Clinical characteristics: 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. At birth, hypotonia, overfolded skin, and distinctive facial features are present and enlarged fontanelles are often observed. During childhood, the characteristic facial features and thick or coarse hair may become quite pronounced. The skin findings decrease with age, although easy bruising and Ehlers-Danlos-like scars have been described in some. In most (not all) affected individuals, cortical and cerebellar malformations are observed on brain MRI. Nearly all affected individuals have developmental delays, seizures, and neurologic regression.
Diagnosis/testing: The diagnosis of ATP6V0A2-related cutis laxa is established by the presence of suggestive findings and biallelic pathogenic variants in ATP6V0A2 identified by molecular genetic testing.
Management: Treatment of manifestations: Standard treatment for congenital hip dislocation, inguinal hernias, high myopia, and seizure disorders. Early intervention and management of developmental delays and intellectual disability and psychological help as needed for self-image issues.
Surveillance: Annual ophthalmologic examination, EEG, and monitoring of anticonvulsive drug levels.
Genetic counseling: ATP6V0A2-related cutis laxa is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for an ATP6V0A2 pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Once the ATP6V0A2 pathogenic variants have been identified in an affected family member, carrier testing for at-risk relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing for ATP6V0A2-related cutis laxa are possible.
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