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.
For more information, see OMIM.
H47.22 – Hereditary optic atrophy
K00.8 – Other disorders of tooth development
Q84.0 – Congenital alopecia
R62.59 – Other lack of expected normal physiological development in childhood
721843003 – Growth retardation, alopecia, pseudoanodontia, optic atrophy syndrome