Pituitary stalk interruption syndrome

Voutetakis, Antonis

doi:10.1016/b978-0-12-820683-6.00002-6

Cited by 9 publications

(3 citation statements)

References 176 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aside from ciliogenesis, FUZ is also a Planar Cell Polarity (PCP) pathway effector, a pathway which we have previously examined in the pituitary in the context of receptor‐ligand FAT/DCHS protocadherins. Mutations in FAT/DCHS family result in pituitary phenotypes ranging from morphological defects of the anterior pituitary, interrupted pituitary stalk and ectopic posterior pituitary (Lodge et al, 2020 and see Voutetakis, 2021 for comprehensive review on pituitary stalk anomalies). However, these phenotypes do not overlap with what we see in Fuz −/− mutations, which appear consistent with defects in SHH signalling rather than PCP defects.…”

Section: Discussionmentioning

confidence: 99%

The Fuzzy planar cell polarity protein (FUZ), necessary for primary cilium formation, is essential for pituitary development

Lodge,

Barrell,

Liu

et al. 2023

Journal of Anatomy

View full text Add to dashboard Cite

The primary cilium is an essential organelle that is important for normal cell signalling during development and homeostasis but its role in pituitary development has not been reported. The primary cilium facilitates signal transduction for multiple pathways, the best‐characterised being the SHH pathway, which is known to be necessary for correct pituitary gland development. FUZ is a planar cell polarity (PCP) effector that is essential for normal ciliogenesis, where the primary cilia of Fuz−/−mutants are shorter or non‐functional. FUZ is part of a group of proteins required for recruiting retrograde intraflagellar transport proteins to the base of the organelle. Previous work has reported ciliopathy phenotypes in Fuz−/− homozygous null mouse mutants, including neural tube defects, craniofacial abnormalities, and polydactyly, alongside PCP defects including kinked/curly tails and heart defects. Interestingly, the pituitary gland was reported to be missing in Fuz−/− mutants at 14.5 dpc but the mechanisms underlying this phenotype were not investigated. Here, we have analysed the pituitary development of Fuz−/− mutants. Histological analyses reveal that Rathke's pouch (RP) is initially induced normally but is not specified and fails to express LHX3, resulting in hypoplasia and apoptosis. Characterisation of SHH signalling reveals reduced pathway activation in Fuz−/− mutant relative to control embryos, leading to deficient specification of anterior pituitary fate. Analyses of the key developmental signals FGF8 and BMP4, which are influenced by SHH, reveal abnormal patterning in the ventral diencephalon, contributing further to abnormal RP development. Taken together, our analyses suggest that primary cilia are required for normal pituitary specification through SHH signalling.

show abstract

Section: Discussionmentioning

confidence: 99%

The Fuzzy planar cell polarity protein (FUZ), necessary for primary cilium formation, is essential for pituitary development

Lodge,

Barrell,

Liu

et al. 2023

Journal of Anatomy

View full text Add to dashboard Cite

show abstract

“…There is evidence supporting a role for ciliopathy genes in pituitary gland development and function [76,77]. Within our candidate gene list are seven genes related to cilia function, Mks1, B9d2, Rpgrip1l, Cc2d2a, Ehd1, Sh3pxd2a, and Ezr.…”

Section: Cilia Proteins With Potential Roles In Pituitary Gland Functionmentioning

confidence: 99%

Knockout mice with pituitary malformations help identify human cases of hypopituitarism

Martinez-Mayer,

Brinkmeier,

O’Connell

et al. 2024

Genome Med

View full text Add to dashboard Cite

Background Congenital hypopituitarism (CH) and its associated syndromes, septo-optic dysplasia (SOD) and holoprosencephaly (HPE), are midline defects that cause significant morbidity for affected people. Variants in 67 genes are associated with CH, but a vast majority of CH cases lack a genetic diagnosis. Whole exome and whole genome sequencing of CH patients identifies sequence variants in genes known to cause CH, and in new candidate genes, but many of these are variants of uncertain significance (VUS). Methods The International Mouse Phenotyping Consortium (IMPC) is an effort to establish gene function by knocking-out all genes in the mouse genome and generating corresponding phenotype data. We used mouse embryonic imaging data generated by the Deciphering Mechanisms of Developmental Disorders (DMDD) project to screen 209 embryonic lethal and sub-viable knockout mouse lines for pituitary malformations. Results Of the 209 knockout mouse lines, we identified 51 that have embryonic pituitary malformations. These genes not only represent new candidates for CH, but also reveal new molecular pathways not previously associated with pituitary organogenesis. We used this list of candidate genes to mine whole exome sequencing data of a cohort of patients with CH, and we identified variants in two unrelated cases for two genes, MORC2 and SETD5, with CH and other syndromic features. Conclusions The screening and analysis of IMPC phenotyping data provide proof-of-principle that recessive lethal mouse mutants generated by the knockout mouse project are an excellent source of candidate genes for congenital hypopituitarism in children.

show abstract

“…The incidence is rarely reported as 0.5 in every 100,000 live births [ 2 ], with a male predominance proposing X-linked inheritance [ 3 ]. The exact etiology is uncertain; there is thought to be an association with breech presentation, difficult or prolonged labor, forceps delivery, or birth trauma [ 4 ]. More recent studies have, however, proposed molecular defects in genes concerned with the development of the pituitary to be the cause of this syndrome [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Lost Connection: A Case Report of Interrupted Pituitary Stalk Syndrome

Idrees,

Malik,

Cheema

et al. 2024

Cureus

View full text Add to dashboard Cite

Pituitary stalk interruption syndrome is a triad of thin (<1 mm) or complete absence of the pituitary stalk with either an aplastic or ectopic posterior lobe of the pituitary gland and a hypoplastic or absent anterior lobe of the pituitary. Patients present with growth retardation, short height, seizures, intellectual disability, and absence of sexual maturation at the expected time. Here, we presented a case of a 12-year-old male with stunted growth. Upon examination, there was reduced height, more than 3 standard deviations below the average for his chronological age. Laboratory results showed reduced levels of growth hormone and thyrotropin. Dual-energy X-ray absorptiometry revealed osteoporosis, while an X-ray of the wrist for bone age corresponded to seven years. MRI imaging confirmed the classical triad of findings for pituitary stalk interruption syndrome. Consequently, the patient was referred back to the endocrinology clinic for further management.

show abstract

Pituitary stalk interruption syndrome

Cited by 9 publications

References 176 publications

The Fuzzy planar cell polarity protein (FUZ), necessary for primary cilium formation, is essential for pituitary development

The Fuzzy planar cell polarity protein (FUZ), necessary for primary cilium formation, is essential for pituitary development

Knockout mice with pituitary malformations help identify human cases of hypopituitarism

Lost Connection: A Case Report of Interrupted Pituitary Stalk Syndrome

Contact Info

Product

Resources

About