A young man with scleroderma like skin, chronic non-healing ulcers, and chronic osteomyelitis (for the past 12 years) has been admitted in our ward.
The patient has a strong family history of similar illness with the disease affecting his brothers only.
The disease starts manifesting after the age of 10 and progress over time.
One of the siblings died of unknown reason at the age of 30.
The patient has been investigated at local hospitals but has not been diagnosed yet.
All his autoimmune workup is negative.
The following are potential differential diagnoses:
Key Features:
Progressive bone resorption (acroosteolysis), scleroderma-like skin changes, osteomyelitis, and poor wound healing.
Genetic Basis:
Mutations in the NOTCH2 gene.
Other Symptoms:
Short stature, joint hypermobility, craniofacial abnormalities, and dental issues.
Key Features:
Red scaly patches with keratoderma and scleroderma-like skin changes.
Genetic Basis:
Autosomal dominant form linked to CARD14 mutations.
Other Symptoms:
Follicular hyperkeratosis, erythema, and palmoplantar keratoderma.
Key Features:
Premature aging, scleroderma-like skin changes, chronic ulcers, and osteomyelitis.
Genetic Basis:
Mutations in the WRN gene in Werner syndrome, which causes genomic instability.
Other Symptoms:
Short stature, cataracts, and an increased risk of malignancies.
Key Features:
Progressive osteolysis, nodulosis, joint contractures, and scleroderma-like skin changes.
Genetic Basis:
Mutations in the MMP2 gene.
Other Symptoms:
Joint pain, nodules, and progressive bone loss.
Key Features:
Thickening of the skin (pachyderma), periostosis of long bones, and digital clubbing.
Genetic Basis:
Mutations in HPGD or SLCO2A1 genes.
Other Symptoms:
Coarse facial features, joint pain, and hyperhidrosis.
Key Features:
Chronic recurrent multifocal osteomyelitis (CRMO), congenital dyserythropoietic anemia, and neutrophilic dermatosis.
Genetic Basis:
Mutations in LPIN2 gene.
Other Symptoms:
Recurrent fevers, anemia, and hepatosplenomegaly.
Key Features:
Progressive ossification of soft tissues, scleroderma-like skin changes, and chronic ulceration.
Genetic Basis: Mutations in the ACVR1 gene.
Other Symptoms:
Malformed big toes, restricted joint mobility, and pain.
Key Features:
Thin, translucent skin with a scleroderma-like appearance, chronic ulcers, and osteomyelitis.
Genetic Basis:
Mutations in the COL3A1 gene.
Other Symptoms:
Easy bruising, arterial rupture, and gastrointestinal perforations.
Given the familial occurrence and the severe, progressive nature of the condition, genetic testing is highly recommended to identify the underlying mutation. A thorough family history and potentially involving a geneticist could provide further clarity.
Further diagnostic workup could include skin biopsy, bone imaging (X-rays or MRI), and possibly next-generation sequencing to identify the genetic mutation responsible for the condition.