GAPO syndrome is an extremely rare genetic disorder characterized by the constellation of growth retardation, alopecia, pseudo-anodontia, and optic atrophy. Since its formal description in 1984 by Tipton and Gorlin, fewer than 40 cases of GAPO syndrome have been identified worldwide. It has an estimated incidence of 1 in 1 million live births with no apparent sex, ethnic, or geographic predilection. Although numerous other diseases overlap clinically with GAPO syndrome, it has a distinct set of features that together provide excellent sensitivity and specificity for clinical diagnosis. The mutations responsible for GAPO syndrome are present at birth. However, the clinical phenotype may not present until later, usually becoming apparent as early as 6 months of age, with the complete clinical picture becoming apparent at 2 years.

GAPO syndrome is caused by mutations in the anthrax toxin receptor 1 gene (ANTXR1; also known as TEM8) and follows an autosomal-recessive inheritance pattern with high phenotypic penetrance and expressivity. The ANTXR1 gene product plays a role in cytoskeletal reorganization and extracellular matrix deposition in fibroblasts and endovascular pericytes in the skin, connective tissues, chondrocytes, and bone. When ANTXR1 is mutated, connective tissue homeostasis is disrupted and uncontrolled extracellular matrix protein accumulation occurs.

Scalp hair, eyebrows, and eyelashes are present at birth but become sparse over time, with hair follicles replaced by fibrosis. Moreover, widespread interstitial fibrosis of the liver, spleen, lungs, heart, kidneys, pancreas, and adrenals frequently occurs, resulting in multi-organ dysfunction and failure. Patients with GAPO syndrome have mental and motor developmental delays and reduced life expectancy of less than 40 years, usually due to atherosclerosis and interstitial lung disease. Pseudo-anodontia is due to failure of tooth eruption through the gums. Progressive bilateral optic nerve atrophy also frequently occurs in patients with GAPO syndrome patients but is a variable feature of the disease.