Year: 2026
Type: book
Abstract: Clinical characteristicsNeurocutaneous disorders due to mitochondrial proline synthesis defects comprise PYCR1-related autosomal recessive cutis laxa (ARCL), ALDH18A1-related ARCL, and ALDH18A1-related autosomal dominant cutis laxa (ADCL).These disorders are characterized by thin, translucent skin with wrinkles (especially on the hands and feet); typical facial characteristics including a triangular face with a progeroid appearance, a broad forehead (prominent-appearing neurocranium due to small viscerocranium), convex nasal ridge, full or sagging cheeks, and pointed chin; moderate-to-severe intellectual disability or mild intellectual disability with additional neurodiverse phenotypes including autism spectrum disorder or attention-deficit/hyperactivity disorder; and pre-and postnatal growth deficiency.Additional features can include joint laxity, congenital hypotonia, progressive increased lower limb reflexes/ spasticity, congenital hip dislocation, adducted thumbs, corneal clouding, and lens opacities. Diagnosis/testingThe diagnosis of a neurocutaneous disorder due a to mitochondrial proline synthesis defect can be established in a proband with characteristic clinical findings and identification of biallelic ALDH18A1 or PYCR1 pathogenic variants or a de novo ALDH18A1 pathogenic variant associated with ALDH18A1-related ADCL.
Language: English
Subfield: Clinical Biochemistry
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7142562409