GNA11 brain somatic pathogenic variant in an individual with phacomatosis pigmentovascularis

Joseph M Sliepka; Sarah C McGriff; Linda Z Rossetti; Peyman Bizargity; Haley Streff; Yi-Shan Lee; Hongzheng Dai; Satyamaanasa Polubothu; Grace Lee; Vicky Ren; Jill V Hunter; Daniel J Curry; Fernando Scaglia; Adekunle M Adesina; Irfan Ali; Veronica Kinsler; Lindsay C Burrage; Dana Marafi

doi:10.1212/NXG.0000000000000366

GNA11 brain somatic pathogenic variant in an individual with phacomatosis pigmentovascularis

Neurol Genet. 2019 Oct 30;5(6):e366. doi: 10.1212/NXG.0000000000000366. eCollection 2019 Dec.

Authors

Joseph M Sliepka¹, Sarah C McGriff¹, Linda Z Rossetti¹, Peyman Bizargity¹, Haley Streff¹, Yi-Shan Lee¹, Hongzheng Dai¹, Satyamaanasa Polubothu¹, Grace Lee¹, Vicky Ren¹, Jill V Hunter¹, Daniel J Curry¹, Fernando Scaglia¹, Adekunle M Adesina¹, Irfan Ali¹, Veronica Kinsler¹, Lindsay C Burrage¹, Dana Marafi¹

Affiliation

¹ Baylor College of Medicine (J.M.S., S.C.M.), Houston, TX; Texas Children's Hospital (L.Z.R., H.S., G.L., V.R., J.V.H., D.J.C., F.S., A.M.A., I.A., L.C.B., D.M.); Department of Molecular and Human Genetics (L.Z.R., H.S., H.D., F.S., L.C.B., D.M.), Baylor College of Medicine, Houston, TX; Department of Pediatrics (P.B.), Northwell Health, Division of Human Genetics and Genomics, Great Neck, NY; Department of Pathology and Immunology (Y.-S.L.), Washington University School of Medicine, St. Louis, MO; Genetics and Genomic Medicine (S.P., V.K.), UCL GOS Institute of Child Health; Pediatric Dermatology (S.P., V.K.), Great Ormond Street Hospital for Children, London, UK; Department of Dermatology (G.L., V.R.), Department of Radiology (J.V.H.), and Department of Neurosurgery (D.J.C.), Baylor College of Medicine, Houston, TX; Joint BCM-CUHK Center of Medical Genetics (F.S.), Prince of Wales Hospital, ShaTin, Hong Kong SAR; Department of Pathology and Immunology (A.M.A), Department of Pediatrics (I.A.), and Department of Neurology (I.A.), Baylor College of Medicine, Houston, TX; and Department of Pediatrics (D.M.), Faculty of Medicine, Kuwait University, Safat, Kuwait.

Abstract

Objective: To describe the findings of histopathology and genotyping studies in affected brain tissue from an individual with phacomatosis pigmentovascularis (PPV).

Methods: A retrospective chart review of a 2-year 10-month-old male with a clinical diagnosis of PPV cesiomarmorata (or type V) was performed. Clinical features, brain imaging and histopathology findings, and genotyping studies in his affected brain tissue are summarized.

Results: The proband had a clinically severe neurologic phenotype characterized by global developmental delay, generalized hypotonia, and recurrent episodes of cardiac asystole in the setting of status epilepticus. A somatic pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys) was detected in his skin tissue but not in blood (previously published). He underwent an urgent left posterior quadrantectomy for his life-threatening seizures. Histopathology of resected brain tissue showed an increase in leptomeningeal melanocytes and abnormal vasculature, and the exact pathogenic variant in GNA11 (c.547C>T, p.Arg183Cys), previously isolated from his skin tissue but not blood, was detected in his resected brain tissue.

Conclusions: The finding of this variant in affected skin and brain tissue of our patient with PPV supports a unifying genetic diagnosis of his neurocutaneous features.