OMIM ID:
Pseudoxanthoma Elasticum-Like Disease
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Retinitis pigmentosa has been diagnosed clinically and confirmed by ERG studies in some patients. The fundi in a few individuals have the typical angioid streaks and/or peau d’orange changes. The impact on visual acuity and its prognosis has not been systematically studied.
Systemic Features
The skin changes resulting from fragmentation and aberrant mineralization of connective tissue, particularly elastic fibers, resemble those seem in classic pseudoxanthoma elasticum. These include the presence of yellowish papules or leathery plaques with dot-like depressions (‘chicken skin’). However, the skin changes are more widespread and involve trunk as well as limbs and flexural areas. Ultrastructurally the elastic fibers are more severely fragmented than those in classic PXE.
Many patients in addition have deficiencies in vitamin K-dependent clotting factors such as II, VII, IX, and X. Epistaxis, spontaneous gingival bleeding and severe vaginal hemorrhages may occur. Cerebral aneurysms, vascular occlusions, and atherosclerotic plaques in the lower extremities have been reported in a few patients.
Genetics
Inheritance
Classic pseudoxanthoma elasticum is due to homozygous mutations in the ABCC6 (ATP-binding cassette subfamily C member 6) gene. However, in the PXE-like condition described here homozygous or compound heterozygous mutations in the GGCX (gamma-glutamyl carboxylase) gene (2p11.2) are responsible. Some heterozygous GGCX individuals in families with this genotype who are also heterozygous for ABCC6 mutations (doubly heterozygous) may have similar skin features. Thus the condition described here may also be a digenic disorder in some individuals.
Pseudoxanthoma elasticum-like disease is an autosomal recessive disorder.
Pedigree
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.