However, defective ATP6V0A2 pumps in the vesicle increase the lumenal pH of the vesicle, leading to premature coacervation and defective elastic fiber assembly. The abnormal assembly and glycosylation of proteins used to make elastic fibers explains the connective tissue phenotypes associated with ARCL2 and WSS but does not explain the neurodevelopmental disorders or growth defects of these patients (18). Elastin is not required for brain or bone growth. However, it is believed that abnormal/impaired secretion of the brain and bone-specific ECM proteins caused by dysregulation of Golgi acidification is what leads to the neural and skeletal defects in ARCL2. Diagnosis
Accurate diagnosis of wrinkly skin syndrome generally requires specialized dermatological assessment. In addition to assessment of clinical physical symptoms, diagnosis may be aided by:
x-rays to identify joint abnormalities
ophthalmologic evaluation of hypertelorism, downslanting eyes, and myopia
brain MRI scans to evaluate the degree of microcephaly
genetic screening for congenital disorders of glycosylation (CDG)
skin biopsy and histological analysis
genetic screening for mutations in the ATP6VOA2 geneThe pigmentation patterns observed in skin biopsies reveal a characteristic lack of elastic fibers in the papillary dermis and clumping of elastic fibers in the reticular dermis. Despite assessment of each of these diagnostic factors, a definitive diagnosis differentiating WSS from cutis laxa requires genetic testing. Differential diagnosis
Several symptoms are shared with cutis laxa type II (CLT2) including wrinkling of skin, microcephaly, and developmental delay which has made proper diagnosis difficult in several cases. However, the severity of skin abnormalities and facial dysmorphia is greater in cutis laxa type II.
In the same year, WSS was established as a new heritable disorder of connective tissue that appeared to be transmitted as an
. In 1993, WSS was diagnosed in a mother and her son. Both patients displayed decreased elastic recoil of the skin and an increase in the number of palmar creases. In 1999, there were up to nine reported cases of WSS. In 2008, Kornak et al. investigated glycosylation of serum proteins with individuals with WSS and found that they had defects in N-glycosylation at the level of the Golgi apparatus. References
NIH GARD (Genetic and Rare Diseases Information Center)
Monarch Initiative
Online Mendelian Inheritance in Man Database

See also
Ehlers–Danlos syndrome
Cutis Laxa Type II
List of cutaneous conditions

References


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