The importance of chilblains as a diagnostic clue for mild Aicardi-Goutières syndrome.
Aicardi-Goutières syndrome (AGS) is classically characterized by early-onset encephalopathy. However, in some cases, the presenting symptom of concern may actually be cutaneous rather than neurological, leading to the misdiagnosis of the condition. We report the case of three teenage siblings who presented with a lifetime history of chilblain lesions, only one of whom had notable neurologic deficits. Additional findings included acrocyanosis, Raynaud's phenomenon, low-pitch hoarse voice, headache, and arthritis. They were found to have two pathogenic sequence variants in the SAMHD1 gene: a c.602T>A substitution resulting in p.Ile201Asn protein change, previously reported as a pathogenic mutation, as well as a deletion c.719delT which has not been previously reported but results in a predicted pathogenic frame shift mutation. It is important to consider the diagnosis of AGS in patients and families with chilblain lesions in the presence of unexplained neurologic and rheumatic symptoms. © 2016 Wiley Periodicals, Inc.
Department of Dermatology, Oregon Health and Science University, Portland, Oregon.
Kevin
K
Yarbrough
School of Medicine, Oregon Health and Science University, Portland, Oregon.
Calida
C
Danko
Department of Dermatology, Oregon Health and Science University, Portland, Oregon.
Alfons
A
Krol
Department of Molecular and Medical Genetics, Oregon Health and Science University, Portland, Oregon.
Jonathan
J
Zonana
Department of Dermatology, Oregon Health and Science University, Portland, Oregon.
Sabra
S
Leitenberger
D000293:Adolescent; D020274:Autoimmune Diseases of the Nervous System / Q000175:diagnosis* / Q000235:genetics; D001706:Biopsy; D002647:Chilblains / Q000175:diagnosis* / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics; D009154:Mutation; D009421:Nervous System Malformations / Q000175:diagnosis* / Q000235:genetics; D010641:Phenotype; D010808:Physical Examination; D000076106:SAM Domain and HD Domain-Containing Protein 1; D035781:Siblings; D012867:Skin / Q000473:pathology; D014057:Tomography, X-Ray Computed
D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
Aicardi-Goutières syndrome; SAMHD1 protein; autoimmune diseases of the nervous system; chilblains; dermatology; human; skin diseases