Table 4.

Classification of PHP and Related Disorders

	Molecular Defect	Parental Origin of GNAS Mutation	Endocrine Defects	Clinical Features	Other Features
PHP1A	Heterozygous mutations in GNAS gene that reduce expression or function of Gαs	Maternal	Multihormone resistancea	1. AHOb; 2. early onset obesity	Cognitive disability, short stature
PPHP	Heterozygous mutations in GNAS gene	Paternal	None	AHO	Small for gestational age at birth, short stature
PHP1C	Heterozygous mutations in GNAS that reduce expression or function of Gs	Maternal	Multihormone resistance	1. AHO; 2. early onset obesity	Cognitive disability, short stature
Familial PHP1B	Heterozygous deletions in STX16, NESP55, and/or AS exons	Maternal	PTH resistance, partial resistance to TSH or other hormones in some	Mild brachydactyly in some	Loss of methylation at GNAS exon A/B
Sporadic PHP1B	Paternal UPD of chromosome 20q in some, but most cases are unresolved	N/A	PTH resistance, partial resistance to TSH or other hormones in some	Mild brachydactyly in some	Methylation defect affecting all four GNAS DMRs
Progressive osseous heteroplasia	Heterozygous mutations in GNAS gene that reduce expression or function of Gαs	Paternal	None	Progressive heterotopic ossification extending to deep connective tissues
Osteoma cutis	Heterozygous mutations in GNAS gene that reduce expression or function of Gαs	Paternal	None	Heterotopic ossification that is limited to dermis and subcutaneous tissues
PHP type 2	None known	N/A	PTH resistance	Severe hypocalcemia	Vitamin D deficiency
Acrodysostosis type 1	PRKAR1A	N/A	TSH and PTH resistance	Brachydactyly and facial dysostosis	Obesity
Acrodysostosis type 2	PDE4D	N/A	None or mild PTH resistance	Brachydactyly and facial dysostosis	No obesity

Abbreviation: N/A, not available; UPD, uniparental disomy.

^aMultiple hormone resistance, resistance to PTH, TSH, and GHRH, and often to gonadotropins as well.

^bAHO comprising round face, short stature, brachydactyly/brachymetacarpia, and heterotopic ossification.