IllnessWiskott-Aldrich syndrome, differential diagnosis

NGS +

[Sanger]

Wiskott-Aldrich syndrome is characterized by immunodeficiency, eczema and coagulation disorders (microthrombocytopenia). There is an increased risk of various immune and inflammatory diseases, increased susceptibility to infections by bacteria, viruses and fungi. In addition, autoimmune phenomena are observed and, if adulthood is reached, certain malignancies such as lymphomas. The syndrome belongs to a spectrum from X-linked thrombocytopenia to severe congenital neutropenia, caused by different mutations in the WAS gene. Wiskott-Aldrich Syndrome is X-linked inherited with complete penetrance in males, female carriers are usually symptom-free - except e.g. in case of shifted X chromosome inactivation. In the WAS gene, 95% of mutations are detected by DNA sequencing, the rest by deletion/duplication analysis. The diagnostic yield in differential diagnostics depends on the clinical findings. An inconspicuous genetic finding therefore does not mean that the clinically suspected diagnosis can be excluded with certainty.

(Basic diagnostic genes: ###; additional genes: ###)

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1178/

• Alias: Eczema-thrombocytopenia-immunodeficiency syndrome
• Alias: Immundefekt kombiniert mit Thrombozytopenie und Ekzem
• Allelic: Adenosine deaminase deficiency, partial (ADA)
• Allelic: Anauxetic dysplasia 1 (RMRP)
• Allelic: Anemia, XL, with/without neutropenia and/or platelet abnormalities (GATA1)
• Allelic: Autoimmune disease, multisystem, infantile-onset, 1 (STAT3)
• Allelic: Dursun syndrome (G6PC3)
• Allelic: Leukemia, megakaryoblastic, with/-out Down syndrome, somatic (GATA1)
• Allelic: Myelokathexis, isolated (CXCR4)
• Allelic: Neutropenia, nonimmune chronic idiopathic, of adults (GFI1)
• Allelic: Neutrophilia, hereditary (CSF3R)
• Allelic: Omenn syndrome (RAG1, RAG2)
• Allelic: Thrombocytopenia with beta-thalassemia, XL (GATA1)
• Allelic: Thrombocytopenia, XL, with/-out dyserythropoietic anemia (GATA1)
• Combined cellular + humoral immune defects with granulomas (RAG1, RAG2)
• Combined immunodeficiency, XL, moderate (IL2RG)
• Diamond-Blackfan anemia 14 with mandibulofacial dysostosis (TSR2)
• Hermansky-Pudlak syndrome 2 (AP3B1)
• Hyper-IgE recurrent infection syndrome (STAT3)
• Hyper-IgE recurrent infection syndrome, AR (DOCK8)
• Immunodeficiency 71 with inflammatory disease + congenital thrombocytopenia (ARPC1B)
• Immunodeficiency, XL with hyper-IgM (CD40LG)
• Immunodysregulation, polyendocrinopathy + enteropathy XL, IPEX (FOXP3)
• Netherton syndrome [cong. erythroderma, hair-shaft abnormality, atopy + high IgE] (SPINK5)
• Neutropenia, cyclic (ELANE)
• Neutropenia, severe congenital 1, AD (ELANE)
• Neutropenia, severe congenital 2, AD (GFI1)
• Neutropenia, severe congenital 3, AR (HAX1)
• Neutropenia, severe congenital 4, AR (G6PC3)
• Neutropenia, severe congenital, 7, AR (CSF3R)
• Neutropenia, severe congenital, XL (WAS)
• Periodic fever, immunodeficiency + thrombocytopenia syndrome (WDR1)
• Severe combined immunodeficiency due to ADA deficiency (ADA)
• Severe combined immunodeficiency, B cell-negative (RAG1, RAG2)
• Severe combined immunodeficiency, T-cell negative, B-cell/natural killer cell-positive type (IL7R)
• Severe combined immunodeficiency, XL (IL2RG)
• Thrombocytopenia, XL (WAS)
• Thrombocytopenia, XL, intermittent (WAS)
• WHIM syndrome 1 (CXCR4)
• Wiskott-Aldrich syndrome (WAS)
• Wiskott-Aldrich syndrome 2 (WIPF1)