1 Introduction

Aicardi–Goutières syndrome (AGS) is a rare and complex neuroinflammatory disorder characterized by severe neurological problems, skin manifestations, and potential overlap with autoimmune disorders [1]. Although most individuals with AGS exhibit profound intellectual disability, it is intriguing to encounter exceptional abilities amidst such challenges [2, 3]. In this case report, we present a remarkable and rare instance of AGS, where our patient demonstrates an extraordinary talent in painting and visualizing objects with extraordinary precision and attention to detail (Figure 1). AGS is typically associated with a progressive and debilitating course, leading to significant neurodevelopmental regression and lifelong disabilities [3]. Common clinical features include intermittent fever, skin manifestations such as chilblains and ulcers, muscular abnormalities, and elevated levels of interferon-alpha in the cerebrospinal fluid [1, 4]. However, the presence of exceptional talents within the context of AGS presents a unique opportunity to explore the multifaceted nature of cognitive abilities in this syndrome [3]. This case report aims to shed light on the clinical manifestations of AGS while emphasizing the exceptional artistic talent observed in our patient. By documenting and sharing this remarkable ability, we seek to contribute to a deeper understanding of the cognitive heterogeneity within AGS and inspire further research in this domain. Furthermore, this case underscores the importance of considering AGS in individuals presenting with the described clinical features and highlights the need for comprehensive evaluation, multidisciplinary approaches, and ongoing research to optimize management and support for affected individuals. This report serves as a reminder of the potential for hidden talents and strengths, even in the face of significant neurological challenges, and underscores the importance of embracing the unique abilities of individuals with AGS for a more comprehensive understanding of this rare syndrome.

2 Case Report

2.1 Case History and Examination

The male child was born in 2012 from a consanguineous marriage via caesarean section at term, with a birth weight of 3150 g. His current weight is 25 kg, and his height is 123 cm. At birth, his head circumference was 35 cm, which increased to the 50th percentile during the first 6 months (39.5 cm at 3 months and 40.5 cm at 4 months). The child exhibited delayed developmental milestones, including delays in walking and speech, necessitating assistance and occupational therapy for independent mobility by 1 year of age. Additionally, no family members have demonstrated any inflammatory phenotype, and no positive points in the family history regarding similar conditions. The initial presenting symptom at birth was abnormal eye movements and strabismus, which required surgical intervention on both eyes at 4 years of age. At 3 months old, the patient experienced encephalopathy following treatment with ketotifen, with a possibility of an allergic cough as the underlying cause, resulting in a 20-day period of decreased consciousness. This was accompanied by muscle weakness and hypotonia, further complicating his clinical picture. Around 8 months of age, generalized skin lesions began to appear, initially presenting as vesicular and pustular eruptions predominantly affecting the palms and soles. Over time, these skin lesions progressed to involve the entire body (Figure 2).

3 Discussion

The case we presented involves a pathogenic variant in the TREX1 gene, which is associated with Aicardi–Goutières syndrome 1 (AGS1). Mutations in TREX1 gene are present in approximately 22% of patients [2]. AGS is a rare neuroinflammatory disorder characterized by severe neurological problems, skin lesions, and elevated levels of interferon-alpha in the cerebrospinal fluid [4, 5]. The prevalence of AGS is estimated at more than 4000 worldwide [2]. The neurological damage caused by AGS often leads to profound intellectual disability, spasticity, dystonia, and hypotonia [2]. The clinical features of AGS that we described in our case aligns with these features, such as skin lesions, oral ulcers, muscle abnormalities, spasticity, dystonia and also hypotonia. AGS is known to have a progressive and debilitating nature, with many affected individuals not surviving past childhood [6]. However, it is important to note that some individuals with milder neurological problems or later-onset AGS can live into adulthood [3, 6]. Mortality in childhood ranges from 13% to 35% [6]. Our patient's case deviates from the typical presentation of AGS. Unlike most AGS patients, this individual exhibited fewer neurological symptoms and less severe neurodevelopmental impairments. Instead, our patient presented with prominent symptoms of immunodeficiency and exacerbated immune responses. Genetic analysis revealed a specific gene mutation as the underlying cause, contributing to this distinct clinical presentation. We should mention that some individuals with AGS exhibit features similar to autoimmune disorders, including systemic lupus erythematosus (SLE) [4]. This overlap in symptoms suggests that there may be shared underlying mechanisms between AGS and autoimmune disorders [4, 6]. One specific feature mentioned is the presence of chilblains, which are painful, itchy skin lesions that occur due to inflammation of small blood vessels. Chilblains can be seen in both AGS and SLE [4, 6]. It should be noted that our patient was evaluated for SLE and the results were negative. The encephalopathic phase of AGS causes severe and permanent neurological damage, often resulting in leukodystrophy, which is the loss of white matter in the brain [3]. The presence of calcium deposits (calcifications) in the brain is another characteristic finding in AGS [6]. These neurological abnormalities contribute to the profound intellectual disability, muscle stiffness (spasticity), involuntary muscle contractions (dystonia), and weak muscle tone (hypotonia) observed in individuals with AGS [1, 6]; as in our patient, there were features such as spasticity, dystonia, hypotonia, though no any leukodystrophy and classification due to normal brain MRI. That is indeed a remarkable and interesting observation about our patient. While most individuals with Aicardi–Goutières Syndrome (AGS) experience profound intellectual disability, the manifestation and severity of cognitive abilities can vary significantly among affected individuals [2, 3]. In some cases, individuals with AGS exhibit specific talents or strengths in certain domains despite their broader cognitive impairments [5]. These exceptional abilities, often termed “islands of skills” or “splinter skills,” have been documented in the, literature [5, 7]. Our patient's remarkable artistic talent—characterized by an ability to paint and visualize objects with striking precision and attention to detail—may represent one such example. Although this talent is not a direct consequence of the TREX1 gene mutation, it could be associated with the preservation or enhancement of specific cognitive functions in brain regions unaffected by the mutation's pathology [5]. The medical literature has noted the presence of unique talents in individuals with intellectual disabilities, including those with AGS, though the mechanisms underlying these “splinter skills” remain incompletely understood [5]. We propose that our patient's artistic abilities may reflect the complex interplay between the TREX1 mutation's impact on certain neural circuits and the intact functioning of other brain areas, such as those involved in visual–spatial processing. This highlights the brain's remarkable plasticity and its capacity to support diverse cognitive profiles, even in the context of a severe neurological disorder like AGS [5]. The variability in cognitive outcomes underscores the need for further research into how genetic mutations influence both deficits and strengths. Given this, our patient's talent offers a unique opportunity for clinical and therapeutic exploration. Encouraging these artistic abilities through art therapy or structured engagement in art programs could provide a meaningful outlet for self-expression and communication, potentially enhancing their quality of life. Such interventions may foster personal growth and fulfillment, leveraging a strength that stands out amidst the challenges posed by AGS. Overall, our patient's exceptional capacity for painting and visualizing objects with precision and detail is a rare and noteworthy feature. It not only enriches our understanding of the phenotypic variability in AGS but also emphasizes the potential for preserved brain function to support extraordinary abilities in the presence of a TREX1 mutation. It presents an opportunity for further exploration and support to enhance their artistic skills and overall well-being. During the encephalopathic phase of AGS, affected individuals experience regression in their developmental skills, growth retardation of the brain and skull (microcephaly), and may exhibit intermittent fevers without infection (sterile pyrexias) and seizures [3]. In most cases, patients with Aicardi–Goutières syndrome (AGS) present with severe acquired microcephaly. However, in children with preserved intellect, the head circumference remains within the normal range [3]. In the study conducted by Georgia Ramantani et al., epilepsy was identified as a defining feature of Aicardi–Goutières syndrome (AGS) and was found to typically manifest within the first year of life. The onset of epilepsy is considered a significant milestone in the disease progression and necessitates timely therapeutic intervention [3]. However, it is important to note that in our presented case, the patient did not exhibit any seizures, and was also normocephalic; deviating from the typical pattern observed in AGS. Abnormal findings, such as inflammation-related immune system molecules, can be detected in the cerebrospinal fluid during this phase [8]. These observations support the inflammatory nature of AGS and the impact it has on the central nervous system. In some cases, newborns with AGS may present with features that mimic congenital infections, such as hepatosplenomegaly, elevated liver enzymes, thrombocytopenia, and neurological abnormalities. However, despite the similarities to congenital infection, no actual infection is found in these infants [6, 9]. This highlights the complex nature of AGS and the challenges in diagnosing the condition accurately.

In summary, our presented case demonstrates the key clinical features of Aicardi–Goutières syndrome (AGS), including intermittent fever, skin manifestations such as chilblains and ulcers, and muscular abnormalities. The presence of immunodeficiency and heightened immune responses in our patient, along with milder neurological symptoms, highlights the variability within AGS due to specific gene mutations. Documenting and sharing our patient's exceptional talent can contribute to a better understanding of the cognitive diversity within AGS and stimulate further research. Considering AGS in the differential diagnosis for individuals displaying these clinical features is crucial to ensure appropriate management and support for affected individuals.

4 Conclusion

This case serves as a reminder of the heterogeneity within AGS and the importance of considering this syndrome in the differential diagnosis of individuals presenting with the described clinical features. Accurate diagnosis is crucial for appropriate management and support, including targeted interventions and enhancing overall quality of life. Additionally, documenting our patient's unique artistic talent contributes to understanding the cognitive abilities within AGS. Comprehensive evaluations, ongoing research, and multidisciplinary approaches are vital in managing AGS. Understanding the genetic basis of AGS is crucial for accurate diagnosis and personalized management. Further research is needed to unravel the underlying mechanisms and improve support for individuals with AGS.

Author Contributions

Pooneh Tabibi: conceptualization, data curation, writing – original draft. Reza Shiari: project administration, supervision. Samin Sharafian: resources, supervision, validation. Sara Shiari: data curation, investigation, writing – review and editing.

Consent

Written informed consent was obtained and signed from the patient's parents regarding the use of the patient's health information for the purpose of writing and publishing a case report.

Conflicts of Interest

The authors declare no conflicts of interest.