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Cited by 48Genetic and Clinical Aspects of Sex Determination and Chromosomal AbnormalitiesSexual Differentiation and DisordersImmunodeficiency and Autoimmune Disorders

X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood

Fiot, Elodie, Zénaty, Delphine, Boizeau, Priscilla, Haignere, Jérémie, Dos Santos, Sophie, Léger, Juliane, _, _, _, _ +74 more·2019·European Journal of Endocrinology
DOI 10.1530/eje-18-0878
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Abstract

Objective Turner Syndrome is associated with several phenotypic conditions associated with a higher risk of subsequent comorbidity. We aimed to evaluate the prevalence of congenital malformations and the occurrence of age-related comorbid conditions and to determine whether the frequencies of congenital and acquired conditions depend on X chromosome gene dosage, as a function of karyotype subgroup. Design and methods This national retrospective observational cohort study includes 1501 patients. We evaluated the prevalence of congenital malformations and the cumulative incidence of subsequent specific comorbidities at five-year intervals, from the ages of 10 to 30 years, with stratification by karyotype subgroup: 45,X (n = 549), 45,X/46,isoXq (n = 280), 46,X,r(X)/46,XX (n = 106), 45,X/46,XX (n = 221), presence of Y (n = 87). Results Median age was 9.4 (3.7-13.7) years at first evaluation and 16.8 (11.2-21.4) years at last evaluation. Congenital heart (18.9%) malformations were more frequent in 45,X patients, and congenital renal (17.2%) malformations were more frequent in 45,X, 45,X/46,isoXq and 46,X,r(X)/46,XX patients than in those with 45,X/46,XX mosaicism or a Y chromosome (P < 0.0001). The cumulative incidence of subsequent acquired conditions, such as thyroid disease, hearing loss, overweight/obesity, dyslipidemia and, to a lesser extent, celiac disease, glucose intolerance/type 2 diabetes, hypertension and liver dysfunction increased with age, but less markedly for patients with mosaicism than for those with other karyotypes. Patients with a ring chromosome were more prone to metabolic disorders. Conclusion These data suggest that X gene chromosome dosage, particularly for Xp genes, contributes to the risk of developing comorbidities.

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  • Rates of prematurity (birth <37 weeks' gestation) in TS are similar or only slightly higher than the general population (10%-19%), with extreme prematurity uncommon.

    “Rates of prematurity (birth <37 weeks’ gestation) are similar or only slightly higher than the general population (10%-19%), with extreme prematurity uncommon.401,630,631”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [630]

  • Approximately one-third of infants with TS are born small for gestational age (SGA), though the degree of SGA is typically mild, but can be up to 600-1000 g lighter.

    “Approximately one-third of infants with TS are born small for gestational age (SGA), though the degree of SGA is typically mild,630,631 but can be up to 600-1000 g lighter.59”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [630]

  • Karyotypes 45,X, 45,X/46,iso(X), and ring X appear to be at the highest risk for ear and hearing diagnoses, however the incidence rate for ear and hearing diagnoses is 35-fold higher in all TS karyotypes combined compared to the general population.

    “Karyotypes 45,X, 45,X/46,iso(X), and ring X appear to be at the highest risk, however the incidence rate for ear and hearing diagnoses is 35-fold higher in all TS karyotypes combined compared to the general population.630,647”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [630]

  • Overweight/obesity increases from childhood to adulthood in TS, with a cumulative incidence of 8%-60% from age 10 to 30 years.

    “Overweight/obesity increases from childhood to adulthood, with a cumulative incidence of 8%-60% from age 10 to 30 years.630”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [630]

  • Some studies have found an association of metabolic abnormalities with monosomy X, ring X, isochromosome Xq, and Xp deletion, however findings are inconsistent and require more data before clinical interpretation.

    “Some studies have found an association of metabolic abnormalities with monosomy X, ring X, isochromosome Xq, and Xp deletion, however findings are inconsistent and require more data before clinical interpretation.450,630,697,703”

    From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [630]

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Authors
Fiot, E., Zénaty, D., Boizeau, P., Haignere, J., Dos Santos, S., Léger, J., _, _., _, _., Carel, J. C., Cabrol, S., Chanson, P., Christin-Maitre, S., Courtillot, C., Donadille, B., Dulon, J., Houang, M., Nedelcu, M., Netchine, I., Polak, M., Salenave, S., Samara-Boustani, D., Simon, D., Touraine, P., Viaud, M., Bony, H., Braun, K., Desailloud, R., Bertrand, A. M., Mignot, B., Schillo, F., Barat, P., Kerlan, V, Metz, C., Sonnet, E., Reznik, Y., Ribault, V, Carla, H., Tauveron, I., Bensignor, C., Huet, F., Verges, B., Chabre, O., Dupuis, C., Spiteri, A., Cartigny, M., Stuckens, C., Weill, J., Lienhardt, A., Naud-Saudreau, C., Borson-Chazot, F., Brac de la Perriere, A., Pugeat, M., Brue, T., Reynaud, R., Simonin, G., Paris, F., Sultan, C., Leheup, B., Weryha, G., Baron, S., Charbonnel, B., Dubourdieu, S., Baechler, E., Fenichel, P., Wagner, K., Compain, F., Crosnier, H., Personnier, C., Delemer, B., Hecart, A. C., Souchon, P. F., De Kerdanet, M., Galland, F., Nivot-Adamiak, S., Castanet, M., Lecointre, C., Richard, O., Jeandidier, N., Soskin, S., Lecomte, P., Pepin-Donat, M., & Pierre, P.
Affiliations
  • Assistance Publique – Hôpitaux de Paris (FR)
  • Inserm (FR)
  • 1Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, Pediatric Endocrinology Diabetology Department, Reference Centre for Endocrine Growth and Development Diseases, Paris, France
  • Centre Hospitalier Universitaire de Montpellier (FR)
  • Centre Hospitalier Universitaire Amiens-Picardie (FR)
  • Centre Hospitalier Universitaire de Besançon (FR)
  • Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
  • Centre Hospitalier Régional Universitaire de Brest (FR)
  • Centre Hospitalier Universitaire de Caen Normandie (FR)
  • Centre Hospitalier Universitaire de Grenoble (FR)
  • Laboratoire de recherche en cardiovasculaire, métabolisme, diabétologie et nutrition (FR)
  • Centre de Recherche en Cancérologie et Immunologie Intégrée Nantes Angers (FR)
  • Institut de Génétique Humaine (FR)
  • Nutrition-Génétique et Exposition aux Risques Environnementaux (FR)
  • Centre Hospitalier Régional et Universitaire de Nancy (FR)
  • European Organization for Nuclear Research (CH)
  • Centre d’Immunologie de Marseille-Luminy (FR)
  • Différenciation et Communication Neuronale et Neuroendocrine (FR)
  • Laboratoire d'Ingénierie Circulation Transports (FR)
Corresponding author
Léger, Juliane
ORCID
Venue
European Journal of Endocrinology
Publisher
Oxford University Press (OUP)
Published
2019-06
Volume
180
Issue
6
Pages
397-406
ISSN
  • 0804-4643 (ISSN-L)
  • 1479-683X
DOI
10.1530/eje-18-0878
OpenAlex
W2938655862
Cited by
48
References
46
Citations by year
2026: 8 · 2025: 9 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 6 · 2020: 3 · 2019: 1
FWCI
2.55
Type
journal article
Language
en
Open access
closed
Locations
  • European Journal of Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
Keywords
Turner syndrome, congenital malformations, age-related comorbidities, 45,X/46,XX mosaicism, ring chromosomes, congenital heart disease, renal anomalies, thyroid dysfunction, hearing loss, obesity, dyslipidemia, type 2 diabetes, hypertension, liver dysfunction, celiac disease, impaired glucose tolerance
MeSH terms
Congenital Abnormalities, Adolescent, Adult, Age Factors, Child, Female, Heart Defects, Congenital, Humans, Kidney, Kidney Diseases, Mosaicism, Retrospective Studies, Risk Factors, Turner Syndrome, Cohort Studies, Comorbidity, Gene Dosage, Chromosomes, Human, X, Young Adult, Karyotype

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