Aarskog-Scott syndrome: a clinical study based on a large series of 111 male patients with a pathogenic variant in FGD1 and management recommendations
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background Aarskog-Scott syndrome (AAS) is a rare condition with multiple congenital anomalies, caused by hemizygote variants in the FGD1 gene. Its description was based mostly on old case reports, in whom a molecular diagnosis was not always available, or on small series. The aim of this study was to better delineate the phenotype and the natural history of AAS and to provide clues for the diagnosis and the management of the patients. Methods Phenotypic characterisation of the largest reported AAS cohort, comprising 111 male patients with proven causative variants in FGD1 , through comprehensive analyses of clinical data including congenital anomalies, growth and neurodevelopment. Review of photographs and radiographs by experts in dysmorphology and skeletal disorders. Results This study refines the phenotypic spectrum of AAS, with the description of new morphological and radiological features, and refines the prevalence of the features. Short stature is less frequent than previously reported and has a prenatal onset in more than half of the patients. The growth has a specific course with a catch-up during the first decade often leading to low-normal stature in adulthood. Whereas intellectual disability is rare, patients with AAS have a high prevalence of specific learning difficulties and attention hyperactivity disorder. In light of this better knowledge of AAS, we provide management recommendations. Conclusion A better knowledge of the natural history and phenotypic spectrum of AAS will be helpful for the clinical diagnosis and for the interpretation of FGD1 variants using a retrophenotyping strategy, which is becoming the most common way of diagnosis nowadays. Recommendations for care will improve the management of the patients.
Source: Journal of Medical Genetics
Authors: Médéric Jeanne, Nathalie Ronce, Solène Remizé, Stéphanie Arpin, Geneviève Baujat, Sylvain Breton, Florence Petit, Clémence Vanlerberghe, Anne Coeslier-Dieux, Sylvie Manouvrier-Hanu, Catherine Vincent-Delorme, Philippe Khau Van Kien, Julien Van-Gils, Chloé Quélin, Laurent Pasquier, Sylvie Odent, Florence Demurger, Fanny Laffargue, Christine Francannet, Dominique Martin-Coignard, Alexandra Afenjar, Sandra Whalen, Alain Verloes, Yline Capri, Andrée Delahaye, Julie Plaisancié, Philippe Labrune, Anne Destree, Isabelle Maystadt, Viorca Ciorna Monferrato, Bertrand Isidor, Marie Vincent, Nolwen Jean Marçais, Sophie Nambot, Elise Schaefer, Salima El Chehadeh, James Lespinasse, Patrick Collignon, Tiffany Busa, Nicole Philip, Marjolaine Willems, Marc Planes, Olivier M Vanakker, Laetitia Lambert, Bruno Leheup, Michèle Mathieu-Dramard, Gilles Morin, Klaus Dieterich, Emmanuelle Ginglinger, Allan Bayat, Meena Balasubramanian, Benjamin Dauriat, Damien Haye, Jeanne Amiel, Marlène Rio, Valérie Cormier-Daire, Annick Toutain
Institutions: Université de Tours, Inserm, Imaging, Brain, and Neuropsychiatry, Centre Hospitalier Universitaire de Tours, Hôpital Necker-Enfants Malades, Université Paris Cité, Institut Necker Enfants Malades, Institut des Maladies Génétiques Imagine, Centre Hospitalier Universitaire de Lille, Centre Hospitalier Universitaire de Nîmes, Centre Hospitalier Universitaire de Bordeaux, Centre Hospitalier Universitaire de Rennes, Centre hospitalier Bretagne Atlantique, Centre Hospitalier Universitaire de Clermont-Ferrand, Centre Hospitalier du Mans, Hôpital Armand-Trousseau, Assistance Publique – Hôpitaux de Paris, Hôpital Robert-Debré, Hôpital Jean-Verdier, Centre Hospitalier Universitaire de Toulouse, Hôpital Antoine-Béclère, Institute of Pathology and Genetics, Centre Hospitalier Régional de Metz-Thionville, Centre Hospitalier Universitaire de Nantes, CHU Dijon Bourgogne, Hôpitaux Universitaires de Strasbourg, Centre Hospitalier Métropole Savoie, Centre Hospitalier Intercommunal Toulon-La Seyne-sur-Mer, Assistance Publique Hôpitaux de Marseille, Hôpital Arnaud de Villeneuve, Centre Hospitalier Régional Universitaire de Brest, Ghent University Hospital, Centre Hospitalier Régional et Universitaire de Nancy, Centre Hospitalier Universitaire Amiens-Picardie, Centre Hospitalier Universitaire de Grenoble, Groupe Hospitalier de la Région de Mulhouse et Sud Alsace, University of Southern Denmark, Sheffield Children's NHS Foundation Trust, Centre Hospitalier Universitaire de Limoges, Hospices Civils de Lyon
Language: English
Topic: Genomics and Rare Diseases
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funder: Medical Research Council
OpenAlex ID: W4406282807