BACKGROUND: Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by microcephaly, white matter lesions, numerous intracranial calcifications, chilblain skin lesions and high levels of interferon-α (IFN-α) in the cerebrospinal fluid (CSF). However, ocular involvement is reported significantly less frequently.
METHODS: We present a case of a neonate with hypotrophy, microcephaly, frostbite-like skin lesions, thrombocytopenia, elevated liver enzymes and hepatosplenomegaly. Magnetic resonance imaging (MRI) of the brain showed multiple foci of calcification, white matter changes, cerebral atrophy, and atrophic dilatation of the ventricular system. The inflammatory parameters were not elevated, and the infectious etiology was excluded. Instead, elevated levels of IFN-α in the serum were detected. Based on the related clinical symptoms, imaging and test findings, the diagnosis of AGS was suspected. Genetic testing revealed two pathogenic mutations, c.490C>T and c.222del (novel mutation), in the three prime repair exonuclease 1 (TREX1) gene, confirming AGS type 1 (AGS1). An ophthalmologic examination of the child at 10 months of age revealed an impaired pupillary response to light, a corneal haze with Haab lines in the right eye (RE), pale optic nerve discs and neuropathy in both eyes (OU). The intraocular pressure (IOP) was 51 mmHg in the RE and 49 in the left eye (LE). The flash visual evoked potential (FVEP) showed prolonged P2 latencies of up to 125% in the LE and reduced amplitudes of up to approximately 10% OU. This girl was diagnosed with congenital glaucoma, and it was managed with a trabeculectomy with a basal iridectomy of OU, resulting in a reduction and stabilization in the IOP to 12 mmHg in the RE and 10 mmHg in the LE without any hypotensive eyedrops.
CONCLUSIONS: We present the clinical characteristics, electrophysiological and imaging findings, as well as the genetic test results of a patient with AGS1. Our case contributes to the extended ophthalmic involvement of the pathogenic c.490C>T and c.222del mutations in TREX1.

BACKGROUND: Autoinflammatory diseases (AIDs) constitute several disorders that are characterized by the presence of recurrent episodes of unprovoked inflammation due to dysregulated innate immune system in the absence of autoantibodies or infections. Most of them have a strong genetic background, with mutations in single genes involved in inflammation referred to monogenic AIDs. In this article, we will review the cardiac manifestations in various monogenic AIDs.
METHODS: Various cardiac manifestations can be seen in various monogenic AIDs, including pericarditis, valvular diseases, coronary diseases, cardiomyopathies, and pulmonary hypertension, especially in Familial Mediterranean fever (FMF).
UNASSIGNED: Monogenic AIDs can manifest a variety of cardiac lesions, the most common of which is pericardial effusion, which may be local pericardial inflammation secondary to systemic inflammatory responses. While, the pathogenesis and incidence are still unclear. More research is still needed to explore the relationship between monogenic AIDs and cardiac damage for better understanding these diseases.

Acral necrotic ulcers in infancy are rare but have been described in type I interferonopathies. Herein, we present a case of an 8-year-old child who presented at the age of one month with severe ulceronecrotic lesions on the face and limbs with exacerbations following exposure to cold weather. Despite extensive investigation the case remains undiagnosed to this day. We hypothesize that this case represents a novel and yet unknown autoinflammatory disease.

In this article we revised the literature on Inborn Errors of Immunity (IEI) keeping our focus on those diseases presenting with intrauterine or perinatal clinical manifestations. We opted to describe our findings according to the IEI categories established by the International Union of Immunological Societies, predominantly addressing the immunological features of each condition or group of diseases. The main finding is that such precocious manifestations are largely concentrated in the group of primary immune regulatory disorders (PIRDs) and not in the group of classical immunodeficiencies. The IEI categories with higher number of immunological manifestations in utero or in perinatal period are: (i) diseases of immune dysregulation (HLH, IPEX and other Tregopathies, autosomal recessive ALPS with complete lack of FAS protein expression) and (ii) autoinflammatory diseases (NOMID/CINCA, DIRA and some interferonopathies, such as Aicardi-Goutières syndrome, AGS, and USP18 deficiency). Regarding the other IEI categories, some patients with Omenn syndrome (an atypical form of SCID), and a few X-linked CGD patients present with clinical manifestations at birth associated to immune dysregulation. The most frequent clinical features were hydrops fetalis, intrauterine growth retardation leading to fetal loss, stillbirths, and prematurity, as in HLH and IPEX. Additionally, pseudo-TORCH syndrome was observed in AGS and in USP18 deficiency. The main goal of our review was to contribute to increasing the medical awareness of IEI with intrauterine and perinatal onset, which has obvious implications for diagnosis, treatment, and genetic counseling.

Type 1 diabetes (T1D) has been associated with both genetic and environmental factors. Increasing incidence of T1D worldwide is prompting researchers to adopt different approaches to explain the biology of T1D, beyond the presence and activity of autoreactive lymphocytes. In this review, we propose inflammatory pathways as triggers for T1D. Within the scope of those inflammatory pathways and in understanding the pathogenesis of disease, we suggest that viruses, in particular Coxsackieviruses, act by causing a type 1 interferonopathy within the pancreas and the microenvironment of the islet. As such, this connection and common thread represents an exciting platform for the development of new diagnostic, treatment and/or prevention options.