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Multiorgan manifestations of COL4A1 and COL4A2 variants and proposal for a clinical management protocol.
Gasparini, Simone; Balestrini, Simona; Saccaro, Luigi Francesco; Bacci, Giacomo; Panichella, Giorgia; Montomoli, Martino; Cantalupo, Gaetano; Bigoni, Stefania; Mancano, Giorgia; Pellacani, Simona; Leuzzi, Vincenzo; Volpi, Nila; Mari, Francesco; Melani, Federico; Cavallin, Mara; Pisano, Tiziana; Porcedda, Giulio; Vaglio, Augusto; Mei, Davide; Barba, Carmen; Parrini, Elena; Guerrini, Renzo.
Afiliación
  • Gasparini S; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCCS (full member of the European Reference Network EpiCARE), Florence, Italy.
  • Balestrini S; University of Florence, Florence, Italy.
  • Saccaro LF; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCCS (full member of the European Reference Network EpiCARE), Florence, Italy.
  • Bacci G; University of Florence, Florence, Italy.
  • Panichella G; Department of Psychiatry, Geneva University and Geneva University Hospitals, Geneva, Switzerland.
  • Montomoli M; Pediatric Ophthalmology Unit, Meyer Children's Hospital IRCCS, Florence, Italy.
  • Cantalupo G; University of Florence, Florence, Italy.
  • Bigoni S; Department of Clinical and Experimental Medicine, University Hospital Careggi, Florence, Italy.
  • Mancano G; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCCS (full member of the European Reference Network EpiCARE), Florence, Italy.
  • Pellacani S; Child Neuropsychiatry Unit, University Hospital of Verona (full member of the European Reference Network EpiCARE), Verona, Italy.
  • Leuzzi V; Department of Engineering for Innovation Medicine, Innovation Biomedicine Section, University of Verona, Verona, Italy.
  • Volpi N; Center for Research on Epilepsy in Pediatric Age (CREP), University Hospital of Verona, Verona, Italy.
  • Mari F; Medical Genetics Unit, Ferrara University Hospital, Ferrara, Italy.
  • Melani F; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCCS (full member of the European Reference Network EpiCARE), Florence, Italy.
  • Cavallin M; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCCS (full member of the European Reference Network EpiCARE), Florence, Italy.
  • Pisano T; University of Florence, Florence, Italy.
  • Porcedda G; Unit of Child Neurology and Psychiatry, Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy.
  • Vaglio A; Neurology and Clinical Neurophysiology Unit, Department of Medical, Surgical and Neurological Sciences, University of Siena, Siena, Italy.
  • Mei D; Child and Adolescent Epilepsy and Clinical Neurophysiology Departmental Unit, USL Centro Toscana, Prato, Italy.
  • Barba C; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCCS (full member of the European Reference Network EpiCARE), Florence, Italy.
  • Parrini E; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCCS (full member of the European Reference Network EpiCARE), Florence, Italy.
  • Guerrini R; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCCS (full member of the European Reference Network EpiCARE), Florence, Italy.
Am J Med Genet C Semin Med Genet ; : e32099, 2024 Jul 17.
Article en En | MEDLINE | ID: mdl-39016117
ABSTRACT
COL4A1/2 variants are associated with highly variable multiorgan manifestations. Depicting the whole clinical spectrum of COL4A1/2-related manifestations is challenging, and there is no consensus on management and preventative strategies. Based on a systematic review of current evidence on COL4A1/2-related disease, we developed a clinical questionnaire that we administered to 43 individuals from 23 distinct families carrying pathogenic variants. In this cohort, we extended ophthalmological and cardiological examinations to asymptomatic individuals and those with only limited or mild, often nonspecific, clinical signs commonly occurring in the general population (i.e., oligosymptomatic). The most frequent clinical findings emerging from both the literature review and the questionnaire included stroke (203/685, 29.6%), seizures or epilepsy (199/685, 29.0%), intellectual disability or developmental delay (168/685, 24.5%), porencephaly/schizencephaly (168/685, 24.5%), motor impairment (162/685, 23.6%), cataract (124/685, 18.1%), hematuria (63/685, 9.2%), and retinal arterial tortuosity (58/685, 8.5%). In oligosymptomatic and asymptomatic carriers, ophthalmological investigations detected retinal vascular tortuosity (5/13, 38.5%), dysgenesis of the anterior segment (4/13, 30.8%), and cataract (2/13, 15.4%), while cardiological investigations were unremarkable except for mild ascending aortic ectasia in 1/8 (12.5%). Our multimodal approach confirms highly variable penetrance and expressivity in COL4A1/2-related conditions, even at the intrafamilial level with neurological involvement being the most frequent and severe finding in both children and adults. We propose a protocol for prevention and management based on individualized risk estimation and periodic multiorgan evaluations.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Med Genet C Semin Med Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Am J Med Genet C Semin Med Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Estados Unidos