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Pseudohypoparathyroidism
Published in Pallavi Iyer, Herbert Chen, Thyroid and Parathyroid Disorders in Children, 2020
Ambika P. Ashraf, Todd D. Nebesio
Categories of PHP and related disorders: PHP type 1A (PHP1A): heterozygous inactivating mutation in the GNAS gene encoding for Gsα is the most common cause of PHP. Loss of maternal imprinting (lack of expression of maternal allele) leads to defective function of Gsα in the target tissues that has maternal tissue-specific imprinting (e.g., proximal renal tubules [PTH], pituitary gland [GHRH], gonads [LH/FSH], and thyroid [TSH]). Features of Albright hereditary osteodystrophy (AHO) are common in PHP1A.PHP type 1B (PHP1B): abnormal patterns of methylation (loss of imprinting) in the differentially methylated regions (DMR) associated with GNAS complex locus at the maternal exon (GNAS A/B: TSS-DMR). There is also a paternal-specific imprinting pattern of GNAS DMR on both alleles resulting in a clinical phenotype characterized by renal resistance to PTH and mild resistance to TSH in the absence of other endocrine or physical abnormalities (no AHO features) and normal Gsα activity.PHP type 1C (PHP1C): lack of expression of maternal allele and characterized by multi-hormone resistance and the presence of signs of AHO. Normal Gsα activity. Considered a variant of PHP type 1A.Pseudopseudohypoparathyroidism (PPHP): paternally derived inactivating mutations in GNAS gene (lack of expression of paternal allele). AHO phenotype occurs in the absence of endocrine abnormalities.Progressive osseous heteroplasia (POH): paternally inherited GNAS inactivating mutations. Characterized by ectopic bone formation in dermis, skeletal muscle, and deep connective tissues. No PTH resistance.Genetic alterations within PRKAR1A and PDE4D: heterozygous point mutations in either gene cause acrodysostosis (brachydactyly involving all phalanxes, metacarpals, and metatarsals), nasal hypoplasia, facial dysostosis, and variable hormone resistance (e.g., PTH and TSH).PHP type 2 (PHP2): molecular defect has not been identified.
Pseudohypoparathyroidism presenting in children at a tertiary hospital in Johannesburg, South Africa
Published in Journal of Endocrinology, Metabolism and Diabetes of South Africa, 2020
N Madi, FY Moosa, KB Parbhoo, JM Pettifor, K Thandrayen
PHP-Ia,-Ib and -Ic are associated with reduced or absent expression/function of the protein Gsα (encoded by the maternal GNAS complex locus). GNAS DMR methylation changes, paternal uniparental isodisomy of chromosome 20q, and small deletions in STX16 are seen in patients with PHPI-b.10,18