New patients with duplication of the pituitary gland-plus syndrome, including a PTCH2 variant and a literature review
Issued Date
2025-01-01
Resource Type
ISSN
00222593
eISSN
14686244
Scopus ID
2-s2.0-105013060657
Journal Title
Journal of Medical Genetics
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Medical Genetics (2025)
Suggested Citation
Buasri K., Pakhathirathien P., Sananmuang T., Dumrongwongsiri S., Thatrimontrichai A., Maneenil G., Khongkraparn A., Ngiwsara L., Sawangareetrakul P., Svasti J., Slavotinek A., Wattanasirichaigoon D. New patients with duplication of the pituitary gland-plus syndrome, including a PTCH2 variant and a literature review. Journal of Medical Genetics (2025). doi:10.1136/jmg-2024-110417 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111732
Title
New patients with duplication of the pituitary gland-plus syndrome, including a PTCH2 variant and a literature review
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Duplication of the pituitary gland (DPG)-plus syndrome is an extremely rare developmental malformation of unknown aetiology. Methods: Two unreported patients of DPG-plus syndrome are described. Underlying genetic defects were explored, including chromosomal microarray (CMA), whole exome sequencing (WES) and mRNA analysis. A literature review was presented. Results: Patient 1 had DPG, palatal cleft, bifid tongue, intraoral teratoma, lingual hamartoma and duplicated basilar artery and odontoid process. Patient 2 had DPG, epignathus teratoma, a nasal mass, choanal atresia, cleft palate, bifid tongue, abnormal basilar artery and fused upper cervical spine. CMA yielded normal results. WES of patient 1 disclosed a novel splice site PTCH2 variant, c.1590+1G>A, leading to exon 12 skipping and an in-frame deletion of 44 amino acids. WES of patient 2 revealed no candidate variants. A literature review of 51 cases showed mostly reported in childhood and female sex (80%). The leading anomalies identified included DPG (100%), cleft palate (68.6%), anomalous cervical spine (56.9%), hypothalamic mass/enlargement (58.8%), intraoral teratoma (58.8%), basilar arterial abnormalities (43.1%) and bifid/trifid tongue (23.5%). Non-craniofacial anomalies were found in <10% of cases. Late complications included precocious puberty, all in female patients, and hypogonadotropic hypogonadism in a few patients. Conclusions: Two new cases of DPG-plus syndrome were reported, with rare findings of epignathus and choanal atresia. We propose that DPG-plus syndrome may result from a double hit in one of the genes involved in SHH signalling, arising from a germline pathogenic variant with mosaicism for a somatic pathogenic variant or digenic/oligogenic inheritance of the SHH signalling-related genes.