Experiences and treatment perspectives of adolescents and young adults with achondroplasia and caregivers: a qualitative interview study

Purpose

People with achondroplasia (ACH) experience numerous symptoms and impacts on health-related quality of life (HRQoL) and have varying perspectives on treatment. This study characterized the experiences of adolescents and young adults with ACH and caregivers to identify diagnoses, signs and symptoms, and HRQoL impacts associated with ACH and understand treatment perspectives, experiences, and expectations.

Methods

A qualitative interview study was conducted in the US and South Korea from February to June 2023. Participants were people with ACH aged 12–20 years and caregivers (aged ≥ 18 years) of people with ACH aged ≤ 20 years. Interviews explored signs, symptoms, impacts on HRQoL, and treatment perspectives. Interview transcripts were analyzed qualitatively, and key concepts were identified.

Results

In total, 30 participants were recruited (15 people with ACH; 15 caregivers). The most prevalent comorbid diagnoses were sleep apnea (n = 23, 77%), teeth misalignment (n = 20, 67%), obesity (n = 18, 60%), and ear infections (n = 17, 57%). The most common symptoms were pain and snoring (n = 25, 83% each). HRQoL impacts primarily involved physical functioning (n = 29, 97%), daily activities (n = 25, 83%), mobility/gait (n = 25, 83%), and social activities (n = 23, 77%). Increased height (n = 20, 67%) and reduced pain (n = 12, 40%) were the most frequently expected treatment benefits. Participants were generally satisfied with treatments but emphasized burdens such as frequent injections. No specific treatment side effects or risks were prominent.

Conclusion

People with ACH and caregivers prioritized treatments that increased height and reduced pain and wished less burdensome modes of administration were available. Findings may help guide future research and treatment development.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11136-026-04251-7.

Plain language summary

Achondroplasia is a condition that affects bone growth and causes shorter height. People with achondroplasia face many challenges in their day-to-day lives and have different views on and expectations about treatments. Understanding these experiences, views, and expectations is important for researchers to develop appropriate treatments to meet people’s needs. We interviewed 15 people (aged 12–20 years) with achondroplasia and 15 caregivers of people with achondroplasia in the United States and South Korea. People with achondroplasia were asked about symptoms, how achondroplasia affects their lives, experiences with treatment, and potential future treatments. Caregivers responded for the person with achondroplasia they cared for. Common health issues included sleep apnea, teeth misalignment, obesity, and ear infections, and the most common symptoms were pain and snoring. Impacts on quality of life mainly included difficulties with physical activities, walking, completing daily routines, and social activities. When asked about treatments, increased height and reduced pain were the most desired potential benefits. While people with achondroplasia and caregivers were generally happy with treatments, many wished for easier ways to take treatment, ideally with fewer injections. These findings may help guide future research and lead to better treatments to meet the needs of people with achondroplasia.

Supplementary Information

The online version contains supplementary material available at 10.1007/s11136-026-04251-7.

Introduction

Achondroplasia (ACH) is the most common form of short stature and has an estimated worldwide birth prevalence of 4.6 per 100,000 [1]. Short stature in people with ACH is characterized by disproportionate reduction in limb length relative to torso size, with additional skeletal manifestations including macrocephaly, elbow flexion contractures, trident hands, and leg bowing [2]. Signs and symptoms associated with ACH include back pain [3–9], obstructive sleep apnea [6, 10], fatigue [4, 5, 7], middle ear impairment, foramen magnum stenosis (FMS), spinal stenosis, bowed legs, and obesity [2, 11]. People with ACH experience physical limitations primarily involving neuromusculoskeletal and movement-related functions as defined by the International Classification of Functioning, Disability and Health [12]. Impacts on health-related quality of life (HRQoL) associated with ACH include difficulty with daily functioning, accessibility challenges, and effects on emotional and social well-being that may involve unwanted attention in public or being perceived as younger than true age [5, 8, 13]. Clinical care pathways and protocols are variable [14]. Surgical treatments for ACH may be used to improve specific complications such as pain, altered gait patterns, FMS, or sleep apnea [15, 16], whereas pharmacological therapies aim to counteract the effects of the mutation in fibroblast growth factor receptor 3 that is the underlying cause of ACH [16, 17].

To aid in treatment selection related to ACH, a robust understanding of patient perspectives and experiences of treatment is essential. Understanding treatment expectations, including desired benefits and concerns about burdens and risks, can help physicians engage in shared decision-making with people with ACH and caregivers on the optimal treatment strategy. Moreover, patient experience data play a growing role in health technology discussions and medical device development [18, 19] as well as in regulatory decision-making as related to patient-focused drug development [20]. Despite this, few previous studies have looked at individual experiences of ACH treatments or investigated potential treatment benefits and burdens from the perspective of people with ACH and caregivers.

This study aimed to characterize the experiences of adolescents and young adults with ACH and their caregivers to identify diagnoses, signs and symptoms, and HRQoL impacts associated with ACH and understand their perspectives on and expectations for treatment.

Methods

Study design

A qualitative study, involving one-on-one, semi-structured, 90-minute telephone interviews, was conducted in the US and South Korea from February to June 2023. This study was approved by the Salus Institutional Review Board in January 2023 (#23007-01) and performed in accordance with the Declaration of Helsinki of 1964 and its later amendments. Before completing study-related activities, all participants provided informed consent. People with ACH under 18 years of age provided assent, and their caregiver provided informed consent. A target sample size of approximately 12 people with ACH and 12 caregivers was considered sufficient to achieve concept saturation [21].

Study population

Participants were people with ACH aged 12–20 years and caregivers (aged ≥ 18 years) of people with ACH aged ≤ 20 years in the US and South Korea. Caregivers had spent at least 50% of nights in the past year with the person under their care. People with ACH or caregivers who had participated in an interventional clinical trial within three months of study enrollment were excluded.

Recruitment and interview scheduling

US participants were recruited through Global Perspectives, a specialist patient recruitment agency, using patient advocacy groups and patient panels. South Korean participants were recruited through Little Angels, a patient association group. In both cases, interested participants contacted the recruiter to be screened for eligibility. All screening responses, including ACH diagnosis, were self-reported. Efforts were made to reduce respondent burden by limiting the number of questions asked during screening. Due to the recruitment methods, some participants were likely dyads, where participating caregivers were the caregivers of participating people with ACH. However, the number of dyads was not recorded to ensure participant anonymity.

Interview guides

A targeted literature review was conducted, initially focusing on treatment preference studies of people with ACH. None were found, and thus the review was refocused on studies of patient-reported outcomes related to ACH, symptoms, complications, and HRQoL impacts [3–10, 13, 22–28]. Based on the literature review, two semi-structured guides were developed: one for people with ACH and one for caregivers (Supplemental Appendix). Differences between the guides were minimal. Interviewers used the guides to characterize people’s experiences of ACH, their treatment experiences (including what, if any, surgical interventions had been undertaken), and expectations for future treatments. Each guide included an introduction to the session followed by open-ended questions and specific probes designed to facilitate discussion and maintain consistency across interviews.

Interview procedures

Telephone interviews were conducted by qualified staff experienced in interview methods who were trained on the interview guides. Each interview was conducted in the participant’s native language (English or Korean). For people with ACH under 18, caregivers were allowed to be present during the interview but were asked to refrain from contributing. One interview was conducted per participant. All interviews were audio recorded.

Interviewers asked open-ended questions and then probed on specific signs and symptoms of ACH, impacts on HRQoL, which symptoms or impacts were most bothersome to manage, and perspectives and experiences of treatment. Between interviews, minor updates were made to the interview guides (e.g., based on initial interview responses, additional probes related to common ACH symptoms were added). All modifications to the wording of the guides were documented (Supplemental Appendix).

After the interview, participants completed brief online sociodemographic and clinical questionnaires. Caregivers completed questionnaires about themselves and the person with ACH they cared for. Participants were remunerated for their time in local currency. Interview recordings were transcribed, and Korean transcripts were translated into English.

Data processing and analysis

Interview transcripts were reviewed for quality assurance and to ensure that all personally identifiable information was removed before analysis. Coding frameworks based on key themes from the interview guides and concepts identified from the literature review were developed. A combined deductive and inductive thematic analysis was conducted while reviewing the transcripts, which allowed the initial coding frameworks to be modified as new themes and concepts emerged during the interviews. Concept saturation was monitored throughout. The first transcript was coded by three researchers and compared during a coding alignment review meeting to assess reliability and consistency of coding for the remaining transcripts. Subsequent transcripts were independently coded, with regular meetings held to discuss arising results and themes and resolve inconsistencies in the use of codes. Qualitative analysis was conducted using ATLAS.ti version 22 (ATLAS.ti Scientific Software Development GmbH, Berlin, Germany). Descriptive statistics characterizing the sample were generated using R version 4.4.1.

Results

Demographic and clinical characteristics

Thirty participants were recruited: 15 people with ACH (n = 10 US, n = 5 South Korea) and 15 caregivers of people with ACH (n = 10 US, n = 5 South Korea) (Table 1). People with ACH had a mean age of 14.9 (standard deviation [SD]: 2.3) years and were near-evenly split between female (n = 7, 46.7%) and male. People with ACH in the US were mostly White (n = 8, 80.0%) (South Korean participants were not asked about racial background). Mean time since ACH diagnosis was 14.7 (SD: 3.0) years, and the median number of reported complications per person was 2 (range: 0–6). Caregivers had a mean age of 43.4 (SD: 5.6) years. US caregivers were mostly White (n = 7, 70%). Caregivers also reported that the people with ACH under their care had a mean age of 8.1 (SD: 4.1) years, were mostly female (n = 9, 60%), and (in the US) were mostly White (n = 7, 70%). Mean time since ACH diagnosis was 7.8 (SD: 3.5) years, and the median number of reported complications per person was 3 (range: 0–5). All caregivers were parents of children with ACH, and almost all (n = 14, 93.3%) were mothers. Two (13.3%) caregivers reported having ACH themselves. Concept saturation for both people with ACH and caregivers was met.

Table 1.

Self-reported participant demographic and clinical characteristics

Characteristic	People with ACH (n = 15)	Caregivers (n = 15)	People under caregivers’ care (n = 15)
Age in years
Mean (SD)	14.9 (2.3)	43.4 (5.6)	8.1 (4.1)
Range	12.0–20.0	32.0–52.0	3.0–15.0
Sex at birth, n (%)
Female	7 (46.7)	14 (93.3)	9 (60.0)
Racial background, n (%) a b
White	8 (80.0)	7 (70.0)	7 (70.0)
Black or African American	1 (10.0)	1 (10.0)	2 (20.0)
Asian or Asian American	1 (10.0)	2 (20.0)	2 (20.0)
Panamanian	1 (10.0)	0 (0.0)	0 (0.0)
Native Hawaiian or Pacific Islander	0 (0.0)	0 (0.0)	1 (10.0)
Prefer not to say	0 (0.0)	2 (20.0)	2 (20.0)
Employment, n (%)
Full time	2 (13.3) c	5 (33.3)	NR
Part time	1 (6.7)	1 (6.7)	NR
Student	11 (73.3)	0 (0.0)	NR
Self-employed	0 (0.0)	4 (26.7)	NR
Unemployed	1 (6.7)	4 (26.7)	NR
Unable to work due to disability	0 (0.0)	1 (6.7)	NR
Education level, n (%)
Less than elementary/primary school	5 (33.3)	0 (0.0)	NR
Elementary/primary school	4 (26.7)	0 (0.0)	NR
High school	4 (26.7)	0 (0.0)	NR
Some college/university	0 (0.0)	5 (33.3)	NR
College/university (BA, BS)	2 (13.3) c	7 (46.7)	NR
Other	0 (0.0)	3 (20.0)	NR
Time since ACH diagnosis (years)
Mean (SD)	14.7 (3.0)	NA	7.8 (3.5)
Range	10.4–20.2	NA	2.9–13.5
Number of complications per person
Median (IQR)	2 (1–3)	NA	3 (2–3)
Range	0–6	NA	0–5

^a Data on race were collected from US participants only. Percentages are based on US participants (n = 10 people with ACH; n = 10 caregivers).

^b Responses were not mutually exclusive; total percentages may exceed 100%.

^c Two responses are suspected to have reported caregiver demographics, as the ages reported with these responses were 59 years and 37 years. These values were excluded from mean age and age range calculations for people with ACH (ages reported at screening were used instead).

Due to the small sample sizes, data from people with ACH and caregivers were combined rather than compared. Likewise, data from US and South Korean participants were aggregated; country-specific themes were not evaluated and were not an objective of this study

Diagnoses associated with ACH

The most commonly reported diagnoses associated with ACH were sleep apnea (n = 23, 77%; 10 people with ACH, 13 caregivers), teeth misalignment (n = 20, 67%; 8 people with ACH, 12 caregivers), obesity (n = 18, 60%; 9 people with ACH, 9 caregivers), ear infections (n = 17, 57%; 7 people with ACH, 10 caregivers), and FMS (n = 14, 47%; 4 people with ACH, 10 caregivers).

Common diagnoses were described by name or indirectly with descriptors (Table 2). Sleep apnea was described as snoring and difficulty breathing that interrupted sleep: one person with ACH commented that “our airway is a lot smaller than our head and our neck and since for me I have a bigger tongue, which makes it harder to breathe.” Participants described needing braces to fix teeth misalignment, typically reporting the front teeth as the most crooked; one caregiver noted that their daughter’s “jaws are narrow, her buck teeth grow out, and there isn’t enough room for her [adult] teeth to come out.” Participants described obesity as difficult to control; one person with ACH called weight management “very hard… I eat a normal portion but it’s harder for me to burn.” Participants described ear infections as common and sometimes requiring surgery; one caregiver described ear infections as “pretty common” for her daughter and anticipated to “hopefully rectify [earaches and ear pain] by putting the [grommets] back in her ears.”

Table 2.

Representative quotes on diagnoses, signs/symptoms, and HRQoL impacts associated with ACH

Participant	Topic discussed	Quote
US-PT-001	Diagnosis: sleep apnea	“For us, we have… Our airway is a lot smaller than our head and our neck and since for me I have a bigger tongue, which makes it harder to breathe, we have to put our head up when we sleep so that we can have the airflow going through our bodies when we sleep.”
KR-CG-002	Diagnosis: teeth misalignment	“My daughter has teeth misalignment. That’s why her two jaws are narrow, her buck teeth grow out, and there isn’t enough room for her teeth to come out. My daughter has crooked teeth.”
US-PT-001	Diagnosis: obesity	“Well, that [weight management] is very hard. To me, I eat a normal portion but it’s harder for me to burn. I seem like I eat a lot, but to me I eat a normal portion. It’s just harder to burn sometimes.”
US-CG-004	Diagnosis: ear infection	“Of course, with the ear infections, they are pretty common and recurrent for her, considering it is an unfortunate side effect of having achondroplasia as well. So, having ear aches and ear pain which we are going to rectify… hopefully rectify some of that by putting the [grommets] back in her ears but it’s… Mostly, she doesn’t really have any serious pain right now.”
US-CG-010	Diagnosis: FMS	“Yeah, so at five months she began arching her back and tilting her head up pretty frequently so we were seen by a neurosurgeon and she had cervical decompression in a C1 and C2 laminectomy at seven months old.”
KR-CG-005	Diagnosis: FMS	“…As a result of the MRI, doctor said that the pathway looked narrow, so we went to neurology. Afterwards, I was told that the space was small but she didn’t need surgery, but I was told that she needed to be followed up, so she had an MRI done every year until she was in the 3rd year … The doctor said that the inner room no longer grew, but rather became smaller, so we didn’t take a picture. The doctor showed me a picture and said that the foramen magnum stenosis improved from a wrinkled shape to a straightened shape after 1 year, and said that surgery would not be needed. I can’t remember exactly if it was one year or two years later. The doctor said that although the inner rooms were slightly enlarged, there were no other symptoms, so we should watch the hydrocephalus a little longer, so we watched until the 3rd grade.”
KR-CG-005	Signs/symptoms: pain	“When walking on the street outside, she takes a break and goes to a place like a chair where she can sit [because of pain]. And when my child is at home, I tell her to lie down when she says her back pain because she’s been sitting for a long time.”
KR-PT-003	Signs/symptoms: snoring	“My snoring is so loud that my mom can hear it all the way to the bedroom.”
US-CG-008	Signs/symptoms: fatigue	“He does get tired pretty easily… so we get the irritable side of him throughout the day… he goes to bed at 9 o’clock and he fights it, and you can tell he’s tired because he rubs his eyes.”
KR-CG-004	Signs/symptoms: walking/gait	“[Walking] is slow. Also, my child has a lot of flesh, and his legs are short and fleshy, so his gait itself is not as free as normal children … He takes some stress. When we walk together, other people go fast, but my child gets annoyed because he is late. I ask the child to go with me, and I call the child, but since it is not easy for ordinary people to keep pace with the child, he gets angry and stressed out.”
US-PT-001	HRQoL: physical functioning	“Oh yes, like running. I can’t run very quickly, so I can’t join most sports. I can’t jump because every time I jump, my head is so heavy that my neck… every time I go back down, my neck isn’t really able to support it if I go up and down. Because our necks are fragile because of how heavy our heads are, I can’t… I do tennis and stuff and golfing. It’s harder for us because our arms are smaller, but we don’t have that same motion.”
US-CG-011	HRQoL: social activities	“Well, from the point of view, a lot of people treat her like she’s a baby or she’s little. That influences how she behaves, and she doesn’t like that and it makes her angry, and then she has a hard time getting people to play with her. They don’t always want to play with her because she can’t keep up. And then everybody wants to hang out with her, but they don’t want to wait on her on the playground. It’s not that they’re intentionally being mean, they’re just into their own thing and she can’t keep up. So, I guess socially it affects her. Let’s see. She doesn’t seem to have any really close friends and I don’t know if that’s maybe why, so it is affecting her socially. And then when she plays, she can’t keep up with people, she gets tired easy. And she can’t do everything the other kids her age are doing. So, the thing is, I can’t let her play outside or walk up the street herself because people will think she’s a toddler and get upset. So, I have to go with her everywhere. She can’t really be independent within what’s accepted for a 7-year-old.”
US-PT-003	HRQoL: daily activities	“Maybe needing like a stool or something to reach a kitchen counter… Not to reach the kitchen counter, but to be able to do something at the kitchen counter, like make myself a sandwich or something like that. It’s not really a complication anymore but for driving, I need pedal extensions. So, because I have the extensions, it’s good now but I wouldn’t be able to just hop in someone else’s car and drive or something like that or vice versa, someone driving my car because of the extensions.”
US-PT-006	HRQoL: mobility/gait	“Well, there is the obvious of not being able to reach a lot of things. And most of the time that’s not that much of a problem because I can just ask or get a stool. But at times when I’m by myself or there’s nothing else to help me, it’s really hard to climb up and get the object I need. And when I meet people, they look at me strange and it’s really uncomfortable.”
KR-CG-005	HRQoL: emotional well-being	“Emotionally, the child cried a lot. As friends younger than her came in, but they were bigger than her. It was a time when she was in kindergarten, but she was in the eldest class, and when new younger friends came in, they were all taller than her, and her friends were also bigger than her, so she cried a lot at that time. She feels a lot of pressure when she has to do something in front of a lot of people, especially in a sports event or a presentation. My child doesn’t express that because she is different from others, but because she hears a lot about her short height, she cried a lot, saying, “Mom, why am I not tall?“.…“Why am I not tall. Why am I disabled? Why was I born this way?” she asked questions like this and we cried a lot together.”
US-CG-011	HRQoL: school	“Yeah. She’s tired, she’s sick a lot so she misses a lot of school which is impacting her academics. So, we try to work with her at home to try to catch back up, and she’s finally caught back up on the reading. And I think she’s pretty smart, so it’s been easy to catch up. But she’s missing a lot of stuff at school due to that. And the… let’s see. What was the question? How it affects her life?”

ACH, achondroplasia; CG, caregiver; FMS, foramen magnum stenosis; HRQoL, health-related quality of life; KR, Korea; PT, person with achondroplasia; US, United States

FMS was predominantly mentioned by caregivers using descriptors such as “cervical compression” or a “narrow pathway” at the base of the skull (Table 2). Participants frequently discussed how FMS required ongoing monitoring and had to be treated with surgery; one caregiver recalled how, at five months old, her daughter “began arching her back and tilting her head up pretty frequently, so we were seen by a neurosurgeon, and she had cervical decompression in a C1 and C2 laminectomy at seven months old.”

Other diagnoses included bowed legs (n = 7, 23%; 3 people with ACH, 4 caregivers), spinal stenosis (n = 6, 20%; 2 people with ACH, 4 caregivers), and short stature (n = 5, 17%; 3 people with ACH, 2 caregivers). Infrequent diagnoses such as kyphosis, scoliosis, and hydrocephalus were reported by four or fewer participants each.

Signs and symptoms of ACH

Pain and snoring (n = 25, 83% each; 12 people with ACH, 13 caregivers each) were the most common symptoms of ACH, with similar numbers of people with ACH and caregivers reporting each (Fig. 1). Pain was experienced in the legs, neck, hips, and back, typically after walking long distances or sitting in one position for an extended time; one caregiver noted how, “when walking on the street outside, [my daughter] takes a break and goes to a place like a chair where she can sit [because of pain]” (Table 2). Caregivers observed that the person under their care often described their pain by indicating the body area where pain occurred and expressed frustration or a desire to cease their current activity. Snoring was described as a loud noise disrupting other family members’ sleep; one person with ACH mentioned that “my snoring is so loud that my mom can hear it all the way to the bedroom.”

Fig. 1.

Signs and symptoms reported by participants (n = 30)

Fatigue and difficulties with walking/gait (n = 21, 70% each; 9 people with ACH, 12 caregivers each) were also common (Fig. 1). One caregiver noted how fatigue hindered their son’s daily physical activities: “he does get tired pretty easily… so we get the irritable side of him throughout the day” (Table 2). Challenges with weight exacerbated walking/gait difficulties; one caregiver commented: “my child has a lot of flesh, and his legs are short and fleshy, so his gait itself is not as free as normal children.”

Other signs and symptoms included numbness/tingling (n = 9, 30%; 4 people with ACH, 5 caregivers) and muscle weakness (n = 7, 23%; 5 people with ACH, 2 caregivers). Infrequent signs and symptoms such as fluid in ears, motor development, nasal congestion, and others were reported by 4 or fewer participants each (Fig. 1).

Impacts on HRQoL

Impacts of ACH on HRQoL fell into six categories: physical functioning, social activities, daily activities, mobility/gait, emotional well-being, and school (Fig. 2).

Fig. 2.

Impacts on health-related quality of life reported by participants (n = 30)

Impacts on physical functioning were reported by 29 participants (97%; 14 people with ACH, 15 caregivers). These included reduced ability for physical activity, delayed milestones, physical discomfort, and being perceived as younger than true age. Caregivers discussed delayed milestones and impacts of being perceived as younger than true age more frequently than people with ACH did.

Impacts on daily activities were reported by 25 participants (83%; 10 people with ACH, 15 caregivers). These included independence in daily activities, self-care activities, and reduced access in public settings. Most reports of limited self-care activities, poor sleep quality, discomfort during transportation, and medical appointment burden came from caregivers. However, driving difficulty was mentioned only by people with ACH.

Impacts on mobility and gait were reported by 25 participants (83%; 12 people with ACH, 13 caregivers), including difficulty reaching or bending for items, needing assistive devices or tools, and altered appearance when walking or running. Responses were similar between people with ACH and caregivers.

Impacts on social activities were reported by 23 participants (77%; 11 people with ACH, 12 caregivers). These included the inability to participate in activities with peers, receiving comments about height or physical appearance, difficulty making friends, bullying, and others. Responses were similar between people with ACH and caregivers.

Emotional impacts were reported by 19 participants (63%; 8 people with ACH, 11 caregivers), including feeling upset, worrying about body image, feeling frustrated/annoyed, anxiety, stress, and others. Moreover, caregivers discussed the person for whom they cared experiencing disappointment or discouragement or feeling scared.

Impacts on school were reported by 10 participants (33%; 5 people with ACH, 5 caregivers). These included needing adaptive measures or tools while at school, missed school due to ACH, or homeschooling due to safety concerns. Only caregivers mentioned impacts from missing school

Most bothersome diagnoses, symptoms, and HRQoL impacts

Across participants, the most bothersome diagnoses and symptoms to manage were pain (n = 12, 40%; 8 people with ACH, 4 caregivers), sleep apnea (n = 9, 30%; 1 person with ACH, 8 caregivers), and fatigue (n = 7, 23%; 4 people with ACH, 3 caregivers) (Fig. 3). Most mentions of pain as bothersome were from people with ACH, while all mentions of sleep apnea but one were from caregivers.

Fig. 3.

Most bothersome diagnoses and symptoms reported by participants (n = 30)

The most bothersome impacts of ACH on HRQoL involved physical functioning (n = 21, 70%; 14 people with ACH, 7 caregivers), social activities (n = 18, 60%; 6 people with ACH, 12 caregivers), mobility/gait (n = 15, 50%; 13 people with ACH, 2 caregivers), and daily activities (n = 12, 40%; 3 people with ACH, 9 caregivers) (Fig. 4). Several people with ACH discussed how their height impacted their independence and ability to socialize with peers (Table 2). People with ACH more frequently reported impacts on physical functioning and mobility/gait, whereas caregivers more frequently reported impacts on social activities and daily activities. People with ACH mentioned reduced capacity for physical activity and difficulty reaching/bending as the most bothersome impacts, with one noting “I want to stay as active as [peers] are, but it’s just hard for me to stay as active… I wish I could be taller so I can grab things and cook.” Caregivers mentioned attention in public, inability to participate with peers, and independence, with one caregiver emphasizing how “people staring” and “not being able to play group sports” upset their child.

Fig. 4.

Most bothersome health-related quality of life impacts reported by participants (n = 30).

Treatment experiences

When asked about treatment experiences, 15 people with ACH and 14 caregivers (n = 29, 97%) reported surgical interventions for ACH, and four people with ACH and 12 caregivers (n = 16, 53%) reported non-surgical interventions. People with ACH mentioned feeling scared and/or worried about the surgical interventions but acknowledged that they could potentially improve symptoms: “if I hadn’t had the surgery then, I think I would regret it a lot” (Table 3). Similarly, caregivers reported feeling anxious and scared about their child undergoing surgical interventions; one caregiver described “a very terrifying feeling because you don’t know what to expect. Your spine is a very important thing, and they read you a very long list of possibilities that can happen, like becoming paralyzed.” Caregivers noted that many surgeries occurred when their child was too young to understand what was happening or recall it later. Additionally, 11 caregivers emphasized financial impacts of interventions: one South Korean caregiver noted that, “the medical expenses alone cost us more than 10 million [KRW, or about $7,000].”

Table 3.

Representative quotes on treatment benefits, burdens, and risks

Participant	Topic	Quote
US-PT-013	Treatment satisfaction	“I’m happy with the way leg lengthening is because achondroplasia’s a challenge of course, but like, reaching stuff and then you’re able to get taller, and then sometimes you’re able to get taller compared to someone that doesn’t have achondroplasia. They said I’ll be around 5 foot 10 inches to 6 foot tall once I’m done.”
US-CG-011	Treatment satisfaction	“I am [satisfied]. We’re taking this drug that was just approved last year, the [drug]. And it’s had a little bit… it’s increased her growth a little bit and it’s made her arms a little longer. So, I think it does help with the proportions a little bit, which helps with the toilet hygiene, but that’s pretty much the only treatment … We haven’t had any bad side effects from the [drug]. I do wish that it were not… We have to give her an injection every night, give her a shot, and she does not like that… She’ll tell us ‘Oh, I like being little. I don’t want the shot, I don’t mind being a little person’.”
KR-PT-003	Surgical interventions	“If I hadn’t had the surgery then, I think I would regret it a lot… [They would regret] That I’ll have to live with a short height.”
US-CG-008	Surgical interventions	“It’s a very terrifying feeling because you don’t know what to expect. Your spine is a very important thing and they read you a very long list of possibilities that can happen, like becoming paralyzed, all these different things. They say it’s very rare, but there’s always these possibilities with having a spinal surgery because it’s your nervous system for the most part. So, it controls all the nerves, and hearing that, it’s very terrifying and then when they’re checking them out, they ask you “Does he walk now? Does he sit up? Does he do this?” because he was so young in age. Then when he’s in the hospital recovering for those couple of days, they ask “Is he sitting? Has he moved his arms? Has he moved his legs? Is he doing things that he did before surgery?” Things like that, mobility things, because they’re wanting to make sure there’s no issue with other parts of the body because they’re doing the spine. So, it’s scary thinking oh did he do this before? Did he do that? So that made us very anxious. They had a lady come in and say a prayer with us before he went back for surgery. All kinds of medical releases. So, it puts us on edge, like this could be the last time you see your child, this could be the last time you see your child smile, things like this, so it’s a very scary feeling. But we trusted our doctor and they did great work, and he’s a happy, healthy boy still.”
KR-CG-002	Cost of surgical interventions	“I think it has much [financial] impact. When we analyzed the household situation for a year, the medical expenses alone cost us more than 10 million [KRW, or about $7,000].”
US-PT-013	Most important treatment benefits	“The height for more independence and quality of life. Second would be the later life effects like arthritis and soreness of the bones as in joint pain and back pain would be the third I’d say.”
US-CG-006	Most important treatment benefits	“Yeah, definitely height. Definitely there’s not too much pain. I know that there would be a little pain but not as much. Not like ongoing pain because I did research way back when, whenever they did those braces on your legs and that’s just too intense for me, so something like that, it’s really invasive. So, something that’s not as invasive and something that’s a little bit more discreet, to be honest, because I wouldn’t want everybody to know my child is getting the treatment or, you know… Something that’s a little bit more secretive to where it’s like, okay, you wouldn’t even know that he was even getting treatment”
US-PT-001	Treatment administration and burdens	“I just want pills, or even maybe needles and stuff like that. I don’t want anything that makes it that I have to be in bed for a while.”
US-CG-001	Treatment administration and burdens	“It would be a lot better if she could take a pill… Possibly something that she wouldn’t have to mix or reconstitute. Something that was already pre-set with an injectable liquid. Kind of like they have for insulin… Or even just dial it and give it to yourself. I guess just easier for a child. If she travels, we’ve been on trips and things, and we’ve had to pack a cooler and make sure that the drug, we had enough drug and that it was gonna stay cool and things like that…And maybe… she gets embarrassed and maybe discreetness would be great… Anything but an injection [laughs] that would be her top priority.”
KR-CG-001	Treatment side effects	“We, in general, now also hear a lot that if we take a lot of medicine, we will develop a tolerance, and if we take medicine for a long time, there will be side effects. My son is growing well now and has no pain, and he’s fine, but I’m afraid that because of taking the medicine, the organs inside will get a little worse or get weaker or something will hurt, so I’m afraid it will hurt elsewhere.”

CG, caregiver; KR, Korea; KRW, Korean won; PT, person with achondroplasia; US, United States

Of 23 participants who discussed treatment satisfaction, 7 people with ACH and 12 caregivers (n = 19/23, 83%) were satisfied with their current treatments. One person with ACH affirmed that “I’m happy with the way leg lengthening is … they said I’ll be around 5 foot 10 inches to 6 foot tall once I’m done” (Table 3). One caregiver described how a pharmacological intervention improved their daughter’s height: “it’s increased her growth a little bit and it’s made her arms a little longer. So, I think it does help with the proportions a little bit, which helps with the toilet hygiene.”

Treatment perspectives and expectations

When asked about expected benefits from treatment (including drug therapies and/or surgical interventions, as appropriate for each participant), participants most frequently reported increased height (n = 20, 67%; 11 people with ACH, 9 caregivers) and reduced pain (n = 12, 40%; 9 people with ACH, 3 caregivers). According to one person with ACH, the first treatment priority was “height for more independence and quality of life. Second would be the later life effects like arthritis and soreness of the bones as in joint pain and back pain would be the third” (Table 3). People with ACH, more often than caregivers, reported reduced pain and improved walking/gait as important benefits. Caregivers reported a wider variety of benefits, including growth, health/longevity, independence, and others.

Participants noted a lack of treatments that address height and proportional body growth without a burdensome mode of administration (Table 3). One caregiver expressed concern over “really invasive” treatments for increasing height, such as leg braces, and wished “more discreet” options were available “because I wouldn’t want everybody to know my child is getting the treatment.” Caregivers mentioned how injections were difficult for their child to tolerate, with one caregiver noting how “we have to give her an injection every night, give her a shot, and she does not like that… She’ll tell us ‘Oh, I like being little. I don’t want the shot, I don’t mind being a little person.’” Another US caregiver reported that her daughter wanted “anything but an injection [laughs] that would be her top priority.”

When asked about treatment risks and side effects that would concern them, participants gave varied responses (Table 3). Pain was most commonly reported as a concern (n = 6, 20%; 4 people with ACH, 2 caregivers), followed by vomiting (n = 4, 13%; 1 person with ACH, 3 caregivers). One caregiver described how “my son is growing well now and has no pain, and he’s fine, but I’m afraid that because of taking the medicine, the organs inside will get a little worse or get weaker or something will hurt, so I’m afraid it will hurt elsewhere.” Other risks or side effects of concern included headache, spinal effects, blood pressure impacts, swelling, general or bone weakness, and others, with each getting ≤ 2 responses.

Finally, 5 people with ACH and 9 caregivers (n = 14, 47%) distinguished between short- and long-term treatment benefits. Short-term benefits included increased height, increased limb length, reduced pain, increased walking distance, reduced fatigue, reduced impact on sleep, and improved tolerance of treatment. Long-term benefits included reduced number of doctor visits, improved physical impacts (e.g., movement, walking, and running), physical independence, reduced number of surgical interventions, and mitigation of future spinal problems.

Discussion

This study found a range of diagnoses, signs and symptoms, HRQoL impacts, and perspectives on treatment among people with ACH and their caregivers. By far the most desired treatment benefit was increased height. This was unsurprising considering the number of participants who discussed the impacts of height on independence, ability to socialize with peers, and daily activities. Previous studies on the impacts of ACH on social activities and daily functioning for children and adolescents found that difficulty reaching objects/high places were common impacts on daily functioning and that participation in sports or play and being treated as younger than true age were common social impacts [5, 8, 13]. Our findings build on these previous results by revealing how treatment burdens influence the perspectives of both people with ACH and caregivers. While increased height was the top treatment priority across participants, methods of treatment administration were also a major concern, and desire for more tolerable treatments with fewer injections was a recurring theme.

Pain was another common theme and the most bothersome symptom for people with ACH to manage. Reduced pain was the second-most desired treatment benefit after increased height, and reducing pain and avoiding new pain resulting from treatment were high treatment priorities. While previous studies have identified pain as a major symptom of ACH [6, 8], our results reveal how pain related to ACH weighed heavily on the minds of both people with ACH and caregivers and was a key determinant of treatment perspectives and expectations.

Difficulty sleeping was also commonly reported. Sleep apnea was the most commonly reported diagnosis and second-most bothersome diagnosis to manage, especially among caregivers. Likewise, snoring and fatigue were common symptoms, and sleep apnea was commonly reported by caregivers. Results aligned with previous findings, which identified sleeping difficulties as common themes observed among younger people with ACH and their caregivers [8]. Our study found that sleep apnea was especially bothersome for caregivers, but that sleeping difficulties—while common among people with ACH and quite bothersome for caregivers—were not a top treatment priority. These results underscore that people with ACH and caregivers must be considered together to fully understand the symptoms and diagnoses associated with ACH.

Impacts of ACH on HRQoL were varied. Many related to height or disproportionate limb length, such as reduced ability for physical activity, being perceived as younger than true age, or inability to run very fast, ride a bike, or drive a car. Socially, people with ACH were unable to fully participate in physical activities with peers, sometimes due to height restrictions in public places. Many impacts were attributed—directly or indirectly—to height, making it unsurprising that increased height was the most desired treatment benefit. In line with previous studies [5, 8], results showed that caregivers emphasized their child’s emotional well-being and social activities, feeling that participating with peers, handling negative comments and attention in public, and being perceived as younger than true age were major obstacles for their child to navigate. This illustrates the importance of including caregivers in studies of ACH, as people with ACH and caregivers together provide a more rounded picture of ACH impacts than would be obtained from people with ACH alone.

People with ACH and caregivers were generally satisfied with the care received to treat signs and symptoms of ACH. However, many desired less burdensome treatments with better tolerability. Caregivers especially mentioned treatment tolerability and reduced side effects as key benefits, indicating that caregivers may place greater importance on treatment tolerability than people with ACH do. Despite the consensus on increased height as the most desired treatment benefit, concerns about treatment risks and side effects were heterogeneous across participants. This suggests that perspectives on treatment may be shaped by a desire for increased height and reduced treatment burden more than by any single risk or side effect.

Study strengths included recruiting both people with ACH and caregivers, which enabled a more robust and well-rounded investigation of the impacts of ACH. People with ACH provided first-hand information on the impacts of ACH, while caregivers described specific signs and symptoms that younger people with ACH may have been unwilling or lacked the knowledge or recall ability to discuss. People with ACH and caregivers also emphasized different attributes of treatment, especially when discussing HRQoL impacts. This may broaden the range of perspectives captured in the results.

Study limitations include the potential for selection bias during recruitment, limiting the generalizability of the study. People with ACH/caregivers with less spare time may have been less likely to participate. Second, the small sample size, while appropriate for a rare disease with associated stigma, precluded subgroup analyses by country (US vs. South Korea), participant type (people with ACH vs. caregivers), or age group (younger adolescents [12–15 years], older adolescents [16–18 years], young adults [19–20 years]). Data from people with ACH and caregivers were combined rather than compared. Future studies with larger sample sizes may elucidate the differing perspectives on ACH impacts and treatment benefits across subgroups. Third, while concept saturation was monitored during coding and saturation for both people with ACH and caregivers was met, formal prospective saturation criteria were not pre-specified. Fourth, dyads (people with ACH and caregivers in the same family unit) were not tracked. Tracking dyads could have potentially deepened our analyses and informed our interpretation of the results. Fifth, while pain was a commonly reported symptom, the various types and sites of pain were not systematically differentiated, as this level of characterization was beyond the scope of the semi-structured interviews. Perspectives on different types of treatment (surgical or non-surgical) were not systematically differentiated for similar reasons.

Additional limitations should be noted. Updates to the interview guides between interviews limited consistency across interviews, though these updates (e.g., additional probes based on initial interview responses) were minor. The cross-sectional design captured participant responses at a single time point, whereas perspectives on ACH impacts and treatment options may evolve over time. Moreover, the young age of many people with ACH at the time of treatment may have limited their ability to recall specific treatment attributes. Many people with ACH also had caregivers present during their interview. Despite being encouraged to refrain from contributing, some caregivers provided input throughout, possibly biasing responses. Finally, all participant characteristics, including ACH diagnosis, were self-reported.

Conclusions

People with ACH and caregivers reported a range of signs, symptoms, and impacts on HRQoL. Participants were generally satisfied with the care received to address symptoms and diagnoses associated with ACH, with increased height and reduced pain being the most desired treatment benefits. However, participants desired less burdensome modes of treatment administration. Differences in responses between people with ACH and caregivers in this study underscore that perspectives from both groups ought to be considered to achieve a robust, holistic understanding of ACH experiences and treatment decision-making. These insights should guide future research and clinical development of treatments for ACH.

Supplementary Information

Below is the link to the electronic supplementary material.

Author contributions

All authors contributed to the study conceptualization and methodology. Formal analysis was performed by G.S.F., K.C., and M.Q. Investigation was carried out by J.M., K.I.B., and S.B. Resources were provided by C.R. Validation was conducted by K.I.B. Visualization was handled by C.R. and K.I.B. Project administration was handled by J.M., G.S.F., C.R., and S.B. Supervision was provided by J.M., C.R., K.C., M.Q., and S.B. Funding was secured by J.M. and S.B. All authors reviewed the draft manuscript, critically revised it for important intellectual content, and approved the final draft for publication. All authors agree to be accountable for all aspects of this work.

Funding

This study was funded by Sanofi.

Data availability

Data from this study are not publicly available but may be provided upon reasonable request.

Declarations

Ethics approval

This study was approved by the Salus Institutional Review Board on 20 January 2023 (#23007-01). This study was performed in accordance with the Declaration of Helsinki of 1964 and its later amendments. Before completing any study-related activities, participants provided informed consent to participate in the study. Participants under 18 years of age provided assent, and their caregiver provided informed consent. No investigational drugs, devices, or invasive procedures were administered or evaluated.

Competing interests

J.M. was an employee of Sanofi at the time this study was conducted and may hold shares or stock options in the company. C.R., K.I.B., and S.B. are current employees of Sanofi and may hold shares or stock options in the company. G.S.F., K.C., and M.Q. are employees of Evidera PPD, Thermo Fisher Scientific, which received funds paid by Sanofi to Thermo Fisher Scientific for work relating to this study.

Prior presentations regarding this research

Some results were previously presented in a poster at the American Society for Bone and Mineral Research (ASBMR) Annual Meeting, September 2024, Toronto, ON, Canada.