TY - JOUR
T1 - Genetic testing in the evaluation of individuals with clinical diagnosis of atypical Sturge–Weber syndrome
AU - Yeom, Sang Eun
AU - Cohen, Bernard
AU - Weiss, Clifford R.
AU - Montano, Carolina
AU - Wohler, Elizabeth
AU - Sobreira, Nara
AU - Hammill, Adrienne M.
AU - Comi, Anne
N1 - Funding Information:
The authors thank patients and families who participated in this study.
Publisher Copyright:
© 2023 The Authors. American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.
PY - 2023/4
Y1 - 2023/4
N2 - Sturge–Weber Syndrome (SWS) is a rare vascular malformation disorder characterized by abnormal blood vessels in the brain, skin, and eye. SWS is most commonly caused by a somatic mosaic GNAQ-p.Arg183Gln variant. In this series, 12 patients presented for clinical evaluation of SWS but were noted to have atypical features, and therefore germline and/or somatic genetic testing was performed. Atypical features included extensive capillary malformation on the body as well as the face, frontal bossing, macrocephaly, telangiectasia, overgrowth of extremities, absence of neurologic signs and symptoms, and family history of vascular malformations. Five patients had a somatic GNAQ or GNA11 pathogenic variant, one patient had a somatic mosaic likely-pathogenic variant in PIK3CA, and another one had a somatic mosaic deletion that disrupted PTPRD. The other five patients had germline variants in RASA1, EPHB4, or KIT. Our findings suggest that patients presenting for SWS evaluation who have atypical clinical characteristics may have pathogenic germline or somatic variants in genes other than GNAQ or GNA11. Broad germline and somatic genetic testing in these patients with atypical findings may have implications for medical care, prognosis, and trial eligibility.
AB - Sturge–Weber Syndrome (SWS) is a rare vascular malformation disorder characterized by abnormal blood vessels in the brain, skin, and eye. SWS is most commonly caused by a somatic mosaic GNAQ-p.Arg183Gln variant. In this series, 12 patients presented for clinical evaluation of SWS but were noted to have atypical features, and therefore germline and/or somatic genetic testing was performed. Atypical features included extensive capillary malformation on the body as well as the face, frontal bossing, macrocephaly, telangiectasia, overgrowth of extremities, absence of neurologic signs and symptoms, and family history of vascular malformations. Five patients had a somatic GNAQ or GNA11 pathogenic variant, one patient had a somatic mosaic likely-pathogenic variant in PIK3CA, and another one had a somatic mosaic deletion that disrupted PTPRD. The other five patients had germline variants in RASA1, EPHB4, or KIT. Our findings suggest that patients presenting for SWS evaluation who have atypical clinical characteristics may have pathogenic germline or somatic variants in genes other than GNAQ or GNA11. Broad germline and somatic genetic testing in these patients with atypical findings may have implications for medical care, prognosis, and trial eligibility.
KW - Sturge–Weber syndrome
KW - capillary malformation
KW - genetic testing workflow
KW - vascular malformation
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U2 - 10.1002/ajmg.a.63106
DO - 10.1002/ajmg.a.63106
M3 - Article
C2 - 36710374
AN - SCOPUS:85147306736
SN - 1552-4825
VL - 191
SP - 983
EP - 994
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 4
ER -