{
  "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.",
  "authors": [
    {
      "affiliations": [
        "Department of Pediatrics, Mahidol University, Bangkok, Thailand"
      ],
      "name": "Kochakorn Buasri"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Prince of Songkla University, Hat Yai, Thailand"
      ],
      "name": "Pattima Pakhathirathien"
    },
    {
      "affiliations": [
        "Department of Diagnostic and Therapeutic Radiology, Mahidol University, Bangkok, Thailand"
      ],
      "name": "Thiparom Sananmuang"
    },
    {
      "affiliations": [
        "Department of Surgery, Mahidol University, Bangkok, Thailand"
      ],
      "name": "Sarayuth Dumrongwongsiri"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Prince of Songkla University, Hat Yai, Thailand"
      ],
      "name": "Anucha Thatrimontrichai"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Prince of Songkla University, Hat Yai, Thailand"
      ],
      "name": "Gunlawadee Maneenil"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Mahidol University, Bangkok, Thailand"
      ],
      "name": "Arthaporn Khongkraparn"
    },
    {
      "affiliations": [
        "Chulabhorn Research Institute, Bangkok, Thailand"
      ],
      "name": "Lukana Ngiwsara"
    },
    {
      "affiliations": [
        "Chulabhorn Research Institute, Bangkok, Thailand"
      ],
      "name": "Phannee Sawangareetrakul"
    },
    {
      "affiliations": [
        "Chulabhorn Research Institute, Bangkok, Thailand"
      ],
      "name": "Jisnuson Svasti"
    },
    {
      "affiliations": [
        "Cincinnati Children’s Hospital Medical Center Division of Human Genetics, Cincinnati, Ohio, USA",
        "University of Cincinnati, Cincinnati, Ohio, USA"
      ],
      "name": "Anne Slavotinek"
    },
    {
      "affiliations": [
        "Department of Pediatrics, Mahidol University, Bangkok, Thailand"
      ],
      "name": "Duangrurdee Wattanasirichaigoon"
    }
  ],
  "title": "New patients with duplication of the pituitary gland–plus syndrome, including a PTCH2 variant and a literature review",
  "uid": "fe3d3c99-a4d5-5a9c-b65f-edc77da42182"
}