<unk>  has an autosomal recessive pattern of inheritance. 80% of clinical cases of<unk>  have detectable mutations in the ABCC6 gene. Mutations in almost all parts of the gene have been described, of all types (missense, nonsense, splice alteration, insertion, small deletion or large deletion). Although there have been reports of autosomal dominant inheritance, the inheritance is typically autosomal recessive (both parents need to be carriers, and there is a 25% chance that a child will inherit both abnormal copies of the gene and therefore develop the condition). Strong genetic linkage was found with mutations in the ABCC6 gene, which codes for the ABCC6 protein, which is a membrane transporter from the large ATP-binding cassette transporter family. The protein is expressed in most organs, but mainly in the liver and kidney. ABCC6 mediates ATP release in the liver. This is the main source of circulating pyrophosphate (PPi), and individuals affected by<unk>  have strongly reduced plasma PPi levels, explaining their mineralization disorder. One study suggested that mutations causing total absence of an ABCC6 protein caused a more severe disease, but this could not be confirmed in a subsequent case series. Given the variations in age of onset and severity it is likely that other unknown risk factors (genetic, environmental, and lifestyle) may be involved. Premature atherosclerosis is also associated with mutations in the ABCC6 gene, even in those without<unk> . A syndrome almost indistinguishable from hereditary<unk>  has been described in patients with hemoglobinopathies (sickle-cell disease and thalassemia) through a poorly understood mechanism. In addition, there appears to be another<unk> -like syndrome with a similar phenotype but as a result of problems with another gene, gamma-glutamyl carboxylase. Mutations in ABCC6 can also cause generalized arterial calcification of infancy. In some cases of<unk> , mutations in ABCC6 cannot be found, and other genes such as ENPP1 may be implicated
Pseudoxanthoma elasticum
Nodular lichen myxedematosus
Keratosis pilaris
Erythrokeratodermia variabilis
Keratosis pilaris atrophicans
Dystrophic calcinosis cutis
Granuloma annulare
Dermatosis neglecta