Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms

Abstract

Background: Pituitary stalk interruption syndrome (PSIS) is a particular entity in the population of patients with hypopituitarism. Only rare cases have a known genetic cause. Objectives: i) To compare subgroups with or without extra-pituitary malformations (EPM) in a cohort of PSIS patients to identify predictive factors of evolution, ii) to determine the incidence of mutations of the known pituitary transcription factor genes in PSIS. Study design: We analyzed features of 83 PSIS patients from 80 pedigrees and screened HESX1, LHX4, OTX2, and SOX3 genes. Results: PSIS had a male predominance and was rarely familial (5%). Pituitary hypoplasia was observed only in the group with EPM. Multiple hormone deficits were observed significantly more often with versus without EPM (87.5 vs 69.5% respectively). Posterior pituitary location along the stalk was a significant protective factor regarding severity of hormonal phenotype. A novel HESX1 causative mutation was found in a consanguineous family, and two LHX4 mutations were present in familial PSIS. Conclusion: PSIS patients with EPM had a more severe hormonal disorder and pituitary imaging status, suggesting an antenatal origin. HESX1 or LHX4 mutations accounted for !5% of cases and were found in consanguineous or familial cases.

Effect of transcription factor ZBTB20 on mouse pituitary development

“…Scholars have gained some knowledge about the regulation of pituitary development; however, the exact mechanism of this process remains unclear. As even a single change in known signaling molecules and transcriptional factors can induce various phenotype and hormone level variations, a greater number of pituitary development-related genes must be investigated further (Reynaud et al, 2011). Previous in vivo studies have demonstrated that the ZBTB20 transcriptional factor, expressed in the pituitary gland, plays a critical role in mouse development (Shillingford et al, 2003).…”

Hypoglycémie néonatale sévère et récidivante sans perte de sel révélatrice d’un syndrome de résistance à l’ACTH

“…Ce bilan doit être systématique en l'absence de facteurs de risques ou si l'hypoglycémie persiste au-delà de la durée prévisible. [ ( F i g u r e _ 2 ) T D $ F I G ] néonatale immédiate, 16 % avaient eu des hypoglycémies néonatales et 5 % un ictère non exploré [9]. Malgré ces symptômes, le diagnostic de déficit hypophysaire congénital avait été tardif (âge moyen : 9,6 ans) survenant seulement lorsque le retard de croissance était devenu sévère (taille moyenne : -3,5 AE 1 SDS).…”

Pilot Neonatal Screening Program for Central Congenital Hypothyroidism: Evidence of Significant Detection

“…All coding exons and intron region boundaries of these genes were amplified from genomic DNA as previously described using exon-flanking primers (sequence posted online) [20]. …”