MYH9-related disease

May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness

Marco Seri, Alessandro Pecci, Filomena Di Bari, Roberto Cusano, Maria Savino, Emanuele Panza, Alessandra Nigro, Patrizia Noris, Simone Gangarossa, Bianca Rocca, Paolo Gresele, Nicola Bizzaro, Paola Malatesta, Pasi A. Koivisto, Ilaria Longo, Roberto Musso, Carmine Pecoraro, Achille Iolascon, Umberto Magrini, Juan Rodriguez Soriano & 5 others Alessandra Renieri, Gian Marco Ghiggeri, Roberto Ravazzolo, Carlo L. Balduini, Anna Savoia

Research output: Contribution to journalArticle

231 Citations (Scopus)

Abstract

May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families. Since no genotype-phenotype correlation was established, we performed an accurate clinical and biochemical re-evaluation of patients. In addition to macrothrombocytopenia, an abnormal distribution of NMMHC-IIA within leukocytes was observed in all individuals, including those without Döhle-like bodies. Selective, high-tone hearing deficiency and cataract was diagnosed in 83% and 23%, respectively, of patients initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney abnormalities, such as hematuria and proteinuria, affected not only patients referred as Fechtner syndrome and Epstein syndrome but also those referred as May-Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but rather a single disorder with a continuous clinical spectrum varying from mild macrothrombocytopenia with leukocyte inclusions to a severe form complicated by hearing loss, cataracts, and renal failure. For this new nosologic entity, we propose the term "MHY9-related disease," which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects.

Original languageEnglish
Pages (from-to)203-215
Number of pages13
JournalMedicine (United States)
Volume82
Issue number3
DOIs
Publication statusPublished - May 2003

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Cataract
Myosin Heavy Chains
MYH9-Related Disorders
Hearing
Kidney
Mutation
Nephritis
Sensorineural Hearing Loss
Genetic Association Studies
Hematuria
Proteinuria
Hearing Loss
Renal Insufficiency
Leukocytes
Genes

ASJC Scopus subject areas

  • Medicine(all)

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MYH9-related disease : May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. / Seri, Marco; Pecci, Alessandro; Di Bari, Filomena; Cusano, Roberto; Savino, Maria; Panza, Emanuele; Nigro, Alessandra; Noris, Patrizia; Gangarossa, Simone; Rocca, Bianca; Gresele, Paolo; Bizzaro, Nicola; Malatesta, Paola; Koivisto, Pasi A.; Longo, Ilaria; Musso, Roberto; Pecoraro, Carmine; Iolascon, Achille; Magrini, Umberto; Rodriguez Soriano, Juan; Renieri, Alessandra; Ghiggeri, Gian Marco; Ravazzolo, Roberto; Balduini, Carlo L.; Savoia, Anna.

In: Medicine (United States), Vol. 82, No. 3, 05.2003, p. 203-215.

Research output: Contribution to journalArticle

Seri, M, Pecci, A, Di Bari, F, Cusano, R, Savino, M, Panza, E, Nigro, A, Noris, P, Gangarossa, S, Rocca, B, Gresele, P, Bizzaro, N, Malatesta, P, Koivisto, PA, Longo, I, Musso, R, Pecoraro, C, Iolascon, A, Magrini, U, Rodriguez Soriano, J, Renieri, A, Ghiggeri, GM, Ravazzolo, R, Balduini, CL & Savoia, A 2003, 'MYH9-related disease: May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness', Medicine (United States), vol. 82, no. 3, pp. 203-215. https://doi.org/10.1097/00005792-200305000-00006
Seri, Marco ; Pecci, Alessandro ; Di Bari, Filomena ; Cusano, Roberto ; Savino, Maria ; Panza, Emanuele ; Nigro, Alessandra ; Noris, Patrizia ; Gangarossa, Simone ; Rocca, Bianca ; Gresele, Paolo ; Bizzaro, Nicola ; Malatesta, Paola ; Koivisto, Pasi A. ; Longo, Ilaria ; Musso, Roberto ; Pecoraro, Carmine ; Iolascon, Achille ; Magrini, Umberto ; Rodriguez Soriano, Juan ; Renieri, Alessandra ; Ghiggeri, Gian Marco ; Ravazzolo, Roberto ; Balduini, Carlo L. ; Savoia, Anna. / MYH9-related disease : May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness. In: Medicine (United States). 2003 ; Vol. 82, No. 3. pp. 203-215.
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abstract = "May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear D{\"o}hle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families. Since no genotype-phenotype correlation was established, we performed an accurate clinical and biochemical re-evaluation of patients. In addition to macrothrombocytopenia, an abnormal distribution of NMMHC-IIA within leukocytes was observed in all individuals, including those without D{\"o}hle-like bodies. Selective, high-tone hearing deficiency and cataract was diagnosed in 83{\%} and 23{\%}, respectively, of patients initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney abnormalities, such as hematuria and proteinuria, affected not only patients referred as Fechtner syndrome and Epstein syndrome but also those referred as May-Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but rather a single disorder with a continuous clinical spectrum varying from mild macrothrombocytopenia with leukocyte inclusions to a severe form complicated by hearing loss, cataracts, and renal failure. For this new nosologic entity, we propose the term {"}MHY9-related disease,{"} which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects.",
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T2 - May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but represent a variable expression of a single illness

AU - Seri, Marco

AU - Pecci, Alessandro

AU - Di Bari, Filomena

AU - Cusano, Roberto

AU - Savino, Maria

AU - Panza, Emanuele

AU - Nigro, Alessandra

AU - Noris, Patrizia

AU - Gangarossa, Simone

AU - Rocca, Bianca

AU - Gresele, Paolo

AU - Bizzaro, Nicola

AU - Malatesta, Paola

AU - Koivisto, Pasi A.

AU - Longo, Ilaria

AU - Musso, Roberto

AU - Pecoraro, Carmine

AU - Iolascon, Achille

AU - Magrini, Umberto

AU - Rodriguez Soriano, Juan

AU - Renieri, Alessandra

AU - Ghiggeri, Gian Marco

AU - Ravazzolo, Roberto

AU - Balduini, Carlo L.

AU - Savoia, Anna

PY - 2003/5

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N2 - May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are autosomal dominant macrothrombocytopenias distinguished by different combinations of clinical and laboratory signs, such as sensorineural hearing loss, cataract, nephritis, and polymorphonuclear Döhle-like bodies. Mutations in the MYH9 gene encoding for the nonmuscle myosin heavy chain IIA (NMMHC-IIA) have been identified in all these syndromes. To understand the role of the MYH9 mutations, we report the molecular defects in 12 new cases, which together with our previous works represent a cohort of 19 families. Since no genotype-phenotype correlation was established, we performed an accurate clinical and biochemical re-evaluation of patients. In addition to macrothrombocytopenia, an abnormal distribution of NMMHC-IIA within leukocytes was observed in all individuals, including those without Döhle-like bodies. Selective, high-tone hearing deficiency and cataract was diagnosed in 83% and 23%, respectively, of patients initially referred as having May-Hegglin anomaly or Sebastian syndrome. Kidney abnormalities, such as hematuria and proteinuria, affected not only patients referred as Fechtner syndrome and Epstein syndrome but also those referred as May-Hegglin anomaly and Sebastian syndrome. These findings allowed us to conclude that May-Hegglin anomaly, Sebastian syndrome, Fechtner syndrome, and Epstein syndrome are not distinct entities but rather a single disorder with a continuous clinical spectrum varying from mild macrothrombocytopenia with leukocyte inclusions to a severe form complicated by hearing loss, cataracts, and renal failure. For this new nosologic entity, we propose the term "MHY9-related disease," which better interprets the recent knowledge in this field and identifies all patients at risk of developing renal, hearing, or visual defects.

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