DSP – Severe dermatitis, multiple allergies and metabolic wasting syndrome

Heterozygous missense variants in the desmoplakin gene DSP have been implicated in Severe dermatitis, multiple allergies and metabolic wasting syndrome (SAM syndrome). Whole‐exome sequencing of a patient negative for DSG1 mutations identified a de novo DSP c.1757A>C (p.His586Pro) variant in the N‐terminal plakin domain, correlating with classic SAM features including severe dermatitis, multiple allergies, and metabolic wasting in the single proband (PMID:26073755). A review encompassing four additional unrelated subjects with heterozygous DSP spectrin‐repeat 6 variants, such as c.1756C>T (p.His586Tyr), reported a SAM‐like phenotype, underscoring allelic heterogeneity in DSP‐associated barrier defects (PMID:31037311).

Current evidence is limited to isolated case observations without cosegregation data or targeted functional assays for DSP variants in SAM syndrome. Inclusion of DSP in diagnostic panels for SAM syndrome complements DSG1 screening and refines genetic counseling for affected families.

Key Take-home: DSP missense variants in the plakin domain represent a rare but clinically actionable cause of SAM syndrome, warranting broader genetic testing in patients with atopic barrier dysfunction.

References

• The Journal of allergy and clinical immunology • 2015 • Severe dermatitis, multiple allergies, and metabolic wasting syndrome caused by a novel mutation in the N-terminal plakin domain of desmoplakin. PMID:26073755
• Acta dermato-venereologica • 2019 • Novel DSP Spectrin 6 Region Variant Causes Neonatal Erythroderma, Failure to Thrive, Severe Herpes Simplex Infections and Brain Lesions. PMID:31037311

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