The first report of hypohidrotic ectodermal dysplasia caused by a novel mutation and accompanied with pathological femoral neck fracture

RATIONALE: Hypohidrotic ectodermal dysplasia (HED) is a rare inherited disorder characterized by hypohidrosis, hypotrichosis, and hypodontia. Most cases are caused by mutations in the EDA signaling pathway, whereas TP63-related HED is extremely rare. To our knowledge, this is the first reported case of HED caused by a novel TP63 mutation presenting with a pathological femoral neck fracture. PATIENT CONCERNS: A 31-year-old woman presented with progressive left hip pain and inability to bear weight for 2 weeks without a history of trauma. She had a lifelong history of hypohidrosis, heat intolerance, sparse hair, hypodontia, dry skin, and nail abnormalities. DIAGNOSES: Physical examination and radiographs revealed a displaced femoral neck fracture. Laboratory investigations demonstrated severe anemia, end-stage renal disease, secondary hyperparathyroidism, vitamin D deficiency, and osteoporosis. Whole exome sequencing identified a previously unreported heterozygous TP63 frameshift mutation (NM_001114982, c.1092_1093del, p.Asn364fs). Based on the clinical manifestations, laboratory findings, and genetic testing results, the patient was diagnosed with HED, pathological femoral neck fracture, end-stage renal disease, secondary hyperparathyroidism, osteoporosis, and severe anemia. INTERVENTIONS: After correction of anemia and electrolyte imbalance by hemodialysis and blood transfusion, the patient underwent uncemented bipolar hemiarthroplasty. OUTCOMES: She began partial weight-bearing ambulation on postoperative day 3 and was discharged on postoperative day 6. LESSONS: This case expands the mutational and phenotypic spectrum of TP63-associated HED by describing a previously unreported mutation presenting with a pathological femoral neck fracture and end-stage renal disease. It highlights the importance of early diagnosis, comprehensive genetic testing, multidisciplinary management, and regular follow-up for patients with HED.