Fibrous dysplasia / McCune-Albright syndrome (FD/MAS), the result of an early embryonic postzygotic somatic activating pathogenic variant in GNAS (encoding the cAMP pathway-associated G-protein, Gsa), is characterized by involvement of the skin, skeleton, and certain endocrine organs. However, because Gsa signaling is ubiquitous, additional tissues may be affected. Café au lait skin macules are common and are usually the first manifestation of the disease, apparent at or shortly after birth. Fibrous dysplasia (FD), which can involve any part and combination of the craniofacial, axial, and/or appendicular skeleton, can range from an isolated, asymptomatic monostotic lesion discovered incidentally to severe disabling polyostotic disease involving practically the entire skeleton and leading to progressive scoliosis, facial deformity, and loss of mobility, vision, and/or hearing. Endocrinopathies include: Gonadotropin-independent precocious puberty resulting from recurrent ovarian cysts in girls and autonomous testosterone production in boys; Testicular lesions with or without associated gonadotropin-independent precocious puberty; Thyroid lesions with or without non-autoimmune hyperthyroidism; Growth hormone excess; FGF23-mediated phosphate wasting with or without hypophosphatemia in association with fibrous dysplasia; and Neonatal hypercortisolism. The prognosis for individuals with FD/MAS is based on disease location and severity.

Familial isolated glucocorticoid deficiency (GCCD) is an adrenocortical failure characterized by very low levels of plasma cortisol despite high levels of plasma adrenocorticotropin (ACTH). Moreover, the adrenal response to ACTH is severely impaired. There is no mineralocorticoid deficiency and the renin-angiotensin system is not affected (summary by Genin et al., 2002). For a general phenotypic description and a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200).

Familial glucocorticoid deficiency (GCCD) is a rare autosomal recessive disorder characterized by an inability of the adrenal cortex to produce cortisol in response to stimulation by adrenocorticotropic hormone (ACTH). Affected individuals typically present within the first few months of life with symptoms related to cortisol deficiency, including failure to thrive, recurrent illnesses or infections, hypoglycemia, convulsions, and shock. The disease is life-threatening if untreated (summary by Meimaridou et al., 2012). For a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200).

Familial glucocorticoid deficiency (GCCD) is an autosomal recessive disorder resulting from defects in the action of adrenocorticotropic hormone (ACTH) to stimulate glucocorticoid synthesis in the adrenal. Production of mineralocorticoids by the adrenal is normal. Patients present in early life with low or undetectable cortisol and, because of the failure of the negative feedback loop to the pituitary and hypothalamus, grossly elevated ACTH levels (summary by Clark et al., 2009). Genetic Heterogeneity of Familial Glucocorticoid Deficiency Familial glucocorticoid deficiency-2 (GCCD2; 607398) is caused by mutation in the MRAP gene (609196) on chromosome 21q22. GCCD3 (609197) has been mapped to chromosome 8q11.2-q13.2. GCCD4 with or without mineralocorticoid deficiency (614736) is caused by mutation in the NNT gene (607878) on chromosome 5p12. GCCD5 (617825) is caused by mutation in the TXNRD2 gene (606448) on chromosome 22q11.

Familial glucocorticoid deficiency is an autosomal recessive disorder resulting from resistance to the action of adrenocorticotropin (ACTH) on the adrenal cortex, which stimulates glucocorticoid production. Affected individuals are deficient in cortisol and, if untreated, are likely to succumb to hypoglycemia or overwhelming infection in infancy or childhood (summary by Metherell et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of familial glucocorticoid deficiency, see GCCD1 (202200).

Autosomal dominant tubulointerstitial kidney disease-5 (ADTKD5) is characterized by the onset of progressive chronic renal disease in the first decades of life. Mild hyperuricemia may be present, but gout, hypertension, and proteinuria are usually absent. The disease may be associated with anemia or neutropenia. Some patients may have additional findings, including poor overall growth and impaired cognitive function. Renal biopsy shows tubulointerstitial abnormalities with atrophic tubules and fibrosis; secondary glomerular abnormalities and simple cysts may also be present (summary by Bolar et al., 2016). For a discussion of genetic heterogeneity and revised nomenclature of ADTKD, see ADTKD1 (162000).