Early diagnosis enabling precision medicine treatment in a young boy with PIK3R1-related overgrowth
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Early diagnosis enabling precision medicine treatment in a young boy with PIK3R1-related overgrowth. / Schönewolf-Greulich, Bitten; Karstensen, Helena Gásdal; Hjortshøj, Tina D.; Jørgensen, Finn Stener; Harder, Katja M.; Frevert, Susanne; Hove, Hanne; Diness, Birgitte R.
I: European Journal of Medical Genetics, Bind 65, Nr. 10, 104590, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Early diagnosis enabling precision medicine treatment in a young boy with PIK3R1-related overgrowth
AU - Schönewolf-Greulich, Bitten
AU - Karstensen, Helena Gásdal
AU - Hjortshøj, Tina D.
AU - Jørgensen, Finn Stener
AU - Harder, Katja M.
AU - Frevert, Susanne
AU - Hove, Hanne
AU - Diness, Birgitte R.
N1 - Publisher Copyright: © 2022
PY - 2022
Y1 - 2022
N2 - Mosaic PIK3R1 variants have recently been demonstrated in patients with complex vascular malformations and overgrowth in a syndrome resembling PIK3CA-related overgrowth syndrome (PROS). The PIK3CA-inhibitor, alpelisib, seems to be a promising treatment option for PROS patients. We describe a young boy with overgrowth and a pathogenic mosaic variant in PIK3R1; c.1699A > G, p.(Lys567Glu). He was prenatally suspected of a syndrome on the presence of unusual transient fluctuating subcutaneous edemas and lymphedema of his left shoulder. The pathogenic variant, later found to be causative, was below detection threshold in whole-genome sequencing (WGS) analysis of amniotic fluid. Upon delivery a mosaic pathogenic PIK3R1 variant, was identified by whole-exome sequencing (WES) of a skin biopsy. With no proven treatment options available, and based on the theoretical disease mechanism, alpelisib therapy was initiated at nine months of age. In the first year of treatment growth normalized and the affected vascular and lymphatic tissue regressed. No side effects have been observed. This report underlines the importance of early variant detection in children suspected of having severe mosaic overgrowth, and proves that prenatal diagnosis is possible, enabling prompt treatment. Furthermore, it demonstrates the promising effects of alpelisib in this patient group.
AB - Mosaic PIK3R1 variants have recently been demonstrated in patients with complex vascular malformations and overgrowth in a syndrome resembling PIK3CA-related overgrowth syndrome (PROS). The PIK3CA-inhibitor, alpelisib, seems to be a promising treatment option for PROS patients. We describe a young boy with overgrowth and a pathogenic mosaic variant in PIK3R1; c.1699A > G, p.(Lys567Glu). He was prenatally suspected of a syndrome on the presence of unusual transient fluctuating subcutaneous edemas and lymphedema of his left shoulder. The pathogenic variant, later found to be causative, was below detection threshold in whole-genome sequencing (WGS) analysis of amniotic fluid. Upon delivery a mosaic pathogenic PIK3R1 variant, was identified by whole-exome sequencing (WES) of a skin biopsy. With no proven treatment options available, and based on the theoretical disease mechanism, alpelisib therapy was initiated at nine months of age. In the first year of treatment growth normalized and the affected vascular and lymphatic tissue regressed. No side effects have been observed. This report underlines the importance of early variant detection in children suspected of having severe mosaic overgrowth, and proves that prenatal diagnosis is possible, enabling prompt treatment. Furthermore, it demonstrates the promising effects of alpelisib in this patient group.
KW - Alpelisib
KW - Congenital vascular malformation
KW - Mosaicism
KW - Personalized medicine
KW - PIK3R1
KW - Segmental overgrowth
U2 - 10.1016/j.ejmg.2022.104590
DO - 10.1016/j.ejmg.2022.104590
M3 - Journal article
C2 - 35964931
AN - SCOPUS:85135887947
VL - 65
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
SN - 1769-7212
IS - 10
M1 - 104590
ER -
ID: 319806703