In SAM-DSG, the clinical manifestations that were described in the original patient cohort included erythroderma that was present at birth; atopy (including food allergies and high immunoglobulin E [IgE] levels); palmoplantar keratoderma (PPK) with characteristic peripheral yellow papules and plaques on the hands, fingers, and feet; hypotrichosis; recurrent infections; and failure to thrive. Malabsorption, microcephaly, and eosinophilic esophagitis were further features in the original cohort. Subsequently, it was recognized that there is phenotypic heterogeneity with milder, more limited cutaneous presentations in some and milder allergic manifestations in others.
SAM-DSP has a similar clinical presentation; however, severe itch and development of generalized pustulosis are further reported findings.
Pathogenetically, it is postulated that DSG1 mutations give rise to dysfunctional or absent desmoglein with subsequent impairment of desmosome formation in the epidermis. The resulting compromised skin barrier function is thought to contribute to upregulated Th2 immune responses.
PPK is also seen in heterozygote carriers in SAM-DSG kindreds.
Q82.8 – Other specified congenital malformations of skin
774211005 – Severe dermatitis, multiple allergies, metabolic wasting syndrome
Differential Diagnosis & Pitfalls
- Atopic dermatitis
- Omenn syndrome
- Leiner syndrome
- Netherton syndrome
- Job syndrome
- DOCK8 immunodeficiency syndrome
- Nonbullous congenital ichthyosiform erythroderma
- Dilated cardiomyopathy with woolly hair, keratoderma, and tooth agenesis
- Erythrokeratodermia-cardiomyopathy (EKC) syndrome
- Carvajal syndrome