Juvenile Dermatomyositis and Infantile Cerebral Palsy: Aicardi-Gouteres Syndrome, Type 5, with a Novel Mutation in SAMHD1-A Case Report

• Published in: Biomedicines Vol. 11; no. 6; p. 1693
• Main Authors: Sorokina, Lubov S, Raupov, Rinat K, Kostik, Mikhail M
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-06-2023; MDPI
• Subjects: Age; Aicardi-Gouteres syndrome; Amino acid substitution; Arthritis; Basal ganglia; Calcification; Case Report; Case reports; Cerebellum; Cerebral palsy; CNS calcifications; Convulsions & seizures; Corpus callosum; Corticosteroids; Cytomegalovirus; Dermatomyositis; Disease; Edema; Encephalopathy; Erythema; Fever; Genes; Genetic aspects; Genetic counseling; Genomes; Glaucoma; Health aspects; Hypoplasia; infantile cerebral palsy; Infectious diseases; Interferon; interferonopathy; Kinases; Leukodystrophy; Magnetic resonance imaging; Medical screening; Methotrexate; Mutation; Myositis; Nervous system; Neurological complications; Paralysis; Patients; Pediatrics; SAMHD1; Seizures; Seizures (Medicine); Skin; Skin diseases; sleukodystrophy; Spasticity; Steroids; Tofacitinib; Toxoplasmosis; infantile cerebral palsy; sleukodystrophy; CNS calcifications; ICP; interferonopathy; Aicardi-Gouteres syndrome; SAMHD1
• ISSN: 2227-9059; 2227-9059
• DOI: 10.3390/biomedicines11061693

Aicardi-Gouteres syndrome (AGS) is a monogenic interferonopathy characterized by early onset, dysregulation of skin (chilblain lesions), brain, and immune systems (fever, hepatomegaly, glaucoma, arthritis, myositis, and autoimmune activity). The disease looks like TORCH (Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes) infection with early-onset encephalopathy resulting in severe neuropsychological disability.
A six-year-old girl has been suffering from generalized seizures, fever episodes, severe psychomotor development delay, and spastic tetraparesis since the first year of her life. Her two elder brothers died at a young age from suspected infantile cerebral palsy (ICP). Other siblings (younger brother and two elder sisters) are as healthy as their parents. The girl was diagnosed with juvenile dermatomyositis at 5.5 years. Basal ganglia, periventricular, and cerebellum calcifications; hypoplasia of the corpus callosum; and leukodystrophy were detected on CT. The IFN-I score was 12 times higher than normal. The previously not described nucleotide variant c.434G > C (chr 20:36935104C > G; NM_015474) was detected in exon 4 of the SAMHD1 gene in the homozygous state, leading to amino acid substitution p.R145P. Aicardi-Goutières syndrome 5 was diagnosed. Her treatment included corticosteroids, methotrexate, and tofacitinib 5 mg twice a day and it contributed to health improvements. The following brain CT depicted the previously discovered changes without the sign of calcification spreading.
Early diagnosis of AGS is highly important as it allows starting treatment in a timely manner. Timely treatment, in return, can help avoid the development/progression of end-organ damage, including severe neurological complications and early death. It is necessary to spread information about AGS among neurologists, neonatologists, infectious disease specialists, and pediatricians. A multidisciplinary team approach is required.