Early diagnosis enabling precision medicine treatment in a young boy with PIK3R1-related overgrowth.
Eur J Med Genet
; 65(10): 104590, 2022 Oct.
Article
in En
| MEDLINE
| ID: mdl-35964931
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vascular Malformations
/
Musculoskeletal Abnormalities
Type of study:
Diagnostic_studies
/
Prognostic_studies
/
Screening_studies
Limits:
Child
/
Female
/
Humans
/
Male
/
Pregnancy
Language:
En
Journal:
Eur J Med Genet
Journal subject:
GENETICA MEDICA
Year:
2022
Document type:
Article
Affiliation country:
Denmark
Publication country:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS