SAM syndrome is characterized by extensive phenotypic heterogeneity

Area of Science:

• Genetics and Molecular Biology
• Dermatology
• Rare Genetic Diseases

Background:

• Severe skin dermatitis, multiple allergies and metabolic wasting (SAM) syndrome is a rare, life-threatening inherited disorder.
• It is caused by bi-allelic mutations in the DSG1 gene, which encodes desmoglein 1.
• Initial reports described severe erythroderma, failure to thrive, atopic manifestations, recurrent infections, hypotrichosis, and palmoplantar keratoderma.

Observation:

• Three new cases of SAM syndrome across two families were analyzed.
• Genetic analysis, including whole exome and direct sequencing, identified homozygous mutations in DSG1.
• These mutations were predicted to cause premature termination of translation.

Findings:

• All analyzed patients with SAM syndrome had homozygous mutations in DSG1.
• The clinical presentations in these new cases showed a wide spectrum of severity, differing from previously reported patients.
• This highlights extensive phenotypic heterogeneity in SAM syndrome.

Implications:

• The findings underscore the significant variability in clinical manifestations of SAM syndrome.
• This phenotypic heterogeneity suggests the influence of potent modifier genes or other genetic factors.
• Further research into these modifiers is crucial for understanding disease progression and developing targeted therapies.