Are there genetic predisposition syndromes that relate hearing loss and Burkitt’s lymphoma?

Genetic Predisposition Syndromes Linking Hearing Loss and Burkitt's Lymphoma

There are currently no well-established genetic predisposition syndromes that specifically link hearing loss and Burkitt's lymphoma, but Kabuki syndrome with KMT2D mutations has been documented to present with both conditions.

Genetic Syndromes with Potential Association

Kabuki syndrome is the most notable genetic condition that has been documented to potentially link hearing loss and Burkitt's lymphoma:

• A case report identified a 5-year-old boy with Kabuki syndrome who developed Burkitt lymphoma, with genetic analysis revealing a novel heterozygous mutation in the KMT2D gene 1
• The mutated KMT2D gene may contribute to the development of both conditions, as KMT2D functions as a tumor suppressor gene that is frequently altered in many cancer types 1

Comprehensive Genetic Evaluation Approach

When evaluating a patient with both hearing loss and Burkitt's lymphoma, the American College of Medical Genetics and Genomics (ACMG) recommends:

1. Detailed family history assessment 2:

   • Construct a 3-4 generation pedigree
   • Document consanguinity and paternity
   • Note hearing status of parents and siblings
   • Record ethnicity and country of origin
   • Identify inheritance patterns (AD, AR, X-linked, mitochondrial)
   • Document audiometric characteristics in affected family members

2. Physical examination focused on syndromic features 2:

   • Facial/cervical dysmorphology (synophrys, dystopia canthorum, preauricular pits)
   • Visual anomalies (heterochromia irides, retinitis pigmentosa)
   • Integumentary changes (premature graying, white forelock, abnormal pigmentation)
   • Endocrine abnormalities
   • Cardiac signs or symptoms
   • Renal abnormalities

3. Genetic testing strategy 2:

   • For suspected syndromic causes: gene-specific mutation screening
   • For non-syndromic hearing loss: comprehensive hearing loss gene panel testing
   • If panel testing is negative: consider exome sequencing (ES) or genome sequencing (GS)
   • Include copy number analysis for detecting deletions/duplications

Key Considerations for Genetic Testing

• The ACMG recommends using panels that include genes curated by the Hearing Loss Gene Curation Expert Panel 2
• Pay attention to the performance characteristics of genetic tests, including test design, genomic regions covered, and analytic sensitivity 2
• If genetic testing fails to identify an etiology, the possibility of a genetic cause still remains and should be emphasized to patients 2
• Periodic follow-up care every 3 years with a geneticist is recommended for cases where genetic evaluation failed to identify an underlying cause 2

Multidisciplinary Management

For patients with both hearing loss and Burkitt's lymphoma, a team approach is recommended that includes 2:

• Otolaryngologists
• Clinical geneticists
• Genetic counselors
• Audiologists
• Oncologists
• Other specialists based on additional clinical manifestations

Emerging Research Directions

Research into the genetic basis of both conditions continues to evolve:

• Over 150 genes have been identified in hearing loss 3
• Burkitt lymphoma has been characterized by deregulation of MYC, with additional mutations in genes including ID3, GNA13, RET, and PIK3R1 4
• Further research may uncover additional genetic syndromes that link these conditions

While Kabuki syndrome represents one potential genetic link between hearing loss and Burkitt's lymphoma, patients presenting with both conditions should undergo comprehensive genetic evaluation to identify possible syndromic causes and guide appropriate management.