View Only- Featuring the 2020 Digital Edition of Cardinal Signs of Common and Uncommon Disorders- OnDemand-PLOD3-related Disorders- Slides

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PLOD3 Disease is a clinically recognizable autosomal recessive collagenopathy characterized by various phenotypic features. It is caused by mutations in the PLOD3 gene, which encodes lysyl hydroxylase 3, an enzyme responsible for post-translational modification of collagens. The disease presents with distinct facial features, visual defects such as cataracts and myopia, musculoskeletal abnormalities including finger contractures and scoliosis, ectodermal manifestations such as reduced palmar creases, developmental delay, below average stature, sensorineural hearing loss, and other complications such as aneurysms and death.<br /><br />The genetic basis of PLOD3 Disease involves biallelic mutations in the PLOD3 gene, resulting in reduced activity of functional domains. To date, 12 different variants have been identified, with most affecting the LH domain of the protein. There is intra- and interfamilial variation in the clinical phenotype.<br /><br />Differential diagnosis of PLOD3 Disease includes Stickler Syndrome, Ehlers-Danlos syndrome, and Osteogenesis Imperfecta. Regular evaluations by various specialists such as physical, occupational, and speech therapists, audiologists, orthopedists, and ophthalmologists are recommended. Imaging evaluations of the vasculature are also important due to the risk of aneurysm/dissection.<br /><br />PLOD3 Disease can now be included in panel testing offered by various companies. It is important to diagnose the condition accurately to manage the associated morbidity and risks. There are insufficient patient numbers to establish a genotype/phenotype correlation. This summary is based on research papers presented at the ACMG Meeting 2020.

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Paul Hillman, MD, PhD

Keywords

PLOD3 Disease

autosomal recessive collagenopathy

PLOD3 gene

lysyl hydroxylase 3

collagen post-translational modification

distinct facial features

visual defects

musculoskeletal abnormalities

ectodermal manifestations

developmental delay