Dermatologic
for epidermolysis bullosa, genodermatoses, and mosaic skin disorders with genome sequencing and RNA-seq
System Profile
Yield Comparison
Clinical Dimensions
- Cafe-au-lait spots
- Ash-leaf macules
- Hemangiomas
- Unusual or keloid scarring
- Streaky pigmentation
- Alopecia
- Neurofibromatosis type 1
- Legius
- Tuberous sclerosis complex
- Incontinentia pigmenti
- Ectodermal dysplasias
- Oculocutaneous albinism
- Cafe-au-lait patches
- Hypopigmented macules
- Vascular lesions
- Shagreen patches
- Angiofibromas
- Linear epidermal nevi
- Hyperextensible or fragile skin
- Unusual scars
- Alopecia patches
- Recurrent rashes
- Pigment changes
- Easy bruising
- Skin fragility
- Severe eczema
- Pruritus without clear allergy
- Recurrent skin infections
- Elevated tryptase
- Eosinophilia
- Abnormal immunoglobulins
- Biopsy-based abnormalities
- High IgE in Hyper-IgE syndrome
- Neurocutaneous imaging with cortical tubers
- Subependymal nodules
- Meningiomas
- Vascular malformations
- Skin ultrasound for deep vascular lesions
- Skin biopsy showing ectodermal dysplasia, mosaic pigment, collagen defects
- Wood's lamp showing pigmentary mosaicism or hypopigmented macules
- Multiple topical/systemic dermatologic agents
- Immunomodulators for severe eczema or genodermatoses
- Repeated laser treatments for lesions
- Severe eczema or urticaria with minor exposures
- Drug rashes
- Blistering disorders after low-dose meds
- Angioedema
- Excision of multiple neurofibromas
- Large hemangiomas
- Skin tumors associated with syndromes
- Biopsies confirming genodermatoses
- Dermatology-directed regimens for chronic genetic skin conditions
- Scar management
- Chronic wound care
- Compression garments
- Protective dressings for fragile skin
- UV-protective gear in albinism
- Dermatology or neurocutaneous clinic following
- Combined derm-genetics visits
- Dermatologist suspecting NF/TSC or mosaicism
- Cafe-au-lait spots
- Hypopigmented lesions
- Neurocutaneous disorders (NF/TSC/IP)
- Albinism
- Chronic eczema/skin fragility running in family
- No significant sun exposure or irritant contact to explain pigment changes or scarring
- Rashes and lesions present since infancy
- Birthmarks (cafe-au-lait, ash-leaf)
- Linear pigmentation
- Large hemangiomas
- Ichthyosis
- Congenital alopecia or skin fragility
Red Flag Combinations
Clinical patterns that should prompt consideration of genetic testing
Cafe-au-lait spots + learning difficulties
Ash-leaf macules + seizures
Linear pigmentation + developmental delay
Skin fragility + joint hypermobility
Screening Decision Pathway
When to consider genetic testing for dermatologic presentations
graph TD
START["Patient Presents with\nDermatologic Concerns"] --> SCREEN{"Screen for\nRed Flags"}
SCREEN --> RF1["Newborn exam documenting pigmentary anomalies"]
SCREEN --> RF2["School skin checks noting unusual lesions"]
SCREEN --> RF3["Photosensitivity noted on routine exam"]
RF1 --> EVAL{"Multiple\nFlags Present?"}
RF2 --> EVAL{"Multiple\nFlags Present?"}
RF3 --> 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\n58-95% 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 exam documenting pigmentary anomalies
- School skin checks noting unusual lesions
- Photosensitivity noted on routine exam
Exome / Genome Sequencing Indications
Clinical scenarios supporting ES/GS as a diagnostic approach
- Neurocutaneous findings (NF-like, TSC-like, pigment mosaicism) plus neurological or systemic features
- Multiple unexplained lesions
- Strong family history of similar findings
Key Evidence
Published studies supporting genetic testing for dermatologic conditions
| Study | Year | Type | Sample | Yield | Key Finding |
|---|---|---|---|---|---|
| Diagnostic Yield of Next-Generation Sequencing Applied to Ne... | 2018 | Cohort | None | 36.5% | RASopathies NGS panel with functional analysis improved diagnostic yield from 31... |
| Diagnostic Utility of Next-Generation Sequencing for Disorde... | 2019 | Cohort | None | 58% | 58% diagnostic yield in 343 individuals with mosaic skin disorders; variants det... |
| Whole-Transcriptome Analysis by RNA Sequencing for Genetic D... | 2021 | Cohort | None | 88% | 88% diagnostic yield with RNA sequencing in 40 families with inherited skin diso... |
| Whole Exome Sequencing for Ehlers-Danlos Syndrome Differenti... | 2022 | Cohort | None | None | WES enables molecular subtyping and differential diagnosis in clinically overlap... |
| NOD2 Sequencing Identifies Blau Syndrome Among Patients With... | 2024 | Cohort | None | 21.1% | NOD2 targeted sequencing identified Blau syndrome in 21.1% of patients initially... |
| PIK3CA-Related Overgrowth Spectrum: Deep Sequencing for Soma... | 2023 | Cohort | None | None | Deep sequencing detects somatic mosaicism in PIK3CA-related overgrowth spectrum ... |
| Evolution of Genome Diagnostics in Epidermolysis Bullosa: Un... | 2024 | Cohort | None | 94-95% | 94-95% diagnostic yield in 308 epidermolysis bullosa cases with NGS panel (COL7A... |
| KLK15 Variants in Hypermobile Ehlers-Danlos Syndrome | 2024 | Cohort | None | None | KLK15 gene variants identified as potential molecular basis for hypermobile EDS |
Updated: 2026-02-25
Curated by: human
Status: human reviewed