OMIM ID:
Ehlers-Danlos Syndrome, Type VIA
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
The globe is thin and fragile and ruptures easily. This results from scleral fragility which is in contrast to type VIB EDS (229200) in which the cornea seems to be more fragile. Retinal detachment is always a risk but no quantitative assessment can be made since early case reports did not always provide good classification of EDS types. Other ocular abnormalities such as keratoconus and structural changes in the cornea are less common but frequent changes in classification and lack of genotyping in early cases make definitive clinical correlations difficult.
Systemic Features
The primary clinical manifestations of this form (VIA) of Ehlers-Danlos syndrome are extraocular. The skin is soft, thin, easily extensible, and bruises easily. The joints are highly flexible with a tendency to dislocate. Arterial ruptures are not uncommon, often with severe consequences. Scoliosis begins almost at birth and often progresses to severe kyphoscoliosis. Patients are floppy (hypotonic). Intellect is normal and there are generally no developmental delays. Thirty per cent of infants have a club foot at birth.
Genetics
Inheritance
This an autosomal recessive disorder caused by molecular defects in the PLOD1 gene (1p36.3-p36.2). The gene product is an enzyme, lysyl hydroxylase 1, important for the normal crosslinking of collagen. Mutations in PLOD1 may result in hydroxylase dysfunction with abnormal hydroxylation of lysine, weakened crosslinks, and fragile tissue.
The classification of Ehlers-Danlos disease is under constant revision as new mutations and clinical subtypes are found (see 130000).
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.