Summary of Main Clinical Features of PYCR1-Related ARCL2B
System / Domain Characteristic Features Comments / Notes
Skin & Connective Tissue
Loose, redundant, and inelastic skin (cutis laxa); wrinkled or prematurely aged appearance
Often most prominent on face, neck, and extremities; skin may appear “progeroid” or atrophic
Facial Features
Progeroid facial appearance; prominent forehead; down-slanting palpebral fissures; large, low-set ears; thin lips
Distinctive for ARCL2B and helps distinguish from other ARCL types
Growth & Development
Prenatal and postnatal growth retardation; failure to thrive
Stature often below normal range but survival into adulthood possible
Neurologic / Psychomotor
Developmental delay (mild to moderate), hypotonia, motor delay
Generally milder neurologic impairment than in ALDH18A1-related ARCL2A
Musculoskeletal
Joint hyperlaxity, scoliosis, pectus deformity, slender habitus
Reflects generalized connective-tissue laxity
Ocular
Myopia, keratoconus, strabismus, cataracts (variable)
Not universal but well-documented in several cases
Cranial / Brain Imaging
Mild cortical or cerebellar atrophy in some patients
Brain MRI may be normal or show subtle atrophy
Cardiopulmonary
Occasional mild valvular or pulmonary emphysema-like changes
Rare; much less severe than in other cutis laxa types
Metabolic / Cellular
Evidence of mitochondrial dysfunction and oxidative stress in fibroblasts
Due to impaired proline biosynthesis and redox imbalance
Sparse subcutaneous fat, visible veins, prematurely aged hands
Adds to the “aged” or “De Barsy-like” appearance