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Eur J Endocrinol. 2016 Mar;174(3):281-8. doi: 10.1530/EJE-15-1000. Epub 2015 Dec 14.

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome.

Author information

1
Assistance Publique-Hôpitaux de ParisHôpital Robert Debré, Service d'Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, INSERM U 1141, 48 Bd Sérurier, F-75019 Paris, FranceUniversité Paris DiderotSorbonne Paris Cité, F-75019 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm)Unité 1141, DHU Protect, F-75019 Paris, FranceAP-HPHôpital Robert Debré, Unit of Clinical Epidemiology, F-75019, Paris, FranceInsermCIC-EC 1426, F-75019 Paris, France.
2
Assistance Publique-Hôpitaux de ParisHôpital Robert Debré, Service d'Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, INSERM U 1141, 48 Bd Sérurier, F-75019 Paris, FranceUniversité Paris DiderotSorbonne Paris Cité, F-75019 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm)Unité 1141, DHU Protect, F-75019 Paris, FranceAP-HPHôpital Robert Debré, Unit of Clinical Epidemiology, F-75019, Paris, FranceInsermCIC-EC 1426, F-75019 Paris, France Assistance Publique-Hôpitaux de ParisHôpital Robert Debré, Service d'Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, INSERM U 1141, 48 Bd Sérurier, F-75019 Paris, FranceUniversité Paris DiderotSorbonne Paris Cité, F-75019 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm)Unité 1141, DHU Protect, F-75019 Paris, FranceAP-HPHôpital Robert Debré, Unit of Clinical Epidemiology, F-75019, Paris, FranceInsermCIC-EC 1426, F-75019 Paris, France.
3
Assistance Publique-Hôpitaux de ParisHôpital Robert Debré, Service d'Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, INSERM U 1141, 48 Bd Sérurier, F-75019 Paris, FranceUniversité Paris DiderotSorbonne Paris Cité, F-75019 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm)Unité 1141, DHU Protect, F-75019 Paris, FranceAP-HPHôpital Robert Debré, Unit of Clinical Epidemiology, F-75019, Paris, FranceInsermCIC-EC 1426, F-75019 Paris, France Assistance Publique-Hôpitaux de ParisHôpital Robert Debré, Service d'Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, INSERM U 1141, 48 Bd Sérurier, F-75019 Paris, FranceUniversité Paris DiderotSorbonne Paris Cité, F-75019 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm)Unité 1141, DHU Protect, F-75019 Paris, FranceAP-HPHôpital Robert Debré, Unit of Clinical Epidemiology, F-75019, Paris, FranceInsermCIC-EC 1426, F-75019 Paris, France Assistance Publique-Hôpitaux de ParisHôpital Robert Debré, Service d'Endocrinologie Diabétologie Pédiatrique, Centre de Référence des Maladies Endocriniennes Rares de la Croissance, INSERM U 1141, 48 Bd Sérurier, F-75019 Paris, FranceUniversité Paris DiderotSorbonne Paris Cité, F-75019 Paris, FranceInstitut National de la Santé et de la Recherche Médicale (Inserm)Unité 1141, DHU Protect, F-75019 Paris, FranceAP-HPHôpital Robert Debré, Unit of Clinical Epidemiology, F-75019, Paris, FranceInsermCIC-EC 1426, F-75019 Paris, France juliane.leger@aphp.fr.

Abstract

OBJECTIVE:

Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment.

DESIGN:

We conducted a national observational multicenter study.

METHODS:

Birth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%).

RESULTS:

Birth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3-11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0-21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome.

CONCLUSION:

These data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy.

PMID:
26744895
DOI:
10.1530/EJE-15-1000
[Indexed for MEDLINE]

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