Novel DSP Spectrin 6 Region Variant Causes Neonatal Erythroderma, Failure to Thrive, Severe Herpes Simplex Infections and Brain Lesions

• Published in: Acta dermato-venereologica Vol. 99; no. 9; pp. 789 - 796
• Main Authors: Vakkilainen, S, Puhakka, L, Klemetti, P, Heiskanen, K, Seppänen, M, Muona, M, Posseme, C, Duffy, D, Väisänen, T, Elomaa, O, Palomäki, M, Saxén, H, Ranki, A, Hannula-Jouppi, K
• Format: Journal Article
• Language: English
• Published: Sweden Society for Publication of Acta Dermato-Venereologica 01.07.2019; Medical Journals Sweden
• Subjects: Brain Diseases - diagnostic imaging; Brain Diseases - genetics; Child, Preschool; Dermatitis, Exfoliative - diagnosis; Dermatitis, Exfoliative - drug therapy; Dermatitis, Exfoliative - genetics; Dermatologic Agents - therapeutic use; desmoglein; desmoplakin; Desmoplakins - genetics; Failure to Thrive - diagnosis; Failure to Thrive - genetics; Genetic Predisposition to Disease; Genetic Variation; Herpes Simplex - diagnosis; Herpes Simplex - genetics; Herpes Simplex - virology; Humans; Ichthyosis - diagnosis; Ichthyosis - drug therapy; Ichthyosis - genetics; Immunology; Infant; Infant, Newborn; Life Sciences; Male; metabolic wasting; Phenotype; SAM syndrome; severe dermatitis; Severity of Illness Index; Treatment Outcome; Ustekinumab - therapeutic use; desmoplakin; SAM syndrome; metabolic wasting; severe dermatitis; desmoglein
• ISSN: 0001-5555; 1651-2057; 1651-2057
• DOI: 10.2340/00015555-3203

Desmoplakin (DSP) and Desmoglein 1 (DSG1) variants result in skin barrier defects leading to erythroderma, palmoplantar keratoderma and variable [AQ4] other features. Some DSG1 variant carriers present with SAM syndrome (Severe dermatitis, multiple Allergies, Metabolic wasting) and a SAM-like phenotype has been reported in 4 subjects with different heterozygous DSP variants. We report here a patient with a novel DSP spectrin region (SR) 6 variant c.1756C>T, p.(His586Tyr), novel features of brain lesions and severe recurrent mucocutaneous herpes simplex virus infections, with a favourable response to ustekinumab. Through a review of reported cases of heterozygous variants in DSP SR6 (n = 15) and homozygous or compound heterozygous variants in DSG1 (n = 12) and SAM-like phenotype, we highlight phenotypic variability. Woolly hair, nail abnormalities and cardiomyopathy characterize patients with DSP variants, while elevated immunoglobulin E and food allergies are frequent in patients with DSG1 variants. Clinicians should be aware of the diverse manifestations of desmosomopathies.