Hematologic/Lymphatic
for lymphatic malformations and hereditary lymphedema with exome/genome sequencing
System Profile
Yield Comparison
Clinical Dimensions
- Recurrent infections
- Chronic lymphadenopathy
- Cytopenias
- Bleeding issues
- Failure to thrive with infections
- SCID
- Chronic granulomatous disease
- Wiskott-Aldrich
- HLH
- Periodic fever syndromes
- Congenital neutropenias
- Pallor
- Petechiae
- Easy bruising
- Lymphadenopathy
- Hepatosplenomegaly
- Chronic eczema
- Mucosal bleeding
- Recurrent oral ulcers
- Frequent infections
- Easy bruising
- Recurrent nosebleeds
- Prolonged fevers
- Chronic fatigue after mild infections
- Pancytopenia
- Neutropenia
- Lymphopenia
- Thrombocytopenia
- Abnormal immunoglobulins
- Very high ferritin
- Elevated soluble IL-2 receptor
- Inflammatory markers without infection
- CT/MRI showing persistent lymphadenopathy
- Splenomegaly
- Marrow infiltration
- Thymic hypoplasia
- Organomegaly with cytopenias
- Flow cytometry showing T/B/NK cell deficits
- Bone marrow biopsy with HLH features
- Immunoglobulin panels abnormal
- Neutrophil oxidative burst test abnormal (CGD)
- Chronic antibiotics
- IVIG or SCIG
- Long-term steroids or immunosuppressants for cytopenias or HLH
- Frequent transfusions
- Severe drug reactions causing marrow suppression or cytopenias
- Recurrent DRESS or SJS/TEN in context of genetic predisposition
- Splenectomy
- Lymph node biopsies
- Port placement for chronic transfusions or chemo
- Thymectomy
- Education and support for chronic infections
- Transfusion planning
- Immune monitoring
- Port-a-cath for transfusions
- Splenectomy prophylaxis tools
- Home infusion equipment
- Hematology/oncology for cytopenias, immune cytopenias, HLH
- Lymphoproliferative disease clinics
- Heme expressing concern for inherited immune/bleeding disorder
- Cytopenias
- Early leukemias/lymphomas
- Recurrent fevers
- Periodic fever syndromes
- Autoimmune cytopenias in family
- No crowding, daycare, or obvious exposure explaining recurrent infections
- Siblings also affected
- Infections occur despite good care and nutrition
- Recurrent early infections
- Omphalitis
- Neonatal sepsis
- Lymphadenopathy or splenomegaly
- Unexplained cytopenias in newborn period
Red Flag Combinations
Clinical patterns that should prompt consideration of genetic testing
Recurrent infections + eczema + thrombocytopenia
Cytopenias + hepatosplenomegaly + fevers
Periodic fevers + serositis
Recurrent infections + failure to thrive
Screening Decision Pathway
When to consider genetic testing for hematologic/lymphatic presentations
graph TD
START["Patient Presents with\nHematologic/Lymphatic Concerns"] --> SCREEN{"Screen for\nRed Flags"}
SCREEN --> RF1["Newborn CBC or infection screens with cytopenias"]
SCREEN --> RF2["PCP infection-risk tools flagging recurrent severe..."]
RF1 --> EVAL{"Multiple\nFlags Present?"}
RF2 --> EVAL{"Multiple\nFlags Present?"}
EVAL -->|Yes| TEST["Order Genetic Testing\n(ES/GS)"]
EVAL -->|No| MONITOR["Continue Monitoring\nRe-evaluate if New Findings"]
TEST --> DX["Molecular Diagnosis\n15-79% yield"]
style TEST fill:#dcfce7,stroke:#16a34a,color:#14532d
style DX fill:#bbf7d0,stroke:#16a34a,color:#14532d
style MONITOR fill:#fef3c7,stroke:#d97706,color:#92400e
Screening Red Flags
Findings on routine screening that may indicate genetic etiology
- Newborn CBC or infection screens with cytopenias
- PCP infection-risk tools flagging recurrent severe infections
Exome / Genome Sequencing Indications
Clinical scenarios supporting ES/GS as a diagnostic approach
- Recurrent or severe infections
- Cytopenias
- HLH
- Immune dysregulation without clear cause
- Negative first-line PIDD panel
- Strong family clustering
Key Evidence
Published studies supporting genetic testing for hematologic/lymphatic conditions
| Study | Year | Type | Sample | Yield | Key Finding |
|---|---|---|---|---|---|
| PIK3CA-related overgrowth spectrum: review of vascular manif... | 2021 | Review | None | None | Comprehensive review of PIK3CA-related overgrowth spectrum with focus on vascula... |
| cfDNA NGS liquid biopsy for AVM molecular diagnosis | 2020 | Cohort | 5 | None | Cell-free DNA NGS liquid biopsy detects somatic variants in arteriovenous malfor... |
| cfDNA NGS for Maffucci syndrome | 2022 | Case Report | 1 | None | Cell-free DNA next-generation sequencing successfully detects IDH1 somatic varia... |
| Clinical and molecular spectrum of sporadic venous malformat... | 2022 | Cohort | 43 | None | Molecular characterization of sporadic venous malformations identifies TEK/TIE2 ... |
| Genetic causes of vascular malformations | 2022 | Review | None | None | Comprehensive review of genetic causes of vascular malformations across PI3K/AKT... |
| RAS pathway variants in disorders of somatic mosaicism | 2022 | Cohort | 938 | None | RAS pathway somatic variants characterized in 938 patients with disorders of som... |
| NGS panel for AVM evaluation | 2023 | Cohort | 54 | 68.5% | 68.5% somatic variant detection using targeted NGS panel for arteriovenous malfo... |
| HHT somatic second-hit mutations in telangiectasia and AVM | 2024 | Cohort | 14 | None | Somatic second-hit mutations identified in HHT lesional tissue supporting two-hi... |
Updated: 2026-02-25
Curated by: human
Status: human reviewed