin/Disease_Search.php?lng=EN&data_id=23101&Disease_Disease_Search_diseaseGroup=malan&Disease_Disease_Search_diseaseType=Pat&Disease(s)/groupofdiseases=Malan-overgrowth-syndrome&title=Malanovergrowthsyndrome&search=Disease_Search_Simple
4. Bellucco FT, de Mello CB, Meloni VA, Melaragno MI. Malan syndrome in a patient with 19p13.2p13.12 deletion encompassing NFIX and CACNA1A genes: case report and review of the literature. Mol Genet Genomic Med. 2019;7(12):e997.
5. Tabata K, Iida A, Takeshita E, et al. A novel pathogenic NFIX variant in a Malan syndrome patient associated with hindbrain overcrowding. J Neurol Sci. 2020;412:116758.
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