SEARCHCASE_REPORTpediatric ophthalmology, endocrinology

case_report·pediatric ophthalmology, endocrinology, pediatrics, neurology, ophthalmology·PMC10721018

Exome sequencing in 16 patients with pituitary stalk interruption syndrome: A monocentric study

PLOS ONE · 8 authors, 3 centres

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TL;DR

The study details clinical phenotypes, pituitary hormone deficiencies, and associated anomalies (e.g., ophthalmic disorders in 37.5% of cases).

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The study details clinical phenotypes, pituitary hormone deficiencies, and associated anomalies (e.g., ophthalmic disorders in 37.5% of cases). The authors conclude that the diagnostic yield for isolated PSIS is low and that a major challenge remains in identifying definitive pathogenic variants for such cases.

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case_report

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pediatric ophthalmology

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ORIGINAL PAPER

PMC10721018

Exome sequencing in 16 patients with pituitary stalk interruption syndrome: A monocentric study

PLOS ONE

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ABSTRACT

Pituitary stalk interruption syndrome (PSIS) is a rare disorder characterized by an absent or ectopic posterior pituitary, absent or interrupted pituitary stalk and anterior pituitary hypoplasia on magnetic resonance imaging (MRI), as well in some cases a range of heterogeneous somatic anomalies. The triad can be incomplete. Here, we performed exome sequencing on 16 sporadic patients, aged 0.4 to 13.7 years diagnosed with isolated or complex PSIS. Growth hormone deficiency was isolated in 10 cases, or associated with thyrotropin deficiency in 6 others (isolated (2 cases), associated with adrenocorticotropin deficiency (1 case), gonadotropins deficiency (1 case), or multiple deficiencies (2 cases)). Additional phenotypic anomalies were present in six cases (37.5%) including four with ophthalmic disorders. In 13 patients variants were identified that may contribute to the phenotype. However, only a single individual carried a variant classified as pathogenic. This child presented with the typical clinical presentation of Okur-Chung neurodevelopmental syndrome due to a CSNK2A1 missense variant. We also identified variants in the holoprosencephaly associated genes GLI2 and PTCH1 . A likely pathogenic novel splice site variant in the GLI2 gene was observed in a child with PSIS and megacisterna magna. In the remaining 11 cases 26 variants in genes associated with pituitary development or function were identified and were classified of unknown significance. Compared with syndromic forms the diagnostic yield in the isolated forms of PSIS is low. Although we identified rare or novel missense variants in several hypogonadotropic hypogonadism genes (e.g. FGF17 , HS6ST1 , KISS1R , CHD7 , IL17RD ) definitively linking them to the PSIS phenotype is premature. A major challenge remains to identify pathogenic variants in cases with isolated PSIS.

CITATION EXPORT

Raja Brauner, Joelle Bignon-Topalovic, Anu Bashamboo et al.. Exome sequencing in 16 patients with pituitary stalk interruption syndrome: A monocentric study. PLOS ONE. (2023). https://doi.org/10.1371/journal.pone.0292664

AUTHORS

8 · 3 CENTRES

Raja Brauner, Joelle Bignon-Topalovic, Anu Bashamboo, Ken McElreavey, Nejat Mahdieh, Nejat Mahdieh, Nejat Mahdieh, Nejat Mahdieh

1 Pediatric Endocrinology Unit, Hôpital Fondation Adolphe de Rothschild and Université Paris Cité, Paris, France
2 Human Developmental Genetic Unit, Institut Pasteur, Paris, France
Shaheed Rajaei Hospital: Rajaie Cardiovascular Medical and Research Center, ISLAMIC REPUBLIC OF IRAN

EDITOR / REVIEWER

Nejat Mahdieh