Table 5. [Autosomal Recessive Nucleotide Excision Repair Disorders Exhibiting Cutaneous Photosensitivity]. - GeneReviews®

Gene(s)	Disorder ¹	Clinical Features / Comment
ERCC1 ¹ ERCC2 ¹ ERCC5 ¹ ERCC6 ²	Cerebrooculofacioskeletal syndrome (COFS; OMIM PS214150)	Progressive neurologic disorder marked by microcephaly w/intracranial calcifications, growth failure, ocular findings (microcornea, cataracts, optic atrophy) & congenital joint contractures. Photosensitivity may occur w/concurrent cellular phenotype of UV sensitivity.
ERCC2 ¹ ERCC3 ¹ GTF2H5 GTF2E2 ³ MPLKIP ⁴	Trichothiodystrophy (TTD; OMIM PS601675)	Variable phenotype incl photosensitivity, ichthyosis, brittle hair w/"tiger tail" appearance under polarizing microscopy, intellectual impairment, short stature, microcephaly, dysmyelination of brain, & characteristic facial features of protruding ears & micrognathia. 20-fold ↑ risk of death before age 10 yrs, primarily from infections. Frequency of pregnancy complications & neonatal abnormalities is ↑ in ERCC2-related TTD but not in mothers w/XP w/different pathogenic variants in ERCC2. ⁵
ERCC2 ¹ ERCC3 ¹ ERCC4 ¹ ERCC5 ^1, 6, 7	XP / Cockayne syndrome (CS) complex	Assoc w/facial freckling & early skin cancers typical of XP & some features of CS (e.g., ID, spasticity, short stature, hypogonadism) but not skeletal dysplasia. Unlike XP, in which neuronal degeneration predominates, retinal pigmentary changes, calcification of basal ganglia, & dysmyelination typical of CS are observed in XP/CS.
ERCC2 ¹	COFS/TTD ⁸	Combined features of COFS & TTD. Hair may be short, brittle, & will demonstrate "tiger tail" banding under polarizing microscopy.
CS/TTD complex ⁸	Combined features of CS & TTD. Hair may be short, brittle, & will demonstrate "tiger tail" banding under polarizing microscopy.
XP/TTD complex ⁹	Phenotypic features of TTD w/clinical & cellular phenotype of XP. Unlike most people w/TTD, those w/XP/TTD may experience ↑ frequency of skin cancers.
ERCC6 ERCC8	Cockayne syndrome	CS type I (classic form): normal prenatal growth w/onset of growth & developmental abnormalities in 1st 2 yrs. When disease fully manifests, height, weight, & head circumference are far below 5th %ile. Progressive impairment of vision, hearing & CNS/PNS function → severe disability. Death typically in 1^st-2nd decade. As in XP, cells from those w/CS are hypersensitive to killing by UV, but CS cells have normal post-UV UDS. CS cells also have delayed recovery of RNA synthesis after UV exposure, reflecting their deficiency in transcription-coupled NER.
ERCC6 ¹⁰ ERCC8 ¹⁰ UVSSA ¹⁰	UV-sensitive syndrome	Mild photosensitivity w/o pigmentary abnormalities or apparent defects in CNS. Cells from affected persons have same transcription defects as those in persons w/CS.

Gene(s)

Disorder ¹

Clinical Features / Comment

ERCC1 ¹
ERCC2 ¹
ERCC5 ¹
ERCC6 ²

Cerebrooculofacioskeletal syndrome (COFS; OMIM PS214150)

Progressive neurologic disorder marked by microcephaly w/intracranial calcifications, growth failure, ocular findings (microcornea, cataracts, optic atrophy) & congenital joint contractures. Photosensitivity may occur w/concurrent cellular phenotype of UV sensitivity.

ERCC2 ¹
ERCC3 ¹
GTF2H5
GTF2E2 ³
MPLKIP ⁴

Trichothiodystrophy (TTD; OMIM PS601675)

Variable phenotype incl photosensitivity, ichthyosis, brittle hair w/"tiger tail" appearance under polarizing microscopy, intellectual impairment, short stature, microcephaly, dysmyelination of brain, & characteristic facial features of protruding ears & micrognathia. 20-fold ↑ risk of death before age 10 yrs, primarily from infections. Frequency of pregnancy complications & neonatal abnormalities is ↑ in ERCC2-related TTD but not in mothers w/XP w/different pathogenic variants in ERCC2. ⁵

ERCC2 ¹
ERCC3 ¹
ERCC4 ¹
ERCC5 ^1, 6, 7

XP / Cockayne syndrome (CS) complex

Assoc w/facial freckling & early skin cancers typical of XP & some features of CS (e.g., ID, spasticity, short stature, hypogonadism) but not skeletal dysplasia. Unlike XP, in which neuronal degeneration predominates, retinal pigmentary changes, calcification of basal ganglia, & dysmyelination typical of CS are observed in XP/CS.

ERCC2 ¹

COFS/TTD ⁸

Combined features of COFS & TTD. Hair may be short, brittle, & will demonstrate "tiger tail" banding under polarizing microscopy.

CS/TTD complex ⁸

Combined features of CS & TTD. Hair may be short, brittle, & will demonstrate "tiger tail" banding under polarizing microscopy.

XP/TTD complex ⁹

Phenotypic features of TTD w/clinical & cellular phenotype of XP. Unlike most people w/TTD, those w/XP/TTD may experience ↑ frequency of skin cancers.

ERCC6
ERCC8

Cockayne syndrome

CS type I (classic form): normal prenatal growth w/onset of growth & developmental abnormalities in 1st 2 yrs. When disease fully manifests, height, weight, & head circumference are far below 5th %ile. Progressive impairment of vision, hearing & CNS/PNS function → severe disability. Death typically in 1^st-2nd decade. As in XP, cells from those w/CS are hypersensitive to killing by UV, but CS cells have normal post-UV UDS. CS cells also have delayed recovery of RNA synthesis after UV exposure, reflecting their deficiency in transcription-coupled NER.

ERCC6 ¹⁰
ERCC8 ¹⁰
UVSSA ¹⁰

UV-sensitive syndrome

Mild photosensitivity w/o pigmentary abnormalities or apparent defects in CNS. Cells from affected persons have same transcription defects as those in persons w/CS.

From: Xeroderma Pigmentosum

GeneReviews^® [Internet].

Adam MP, Feldman J, Mirzaa GM, et al., editors.

Seattle (WA): University of Washington, Seattle; 1993-2024.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.