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The Molecular Genetics of Hirschsprung’s Disease

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Hirschsprung's Disease and Allied Disorders

Abstract

Hirschsprung’s disease (HSCR), or aganglionic megacolon, is a classic example of a complex genetic disease, characterized by the lack of enteric ganglia in the submucosal and myenteric plexuses, along variable portions of the distal gut. Since it is caused by a premature arrest of the migration of neural crest cells along the hindgut, it is defined also as a neurocristopathy. The variable extent of aganglionosis correlates with severity of the disease, leading to a classification of HSCR into short- and long-segment phenotypes [1, 2]. S-forms include aganglionosis confined below the rectosigmoid junction (80% of patients), while L-forms (20% of patients) can extend below the splenic flexure (colonic forms, 9%), to the whole colon (total colonic aganglionosis, TCA, 5–10%), or up to the whole bowel (total intestinal). The disease is a congenital malformation occurring in 1 in 5,000 live births, with the highest incidence in Asian populations (2.8 in 10,000), intermediate in Afro-Americans (2.1 in 10,000) and Caucasians (1.5 in 10,000) and lowest in Hispanics (1 in 10,000). The male to female ratio is 4:1, and the sex imbalance is particularly evident for S-forms (ranging from 4.2 to 5.5 in S-form and from 1.2 to 1.9 in L-form aganglionosis) [1–3] (Table 5.1).

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Authors and Affiliations

  1. Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, 16148, Genova, Italy

    F. Lantieri

  2. Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, 16148, Genova, Italy

    P. Griseri & I. Ceccherini

  3. Unité INSERM U-393 et Université Paris 5, Département de Génétique, Hôpital Necker-Enfants Malades, 75724, Paris, France

    J. Amiel & S. Lyonnet

  4. Scientific Institut (IRCCS), Department of Pediatric Surgery, Policlinico ‘San Matteo’, 27100, Pavia, Italy

    G. Martucciello

  5. U.O. Genetica Medica, Pad. 11, Policlinico S.Orsola-Malpighi, 40138, Bologna, Italy

    G. Romeo

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  1. Immenzaun 6a, 51429, Bergisch Gladbach, Germany

    Alexander Matthias Holschneider

  2. The Children’s Hospital of Cologne, Amsterdamerstr. 59, 50735 , Cologne, Germany

    Alexander Matthias Holschneider

  3. Our Lady’s Children’s Hospital, Children’s Research Centre, University College of Dublin, Crumlin, Dublin 12, Ireland

    Prem Puri

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Lantieri, F. et al. (2008). The Molecular Genetics of Hirschsprung’s Disease. In: Holschneider, A., Puri, P. (eds) Hirschsprung's Disease and Allied Disorders. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-33935-9_5

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