Novel Variant in Exon 3 of the BMP4 Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb Anomaly

Introduction. Pituitary differentiation involves a large number of transcription factors. In particular, BMP4 expression is fundamental for pituitary gland commitment from the ventral diencephalon, suppressing Shh expression in Rathke’s pouch. Pathogenic variants in BMP4 are reported in the literatu...

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Main Authors: Valeria Calcaterra, Rossella Lamberti, Claudia Viggiano, Paola Baldassarre, Luigina Spaccini, Rosa Maria Alfano, Giana Izzo, Laura Grazia Valentini, Gianvincenzo Zuccotti
Format: Article
Language:English
Published: Wiley 2022-01-01
Series:Case Reports in Pediatrics
Online Access:http://dx.doi.org/10.1155/2022/8059409
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author Valeria Calcaterra
Rossella Lamberti
Claudia Viggiano
Paola Baldassarre
Luigina Spaccini
Rosa Maria Alfano
Giana Izzo
Laura Grazia Valentini
Gianvincenzo Zuccotti
author_facet Valeria Calcaterra
Rossella Lamberti
Claudia Viggiano
Paola Baldassarre
Luigina Spaccini
Rosa Maria Alfano
Giana Izzo
Laura Grazia Valentini
Gianvincenzo Zuccotti
author_sort Valeria Calcaterra
collection DOAJ
description Introduction. Pituitary differentiation involves a large number of transcription factors. In particular, BMP4 expression is fundamental for pituitary gland commitment from the ventral diencephalon, suppressing Shh expression in Rathke’s pouch. Pathogenic variants in BMP4 are reported in the literature with a broad phenotypic spectrum, including pituitary and brain malformations. Case Presentation. A five-year-old girl came to medical attention following a mild cervical trauma with onset of cervical pain. On clinical examination at birth, postaxial polydactyly type B of the left hand was observed and removed at 10 months of age. A cervical radiography was performed, and a suspicion of craniocervical junction malformation was made. A magnetic resonance imaging of the cervical spine was made, showing an ectopic posterior pituitary, associated with dysmorphism of the craniocervical junction. The anthropometric parameters were pubertal Tanner stage 1, weight 16 kg (z-score: −1.09), height 107 cm (z-score: −0.76), and BMI 14 kg/m2 (z-score: −0.92). Normal hormonal assessment was detected. Genetic analysis via next generation sequencing showed a novel de novo heterozygous variant (c.277 G > T, p.Glu93∗) in exon 3 of BMP4. Discussion. We described a novel mutation in BMP4, resulting in ectopic posterior pituitary with normal hormonal assessment, associated to craniocervical junction dysmorphism and limb anomaly. It is important to monitor patient’s growth and puberty and to screen the onset of symptoms related to the deficiency of one or more anterior as well as posterior pituitary hormones.
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spelling doaj-art-9c8d6aeba6844352bdd74ac7d03a7cd72025-08-20T02:18:28ZengWileyCase Reports in Pediatrics2090-68112022-01-01202210.1155/2022/8059409Novel Variant in Exon 3 of the BMP4 Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb AnomalyValeria Calcaterra0Rossella Lamberti1Claudia Viggiano2Paola Baldassarre3Luigina Spaccini4Rosa Maria Alfano5Giana Izzo6Laura Grazia Valentini7Gianvincenzo Zuccotti8Pediatric and Adolescent UnitDepartment of PediatricsDepartment of PediatricsDepartment of PediatricsClinical Genetics UnitHuman PathologyPediatric Radiology and Neuroradiology UnitDepartment of NeurosurgeryDepartment of PediatricsIntroduction. Pituitary differentiation involves a large number of transcription factors. In particular, BMP4 expression is fundamental for pituitary gland commitment from the ventral diencephalon, suppressing Shh expression in Rathke’s pouch. Pathogenic variants in BMP4 are reported in the literature with a broad phenotypic spectrum, including pituitary and brain malformations. Case Presentation. A five-year-old girl came to medical attention following a mild cervical trauma with onset of cervical pain. On clinical examination at birth, postaxial polydactyly type B of the left hand was observed and removed at 10 months of age. A cervical radiography was performed, and a suspicion of craniocervical junction malformation was made. A magnetic resonance imaging of the cervical spine was made, showing an ectopic posterior pituitary, associated with dysmorphism of the craniocervical junction. The anthropometric parameters were pubertal Tanner stage 1, weight 16 kg (z-score: −1.09), height 107 cm (z-score: −0.76), and BMI 14 kg/m2 (z-score: −0.92). Normal hormonal assessment was detected. Genetic analysis via next generation sequencing showed a novel de novo heterozygous variant (c.277 G > T, p.Glu93∗) in exon 3 of BMP4. Discussion. We described a novel mutation in BMP4, resulting in ectopic posterior pituitary with normal hormonal assessment, associated to craniocervical junction dysmorphism and limb anomaly. It is important to monitor patient’s growth and puberty and to screen the onset of symptoms related to the deficiency of one or more anterior as well as posterior pituitary hormones.http://dx.doi.org/10.1155/2022/8059409
spellingShingle Valeria Calcaterra
Rossella Lamberti
Claudia Viggiano
Paola Baldassarre
Luigina Spaccini
Rosa Maria Alfano
Giana Izzo
Laura Grazia Valentini
Gianvincenzo Zuccotti
Novel Variant in Exon 3 of the BMP4 Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb Anomaly
Case Reports in Pediatrics
title Novel Variant in Exon 3 of the BMP4 Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb Anomaly
title_full Novel Variant in Exon 3 of the BMP4 Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb Anomaly
title_fullStr Novel Variant in Exon 3 of the BMP4 Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb Anomaly
title_full_unstemmed Novel Variant in Exon 3 of the BMP4 Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb Anomaly
title_short Novel Variant in Exon 3 of the BMP4 Gene Resulted in Ectopic Posterior Pituitary, Craniocervical Junction Dysmorphism and Limb Anomaly
title_sort novel variant in exon 3 of the bmp4 gene resulted in ectopic posterior pituitary craniocervical junction dysmorphism and limb anomaly
url http://dx.doi.org/10.1155/2022/8059409
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