Clinical Guidance
ATP6V0A2-related cutis laxa is characterized by generalized cutis laxa, findings associated with generalized connective tissue disorder, developmental delays, and a variety of neurologic findings including abnormality on brain MRI. This disorder spans a phenotypic spectrum that includes the historical diagnoses of Debr-type cutis laxa at the severe end and wrinkly skin syndrome at the mild end; these two phenotypes were thought to be distinct clinical entities until their molecular genetic nature was determined. Children diagnosed in the past with Debr-type cutis laxa had more severe developmental and neurologic abnormalities and a less severe cutaneous phenotype than children diagnosed with wrinkly skin syndrome, in whom the skin showed tighter wrinkles and the changes in facial features were milder . To date, about 80 individuals have been identified with a pathogenic variant in ATP6V0A2 [; Authors, unpublished observations]. The following description of the phenotypic features associated with this condition is based on these reports. Table 2. ATP6V0A2-Related Cutis Laxa: Frequency of Select Features
Feature | % of Persons w/Feature | Comment |
|---|
Cutis laxa | 100% | Combination of fine wrinkles sagging skin; can vanish during childhood. |
Prominent nasal root | 100% | — |
Downslanted palpebral fissures | 100% | Recognizable facial dysmorphism |
Enlarged fontanels w/delayed closure | 100% | — |
Congenital dislocation of hips | 60% | — |
Inguinal hernia | 60% | — |
High myopia | 20% | — |
Other ophthalmic issues | 20% | — |
Developmental delay/Intellectual disability | 100% | Always speech delay; some can attend normal school |
Seizure disorder | 100% | Onset variable; may occur as late as adolescence |
Neurologic decline | Possibly up to 40% | Unclear; few w/follow-up data |
Abnormal brain imaging | 90% | Brain malformation experts can make diagnosis from MRI. Presentation and progression. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. |
Source: GeneReviews — "ATP6V0A2-Related Cutis Laxa"
