Akademik Veri Yönetim Sistemi
17th Annual ICORD Meeting, İzmir, Türkiye, 14 - 16 Kasım 2025, ss.1, (Özet Bildiri)
Photodermatoses represent a heterogeneous group of disorders characterized by abnormal cutaneous responses to ultraviolet radiation. While common forms such as polymorphic light eruption or chronic actinic dermatitis typically involve only the skin, syndromic variants may also present with ocular and neurodevelopmental manifestations. Despite major advances in genomic testing, the etiology remains undefined in some patients, underscoring the complexity of genotype–phenotype correlations. This report presents members of the same family with multisystem involvement in whom a definitive diagnosis could not be established despite comprehensive investigations.
A 26-year-old male was evaluated for recurrent skin lesions triggered by sun exposure since the age of two. The lesions, confined to sun-exposed areas, were characterized by erythematous, burn-like patches with crusting and variable healing stages. Ophthalmologic examination revealed ectropion and pronounced nystagmus, while neurodevelopmental delay was also noted. The family history included two siblings with similar photosensitive lesions and nystagmus, one healthy sister, and unaffected parents.
Whole-exome sequencing revealed no pathogenic variants, identifying only a heterozygous AHR c.544C>T variant classified as a variant of uncertain significance (VUS). Although AHR has been linked to retinitis pigmentosa, this variant did not explain the phenotype. Chromosomal microarray and karyotyping were normal. Brain MRI showed subcortical T2 hyperintense lesions consistent with a metabolic disorder. A preauricular biopsy suspected of squamous cell carcinoma was compatible with atypical fibroxanthoma. Skin biopsies from photosensitive areas revealed hyperkeratosis and acanthosis.
The coexistence of photosensitivity, ocular anomalies, neurodevelopmental delay, and atypical fibroxanthoma suggests a syndromic photodermatosis. DNA repair disorders, particularly xeroderma pigmentosum, were considered but not molecularly confirmed. The association of brain MRI abnormalities with neoplasia further complicates the phenotype. Current diagnostic approaches have limited ability to detect intronic variants, structural rearrangements, mosaicism, or repeat expansions, which may underlie the negative molecular findings.
This case illustrates a photodermatosis with multisystem involvement lacking a definitive molecular diagnosis despite extensive testing. The combination of cutaneous, ocular, and neurological features suggests an unrecognized DNA repair defect or a complex multifactorial phenotype. Advanced analyses such as whole-genome sequencing, long-read sequencing, and transcriptomic profiling may help elucidate the underlying etiology.