2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Novel Genetic Variant of Weyers Acrofacial Dysostosis with Punctate Epiphyseal Calcifications From Maternal Autoimmune Disease and Review of the Literature

Novel Genetic Variant of Weyers Acrofacial Dysostosis with Punctate Epiphyseal Calcifications From Maternal Autoimmune Disease and Review of the Literature

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This case study describes a novel genetic variant of Weyers Acrofacial Dysostosis with punctate epiphyseal calcifications in a patient with a maternal history of autoimmune disease. The mother had a mixed connective tissue disorder and lupus, with symptoms including Raynaud's phenomenon, inflammatory arthritis, lymphadenopathy, mouth ulcers, and alopecia. She was treated with Prednisone and Plaquenil during pregnancy. The baby was born at 36 weeks gestation with a phenotype characterized by flat nasal bridge, small nares, mid-face hypoplasia, pectus excavatum, and rhizomelic shortening of limbs.<br /><br />The patient exhibited more pronounced short stature, scoliosis, thoracolumbar kyphosis, intermittent knee dislocations, and conductive hearing loss during follow-up. However, their intellectual development was normal. Genetic testing revealed a novel de novo variant in the EVC gene: c.193C>A (p.Leu65Met). This variant is different from previously reported cases of Weyers Acrofacial Dysostosis due to the severity of short stature, absence of nail dystrophy and polydactyly, and the presence of epiphyseal stippling at birth.<br /><br />The study suggests that the patient's clinical phenotype is a combination of Weyers Acrofacial Dysostosis and Chondrodysplasia punctata associated with maternal autoimmune disease. Chondrodysplasia punctata is characterized by abnormal development of fetal bone and cartilage, and maternal autoimmune conditions have been associated with it or its features. The placental crossing of maternal autoantibodies during pregnancy is believed to affect fetal growth plate development and result in punctate lesions in the epiphyses.<br /><br />The case highlights the importance of longitudinal evaluation of genetic patients as features and genetic testing availability may change over time. Overall, this study contributes to the understanding of the genetic and epigenetic factors involved in Weyers Acrofacial Dysostosis and Chondrodysplasia punctata.

Asset Subtitle

Presenting Author - Monika Williams, MD; Co-Author - Muge Gucsavas-Calikoglu, MPH, MD;

Meta Tag

Clinical History

Congenital Anomaly

Dysmorphology

Genetic Testing

Genotype-Phenotype Correlations

Variant Detection

Co-Author Muge Gucsavas-Calikoglu, MPH, MD

Presenting Author Monika Williams, MD

Keywords

Weyers Acrofacial Dysostosis

punctate epiphyseal calcifications

maternal autoimmune disease

genetic testing

EVC gene

short stature

Chondrodysplasia punctata

fetal bone development

autoantibodies

epigenetic factors