{"doi":"10.1002/ajmg.a.62962","title":"Debilitating hip degeneration in trichothiodystrophy: Association with <scp><i>ERCC2</i></scp>/<scp><i>XPD</i></scp> mutations, osteosclerosis, osteopenia, coxa valga, contractures, and osteonecrosis","abstract":"Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder of DNA repair and transcription with developmental delay and abnormalities in brain, eye, skin, nervous, and musculoskeletal systems. We followed a cohort of 37 patients with TTD at the National Institutes of Health (NIH) from 2001 to 2019 with a median age at last observation of 12 years (range 2-36). Some children with TTD developed rapidly debilitating hip degeneration (DHD): a distinctive pattern of hip pain, inability to walk, and avascular necrosis on imaging. Ten (27%) of the 37 patients had DHD at median age 8 years (range 5-12), followed by onset of imaging findings at median age 9 years (range 5-13). All 10 had mutations in the ERCC2/XPD gene. In 7 of the 10 affected patients, DHD rapidly became bilateral. DHD was associated with coxa valga, central osteosclerosis with peripheral osteopenia of the skeleton, and contractures/tightness of the lower limbs. Except for one patient, surgical interventions were generally not effective at preventing DHD. Four patients with DHD died at a median age of 11 years (range 9-15). TTD patients with ERCC2/XPD gene mutations have a high risk of musculoskeletal abnormalities and DHD leading to poor outcomes. Monitoring by history, physical examination, imaging, and by physical medicine and rehabilitation specialists may be warranted.","journal":"American Journal of Medical Genetics Part A","year":2022,"id":275704,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9632,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":945748,"name":"Grant Randall","orcid":null,"position":1,"is_corresponding":false},{"id":945252,"name":"Alexandra Edelman","orcid":"0000-0002-2021-5266","position":2,"is_corresponding":false},{"id":945253,"name":"Rina Allawh","orcid":"0000-0002-2062-6233","position":3,"is_corresponding":false},{"id":815808,"name":"Michael Xiong","orcid":null,"position":4,"is_corresponding":false},{"id":432491,"name":"Deborah Tamura","orcid":"0000-0003-4812-5622","position":5,"is_corresponding":false},{"id":432492,"name":"Sikandar G. Khan","orcid":"0000-0001-9957-4132","position":6,"is_corresponding":false},{"id":681680,"name":"Elizabeth R. H. Rizza","orcid":"0000-0002-3833-890X","position":7,"is_corresponding":false},{"id":719346,"name":"James C. Reynolds","orcid":"0000-0003-1176-3030","position":8,"is_corresponding":false},{"id":109193,"name":"Scott M. Paul","orcid":"0000-0003-1274-6670","position":9,"is_corresponding":false},{"id":604285,"name":"Suvimol Hill","orcid":null,"position":10,"is_corresponding":false},{"id":432494,"name":"Kenneth H. Kraemer","orcid":"0000-0002-2689-3316","position":11,"is_corresponding":false},{"id":432493,"name":"John J. DiGiovanna","orcid":"0000-0002-2750-2313","position":0,"is_corresponding":true}],"reference_count":33,"raw_metadata":null,"created_at":"2026-07-19T00:28:21.971703Z","pmid":"36103153","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}