Objectives: Achondroplasia (ACH) is a rare, genetic skeletal dysplasia, resulting in impaired endochondral bone growth and leading to multisystem complications. We aimed to estimate rates of non-skeletal complications in ACH patients compared with general population controls.
Methods: Retrospective cohort study using UK Clinical-Practice-Research-Datalink (CPRD-GOLD), identifying an ACH cohort. Study index date was defined as ACH first record between 01/01/1987-31/12/2018. ACH cases were index date matched (1: 4) by age, sex, general practitioner (practice-level) and linkage ability to Hospital Episode Statistics database with control patients, defined as those without evidence of skeletal/growth disorders. Read codes defined complications of interest based on ACH literature; we calculated event rates per 100 person-year and rate ratios [RR] (95% confidence intervals, CI) to compare cohorts.
Results: We identified 541 ACH cases and 2,052 matched controls: 51% female, mean age 29 years (y), range 0-94y at index date. Mean follow-up time was 14.5y for ACH cases and 19.1y for controls. The rate of complications across a range of body systems was significantly higher among ACH patients than matched controls (range RR=1.18 for cardiovascular conditions to RR=8.81 for developmental conditions) [see Table]. Complications differed by ages when compared to controls; e.g. rates of developmental issues, ENT (otitis media/tonsils) and apnoea were higher in children, cardiovascular conditions, depression and seizures in adults, and musculoskeletal pain and hearing loss significantly affected both.
|Body system||RR (95% CIs)||Statistically significantly higher RR in ACH compared to controls||No difference in RR between ACH cases and controls|
|Cardiovascular||1.18 (1.08-1.30)|| Chest pain/angina
| Coronary disease|
|Developmental||8.81 (5.29-14.68)|| Developmental delay
|ENT||3.03 (2.71-3.38)|| Enlarged tonsils
|Mental Health||1.58 (1.40-1.77)|| ADD/ADHD/adjustment disorder
| Substance abuse|
|Metabolic||1.29 (1.10-1.50)|| Obesity|| Diabetes|
|Neurological||7.72 (5.38-11.10)|| Seizures
|Other||1.76 (1.65-1.87)|| Gastrointestinal issues
| Sexual health/gynaecological issues|
|Respiratory||4.16 (2.99-5.81)|| Apnoea/sleep disordered breathing|| Sleep disorder|
|*Specific conditions with <5 events are not shown in Table but contributed to body system total: motor delay (Developmental); middle ear dysfunction and tracheomalacia/bronchomalacia (ENT); other mental health (Mental Health); craniocervical stenosis, failure to thrive, subdural haematoma (Neurological)|
Conclusion: This study illustrates that ACH patients have significant non-skeletal multisystemic complications when compared to an appropriate matched general population cohort which are seen throughout the lifespan.
22 Sep 2021 - 26 Sep 2021