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

Svetlana Vakkilainen (1) , Laura Puhakka (1) , Paula Klemetti (1) , Kaarina Heiskanen (1) , Mikko Seppänen (1) , Mikko Muona (2) , Céline Posseme (3) , Darragh Duffy (4) , Timo Vaisanen (1) , Outi Elomaa (1, 5) , Maarit Palomäki (1) , Harri Saxén (1) , Annamari Ranki (1) , Katariina Hannula-Jouppi (1, 5)

1 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
2 Blueprint Genetics
3 CRT - Centre de Recherche Translationnelle - Center for Translational Science
4 Immunobiologie des Cellules Dendritiques
5 Folkhälsan Research Center

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.

Mots clés: SAM syndrome; desmoplakin; severe dermatitis; metabolic wasting; desmoglein

Domaines: Immunologie

Svetlana Vakkilainen, Laura Puhakka, Paula Klemetti, Kaarina Heiskanen, Mikko Seppänen, et al.. Novel DSP Spectrin 6 Region Variant Causes Neonatal Erythroderma, Failure to Thrive, Severe Herpes Simplex Infections and Brain Lesions. Acta Dermato-Venereologica, 2019, ⟨10.2340/00015555-3203⟩. ⟨pasteur-02173489⟩