Skip to Main content Skip to Navigation
Journal articles

Pituitary stalk interruption syndrome is characterized by genetic heterogeneity

Abstract : Pituitary stalk interruption syndrome is a rare disorder characterized by an absent or ectopic posterior pituitary, interrupted pituitary stalk and anterior pituitary hypoplasia, as well as in some cases, a range of heterogeneous somatic anomalies. A genetic cause is identified in only around 5% of all cases. Here, we define the genetic variants associated with PSIS followed by the same pediatric endocrinologist. Exome sequencing was performed in 52 (33 boys and 19 girls), including 2 familial cases single center pediatric cases, among them associated 36 (69.2%) had associated symptoms or syndromes. We identified rare and novel variants in genes (37 families with 39 individuals) known to be involved in one or more of the following—midline development and/or pituitary development or function ( BMP4 , CDON , GLI2 , GLI3 , HESX1 , KIAA0556 , LHX9 , NKX2-1 , PROP1 , PTCH1 , SHH , TBX19 , TGIF1 ), syndromic and non-syndromic forms of hypogonadotropic hypogonadism ( CCDC141 , CHD7 , FANCA , FANCC , FANCD2 , FANCE , FANCG , IL17RD , KISS1R , NSMF , PMM2 , SEMA3E , WDR11 ), syndromic forms of short stature ( FGFR3 , NBAS , PRMT7 , RAF1 , SLX4 , SMARCA2 , SOX11 ), cerebellum atrophy with optic anomalies ( DNMT1 , NBAS ), axonal migration ( ROBO1 , SLIT2 ), and agenesis of the corpus callosum ( ARID1B , CC2D2A , CEP120 , CSPP1 , DHCR7 , INPP5E , VPS13B , ZNF423 ). Pituitary stalk interruption syndrome is characterized by a complex genetic heterogeneity, that reflects a complex phenotypic heterogeneity. Seizures, intellectual disability, micropenis or cryptorchidism, seen at presentation are usually considered as secondary to the pituitary deficiencies. However, this study shows that they are due to specific gene mutations. PSIS should therefore be considered as part of the phenotypic spectrum of other known genetic syndromes rather than as specific clinical entity.
Document type :
Journal articles
Complete list of metadata
Contributor : Ken McElreavey Connect in order to contact the contributor
Submitted on : Thursday, June 17, 2021 - 2:23:40 PM
Last modification on : Thursday, April 7, 2022 - 10:10:34 AM
Long-term archiving on: : Saturday, September 18, 2021 - 6:38:54 PM


Distributed under a Creative Commons Attribution 4.0 International License




Raja Brauner, Joelle Bignon-Topalovic, Anu Bashamboo, Ken Mcelreavey. Pituitary stalk interruption syndrome is characterized by genetic heterogeneity. PLoS ONE, Public Library of Science, 2020, 15 (12), pp.e0242358. ⟨10.1371/journal.pone.0242358⟩. ⟨pasteur-03263613⟩



Record views


Files downloads