Germline predisposition to genitourinary rhabdomyosarcoma

Area of Science:

• Pediatric Oncology
• Clinical Genetics
• Cancer Predisposition Syndromes

Background:

• Rhabdomyosarcoma, a rare childhood cancer, can be linked to various genetic conditions.
• Existing literature often lacks detailed sub-classification of rhabdomyosarcoma location and pathology within genetic syndromes.
• This limits understanding of genitourinary-specific associations with genetic predispositions.

Purpose of the Study:

• To review and summarize key genetic syndromes associated with genitourinary rhabdomyosarcoma.
• To highlight the importance of considering germline genetic factors in pediatric genitourinary rhabdomyosarcoma.
• To provide a foundational reference for clinicians evaluating these cases.

Main Methods:

• Literature review and synthesis of existing data on genetic syndromes and genitourinary rhabdomyosarcoma.
• Identification and enumeration of primary differential genetic considerations.
• Discussion of clinical presentation and diagnostic implications.

Main Results:

• Identified primary genetic differential considerations including DICER1 pathogenic variation, Li-Fraumeni syndrome, constitutional mismatch repair deficiency, mosaic variegated aneuploidy, neurofibromatosis type 1, Noonan syndrome, RASopathies, Costello syndrome, and Beckwith-Wiedemann syndrome.
• Noted that genitourinary rhabdomyosarcoma can be the sole presenting sign of an underlying genetic syndrome.
• Emphasized variability in clinical, pathological, and family history features across syndromes.

Conclusions:

• Genetic evaluation, including counseling and testing, is vital for diagnosing underlying tumor predisposition syndromes in children with genitourinary rhabdomyosarcoma.
• Recognizing these germline associations can significantly impact patient management and family counseling.
• This review serves as an introductory guide to germline considerations for genitourinary rhabdomyosarcoma.