Congenital photosensitivity Xeroderma pigmentosa It is a very rare disorder of congenital photosensitivity. 8O& of patients have a defect in DNA excision repair (classical XP), 2O%have a defect in daughter strand repair (XP variant) .Patients often present in childhood after suffering an exaggerated sunburn response. As patients get older, they develop severe photo damage & multiple skin cancers. Eye & neurological complications & multiple skin cancer, Eye & neurological complications are frequently seen, . The gold standard for diagnosis is UV irradiated skin fibroblast culture, photo provocation & genetic testing are helpful in some cases. The treatment is with vigorous photo protection, cancer surveillance & psychological support. Trichothiodystrophy Is another very rare recessive disorder of congenital photosensitivity. Up to 5O% of patients have a defective nucleotide excision repair showing overlap with XP. The degree of photosensitivity is variable& There is NO increased risk of skin cancer. Other features include chronic ichthyosis

Trichthiodystrophy J. Investigative Derm. 126: 2147, 2OO6 B. TTD hair displaying altternating light & dark tiger tail bands using polarizing microscope– C,f: Trichoschisis---d,g :Trichorexisis nodosa like fracture– e: ribbon like flattening– J,K: Undulating hair fiber

Congenital photosensitivity (continue) Sparse brittle hair, typical facies, short stature , mental retardation, erythroderma, eczema, multiple infections, cataracts, dental caries & hypoplastic nails. TTDNI gene mutations are seen in trichodystrophy. Diagnosis is made with UV irradiated skin fibroblast culture, monochromator testing is normal Cockayne syndrome It is a congenital disorder that may also overlap with XP showing photosensitivity, It has autosomal recessive inheritance with significant variation in phenotypic severity. Patients often present a few hours after sun exposure when they develop erythematous rash. Over time the rash may lead to pigmentation & scarring although there is no increase risk of skin cancer. Other features include short stature, mental retardation, large hands, feet & ears, eye problems & deafness. The photosensitivity resolves with age but prognosis is very poor with death before the age of 2O from progressive neurological demyelination

Cockayne syndrome

Congenital photosensitivity (continue) Rothmund- Thomson syndrome It is a rare autosomal recessive congenital syndrome related to a DNA helicase mutation. It is characterized by the development of prominence poikiloderma within the first year of life. Other features include photosensitivity , warty hyperkeratosis, cataracts, short stature, skeletal dysplasia & increased risk of Bowen’s disease & osteosarcoma. The gene responsible for Rothmund- Thomson syndrome is RecQL4. Kindler syndrome It is another rare autosomal recessive congenital photosensitivity syndrome with poikiloderma. Mutation in the Kind-I gene lead to a defect in actin binding in the extra cellular matrix. Patients develop blistering & skin fragility in infancy that include progressive & generalized pokiloderma, diffuse cutaneous atrophy, palmer hyperkeratosis, gingivitis, urethral, esophageal & anal stenosis

Rothmund –Thomson syndrome

Congenital photosensitivity (continue) Smith- Lemi –Opitz syndrome It is an autosomal recessive congenital disorder of cholesterol synthesis. Two third of patients photosensitivity with an exaggerated sunburn response to UVA. Other features include mental retardation, ambiguous genitalia, dysmorphic facies, failure to thrive, cleft palate, congenital heart disease & polydactyly. DHCR7 mutations are seen in Smith-Lemi- OPitz syndrome. Treatment include photoprotection and a high cholesterol diet. Bloom’s syndrome It is another autosomal recessive congenital photosensitivity disorder. It is rare & most commonly seen in Jews, Features include groth retardation, typical facies, telangiactasia & erythema of sun exposed skin, hyper & hypo-pigmentation & significant immunodefeciency.There is very high risk of malignancy especially leukemia, gastrointestinal, breast and skin cancer. A mutation is seen in the BLM gene that has a role in DNA replication forks

Smith-Lemi Opitz syndrome

Bloom syndrome