Higher rates of non-skeletal complications in achondroplasia compared to the general population: a UK matched cohort study using the CPRD database

Jeanne M. Pimenta; Moira Cheung; Melita Irving; Louise Mazzeo; Sarah Landis; Swati Mukherjee

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.


Specific complication*
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 • Hypertension	• Coronary disease • Myocardial infarction • Stroke
Developmental	8.81 (5.29-14.68)	• Developmental delay • Speech delay	•
ENT	3.03 (2.71-3.38)	• Enlarged tonsils • Hearing loss/deafness • Otitis media • Voice abnormality	• Sinusitis
Mental Health	1.58 (1.40-1.77)	• ADD/ADHD/adjustment disorder • Depression/anxiety • Self-harm/suicidal ideation	• Substance abuse
Metabolic	1.29 (1.10-1.50)	• Obesity	• Diabetes • Hyperlipidaemia
Neurological	7.72 (5.38-11.10)	• Seizures • Hydrocephalus/ventriculomegaly	• Dementia
Other	1.76 (1.65-1.87)	• Gastrointestinal issues • Headache • Pain-musculoskeletal	• 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.

ESPE Abstracts

P1-121