Photosensitivity syndromes

Photosensitivity syndromes are a heterogeneous group of congenital conditions that, from a dermatological perspective, are characterized by a pathologically heightened cutaneous reaction to ultraviolet or visible radiation. They are based on a wide variety of pathogenic mechanisms, such as DNA repair defects or photoreactive metabolites. Typical manifestations include:

• UV- or light-triggered erythema, edema, blisters, or urticarial reactions,
• unusually severe or long-lasting “sunburns,”
• chronic light-induced damage with pigment changes and skin atrophy,
• and, in cases of global DNA repair defects, a significantly increased risk of skin cancer (epithelial and melanocytic tumors).

In the narrower sense of human genetics, photosensitivity syndromes primarily refer to rare inherited disorders with defects in known DNA repair mechanisms such as nucleotide excision repair (NER), double-strand break repair (DSBR), base excision repair (BER), and mismatch repair (MMR). Diseases involving chromosomal instability also belong to this group. 

DNA Repair and Transcription Defects

• Xeroderma pigmentosum: Defect in nucleotide excision repair; marked photosensitivity and a significantly increased risk of skin cancer.
• Cockayne syndrome: Impaired transcription-coupled DNA repair; photosensitivity, growth and neurological developmental disorders, but typically no increased risk of skin cancer.
• COFS syndrome: Cerebro-oculo-facio-skeletal syndrome (a variant of Cockayne syndrome)  
• UV-Sensitive Syndrome: Marked sensitivity to UV radiation and persistent erythema, but no significantly increased risk of skin cancer
• Trichothiodystrophy: Photosensitivity, brittle, low-sulfur hair, ichthyosis, and developmental disorders

Progeroid disorders

• Bloom syndrome
• Progeria in adults (Werner syndrome)
• Infantile progeria (Hutchinson-Gilford syndrome)
• Acrogeria ( metageria)

Genomic instability disorders in which photosensitivity may be part of the complex phenotype.

• Rothmund-Thomson syndrome: Early-onset photosensitive poikiloderma
• Bloom syndrome: Telangiectatic facial erythema following UV exposure
• Kindler syndrome: Early photosensitivity, followed by poikiloderma and skin fragility
• Dyskeratosis congenita: Variable photosensitivity with reticular pigmentation

Metabolic Disorders

• Porphyrias: Light-activated porphyrins generate reactive oxygen species that lead to damage to the affected skin structures (see entry).  

Metabolic and deficiency disorders: Formation of light-reactive metabolites or impaired cellular protection:

• Hartnup syndrome: An autosomal recessive disorder characterized by impaired tubular and enteral absorption of certain amino acids, particularly tryptophan, with cerebellar symptoms, photodermatosis, and aminoaciduria. Pellagra-like photosensitive dermatitis

In the narrower sense of human genetics, photosensitivity syndromes primarily refer to rare inherited disorders characterized by defects in known DNA repair mechanisms such as nucleotide excision repair (NER), double-strand break repair (DSBR), base excision repair (BER), and mismatch repair (MMR). This group also includes disorders characterized by chromosomal instability and/or premature aging.