Complete Pseudo-Anodontia in an Adult Woman with Pseudo-Hypoparathyroidism Type 1a: A New Additional Nonclassical Feature?

• DOI: 10.3390/diagnostics12122997
• Publication Date: 2022-11-30T12:38:50Z
• Authors: Salvatore Sciacch...; Gian Paolo De Fra...; Maria Piane; Camilla Savio; Claudia De Vitis; Simona Petrucci; Valentina Salvati; Marina Goldoni; Marco Fabiani; Alvaro Mesoraca; Caterina Micolonghi; Barbara Torres; Annalisa Piccinetti; Roberto Pippi; Rita Mancini
• Keywords: GNAS; PHPT-1a; pseudo-anodontia; pseudo-hypoparathyroidism type 1a; pseudo-hypoparathyroidism type 1a; Medicine (General); 03 medical and health sciences; R5-920; 0302 clinical medicine; PHPT-1a; Case Report; pseudo-anodontia; <i>GNAS</i>

Pseudo-anodontia consists in the clinical, not radiographic, absence of teeth, due to failure in their eruption. It has been reported as part of an extremely rare syndrome, named GAPO syndrome. Pseudo-hypoparathyroidism type 1a (PHPT-1a) is a rare condition, characterized by resistance to the parathyroid hormone (PTH), as well as to many other hormones, and resulting in hypocalcemia, hyperphosphatemia, and elevated PTH. We report here the case of a 32-year-old woman with a long-standing history of non-treated hypocalcemia, in the context of an undiagnosed PHPT-1a. She had an intellectual disability, showed clinical features of the Albright hereditary osteodystrophy (AHO) and presented signs of multiple hormone resistances. She received treatment for seizures since the age of six. Examination of her mouth revealed a complete absence of teeth. Treatment of hypocalcemia and hormone deficiencies were started only at 29 years of age. Genetic testing demonstrated the presence of a frameshift variant in the GNAS gene in the proband as well as in her mother. A Single Nucleotide Polymorphism (SNP) array analysis failed to demonstrate pathogenic copy number variants (CNVs) but showed several regions with loss of heterozygosity (LOHs) for a final percentage of 1.75%, compatible with a fifth degree of relationship. Clinical exome sequencing (CES) ruled out any damaging variants in all the teeth agenesis-related genes. In conclusion, although we performed an extensive genetic analysis in search of possible additional gene alterations that could explain the presence of the peculiar phenotypic characteristics observed in our patient, we could not find any additional genetic defects. Our results suggest that the association of genetically confirmed PHPT-1a and complete pseudo-anodontia associated with persistent patchy alopecia areata is a new additional nonclassical feature related to the GNAS pathogenic variant.