Impact of short stature on quality of life: A systematic literature review.

OBJECTIVE: We sought to obtain a better understanding of the burden of short stature using a systematic literature review. METHODS: Studies of the burden of short stature, of any cause in adults and children, were searched using Embase, MEDLINE and Cochrane databases in April 2020, capturing publications from 2008 onwards. Case series and populations with adult-onset growth hormone deficiency (GHD) were excluded. RESULTS: Of 1684 publications identified, 41 studies (33 in children, 8 in adults) were included. All studies assessed human burden. Most study populations in children included short stature due to GHD, idiopathic short stature (ISS) and short stature after being born small for gestational age (SGA). In these populations, four studies showed that quality of life (QoL) in children with short stature was significantly worse than in children with normal stature. A significant association between QoL and short stature was observed in children with chronic kidney disease (CKD) (3 studies), achondroplasia (1 study) and transfusion-dependent ß-thalassaemia (1 study), and in samples with mixed causes of short stature (3 studies). Three studies (one in GHD/ISS/SGA and two in CKD) found no significant association between short stature and QoL, and several studies did not report statistical significance. Approximately half of adult studies showed that QoL was reduced with short stature, and the other half showed no association. Two studies, one in adults with Prader-Willi syndrome and one in children with GHD, suggested a potential association between short stature and poorer cognitive outcomes. Three studies demonstrated an increased caregiver burden in parents of children with short stature. CONCLUSIONS: Evidence suggests that, compared with those with normal stature, children and adults with short stature of any cause may experience poorer QoL. Further research could extend our understanding of the human burden in this field.

Pubertal growth in height, sitting height and leg length in achondroplasia.

Background: Children with achondroplasia (ACH) appear to lack a pubertal growth spurt in height.Aim To explore the growth spurt in height and its segments sitting height and leg length, in a large sample of ACH cases using growth curve modelling.Subjects and methods: Height and sitting height were measured longitudinally in ACH children, and the data were analysed using the SITAR (SuperImposition by Translation and Rotation) growth model, which estimates a mean growth curve and random effects for individuals defining differences in size, pubertal timing and intensity.Results: Out of 402 ACH children, 85 boys and 75 girls aged 7-20 years had respectively 529 and 454 measurements of height and sitting height, with leg length calculated by difference. SITAR analysis identified peaks in mean height velocity at 13.3 and 11.3 years in boys and girls, with peak velocities of 4.3 and 4.4 cm/year. Mean peak velocity for sitting height was 3.0 cm/year, but leg length showed no peak. The SITAR models explained 92% to 99% of the cross-sectional variance.Conclusion: ACH children do experience a growth spurt in puberty, but only half that of control children. The spurt is due entirely to sitting height, with no leg length spurt.

Craniocervical junction issues after infancy in achondroplasia.

More information is available concerning risks of craniocervical junction issues in infancy than at later ages. Therefore, we elected to quantify the risks at greater than 1 year of age through a retrospective analysis of 477 individuals with achondroplasia using a REDCap database. Evaluation of these 477 individuals revealed 77 (16.1%) who had pathologic neurologic manifestations after 1 year of age related to the craniocervical junction. Within this subpopulation of 77 individuals, 43 (55.8%) underwent craniocervical decompression surgery, or 9.0% of the total population. Whether decompressed or not, most individuals with craniocervical junction issues after infancy had a normal outcome, without long-term neurological sequelae (57/77, 74.0%). The remaining 20 had various long-term neurological issues. This is the first cohort based estimate of risks related to the upper cervical spine in individuals with achondroplasia specifically beyond infancy.

Assessing physical symptoms, daily functioning, and well-being in children with achondroplasia.

This study's purpose was to provide qualitative evidence to support the development of two observer-reported outcome measures assessing the physical symptoms/complications of achondroplasia in children and impacts on children's quality of life. Individual/focus group concept elicitation interviews were conducted with parents of children aged 2 to <12 years with achondroplasia and experts. Qualitative analysis of transcripts, based on an adapted grounded theory approach, informed item generation and measure development. Cognitive debriefing (CD) interviews were conducted with parents to confirm relevance and understanding. Thirty-six parents participated in concept elicitation interviews. The analysis identified major physical symptoms/complications and impacts of achondroplasia, which informed the development of the Achondroplasia Child Experience Measures (ACEMs): ACEM-Symptom and ACEM-Impact. ACEM-Symptom was comprised of eight major symptoms/complications including pain (58%), ear infections/fluid in ear (56%), and low stamina/tiring easily (56%). ACEM-Impact consisted of 31 major impacts in the domains of daily functioning, emotional well-being, social well-being, and need for assistance/adaptive devices. Impacts on functioning included difficulty reaching objects/high places (89%) and toileting (67%). Emotional impacts included feeling different (53%) and feeling frustrated/annoyed (47%). Social impacts included difficulty participating in sports/physical play (86%) and being treated as younger than age (83%). Following CD interviews with 16 additional parents, validation-ready ACEM measures were generated. The study improves our understanding of the experiences of children with achondroplasia and provides evidence supporting the content validity of the ACEMs. Validated ACEMs may be used to assess potential benefits of future treatments for comorbidities of achondroplasia.

Quality of life in adults with achondroplasia in the United States.

Studies examining quality of life (QoL) in adults with achondroplasia are limited. We report on QoL and psychiatric illness diagnoses in a modern cohort of adults with achondroplasia. SF-36 Health Survey scores from adults with achondroplasia were compared to general population scores. Demographics, physical measurements, and psychiatric illness diagnoses were recorded from medical records. The achondroplasia population had lower scores than the general population in all categories. Most people with achondroplasia (56%) had a diagnosed psychiatric illness. Those with a diagnosed psychiatric illness had lower scores in physical functioning, role limitations due to physical and emotional health, and mental health. Pain, energy/fatigue, and general health scale scores were roughly equivalent (<2 points difference). Social functioning was >15 points higher in individuals with psychiatric illness diagnoses. Adults with achondroplasia report significantly lower physical and mental well-being and had nearly 3× the rate of psychiatric illness diagnosis than the general population, highlighting the importance of total care for this population. Healthcare providers must understand the physical and mental comorbidities of achondroplasia, beyond short stature and orthopedic issues, so they can proactively improve QoL across the lifespan for patients and families.

Clinical charts for surveillance of growth and body proportion development in achondroplasia and examples of their use.

Clinical surveillance of infants and children with achondroplasia necessitates syndrome-specific charts due to extreme short stature with deviating body proportions. Height, arm span and leg length develop far below normal population ranges. We present growth and body proportion charts for ages 0-20 years, constructed from semi-longitudinal standardized measurements of about 450 children, along with some examples of achondroplasia typical and atypical growth pattern. We combine head circumference, height and weight for 0-4 years into one (infancy) page and height and weight for 4-20 years in another (childhood-adolescence) using nonlinear axes to account for the rapidly decreasing growth velocity. Similarly, weight and BMI are based on nonlinear axes to balance wide SD-channels at higher and narrow SD-channels at lower levels of weight/BMI. Charts for following sitting height, sitting height/height ratio, arm span, leg and foot length are also presented. Clinical examples illustrating the applicability of the charts include cases of extreme prematurity, extreme head circumference development before and after shunting, achondroplasia complicated by chromosomal or additional genetic abnormality and by growth hormone deficiency as well as of evaluating growth promoting therapy.

Physical fitness and activity level in Norwegian adults with achondroplasia.

This cross-sectional Physical Fitness Study compared cardiorespiratory fitness (VO2 peak), six-minute walk test (6MWT), muscle strength (30sSTS), balance (BESS), and self-reported physical activity level (IPAQ) in Norwegian adults with achondroplasia (ACH) to reference values of average-statured individuals. The feasibility of the physical fitness tests and IPAQ was explored. Forty-three adults (22 women) participated. Mean age was 38 years (range 16-69 years). Mean differences (95% CI) for men and women with ACH compared to reference values were: VO2 peak. -7.0 m/min/kg (-13.6 to -0.5, p = .037), and - 7.9 ml/kg/min (-11.6 to -4.3, p < .001); 6MWT -270.8 m (-340.4 to -201.2, p < .001), and - 196.7 m (-244.3 to -149.0, p = .001); 30sSTS -4.6 repetitions (-7.8 to -1.5, p = .006), and - 1.1 repetitions (-3.4 to 1.1, p = .335). There were no differences within ACH participants, except for VO2 peak, where men performed better. Sufficient physical activity (> 600 metabolic equivalent of task weekly) was achieved by 79% of the participants. The feasibility of the 6MWT and 30sSTS was good. There was a strong correlation between the VO2 peak and 6MWT (men: r = 0.63, p = .007; women: r = 0.71, p < .001). The findings indicate that the 6MWT and 30sSTS test are useful in assessing functional exercise capacity and muscle strength in adults with ACH.

Growth in achondroplasia, from birth to adulthood, analysed by the JPA-2 model.

OBJECTIVES: In general population, there are three phases in the human growth curve: infancy, childhood and puberty, with different main factors involved in their regulation and mathematical models to fit them. Achondroplasia children experience a fast decreasing growth during infancy and an "adolescent growth spurt"; however, there are no longitudinal studies that cover the analysis of the whole post-natal growth. Here we analyse the whole growth curve from infancy to adulthood applying the JPA-2 mathematical model. METHODS: Twenty-seven patients, 17 girls and 10 boys with achondroplasia, who reached adult size, were included. Height growth data was collected from birth until adulthood. Individual growth curves were estimated by fitting the JPA-2 model to each individual's height for age data. RESULTS: Height growth velocity curves show that after a period of fast decreasing growth velocity since birth, with a mean of 9.7 cm/year at 1 year old, the growth velocity is stable in late preschool years, with a mean of 4.2 cm/year. In boys, age and peak height velocity in puberty were 13.75 years and 5.08 cm/year and reach a mean adult height of 130.52 cm. In girls, the age and peak height velocity in puberty were 11.1 years and 4.32 cm/year and reach a mean adult height of 119.2 cm. CONCLUSIONS: The study of individual growth curves in achondroplasia children by the JPA-2 model shows the three periods, infancy, childhood and puberty, with a similar shape but lesser in magnitude than general population.

A spatio-temporal and kinematic description of self-selected walking in adults with Achondroplasia.

BACKGROUND: Achondroplasia is characterised by a shorter appendicular limb to torso ratio, compared to age matched individuals of average stature (controls). Despite the well documented shorter leg length of individuals with compared to controls, there are few complete descriptions of gait kinematics reported for the population. AIM: The aim of this study was to report the spatio-temporal and kinematic characteristics of self-selected walking (SSW) in a group with Achondroplasia (N = 10) and age matched group without Achondroplasia (controls, N = 17). METHOD: Whole body 3D analysis of both groups was conducted using a 14 camera VICON system. Spatio-temporal and kinematic variables were determined through a Plug-in-Gait model. SSW was obtained from an average of three trials equating to a total of ∼120 m walking. RESULTS: The group with Achondroplasia were 23 % slower (P < 0.001), had a 29 % shorter stride length (P < 0.001) and a 13 % higher stride frequency (P < 0.001) compared to controls. There were no differences in time normalised temporal measures of left toe off (P = 0.365), right heel contact (P = 0.442) or the duration of double support (P = 0.588) between groups. A number of discrete joint kinematic differences existed between groups, resulting in the group with Achondroplasia having more 'flexed' lower limbs than controls throughout the gait cycle. CONCLUSION: Differences in absolute spatio-temporal variables between groups is likely due to the shorter leg length of the group with Achondroplasia, while their more flexed position of the lower limbs may facilitate toe-clearance during the swing phase.

Improvement in ventriculomegaly following cervicomedullary decompressive surgery in children with achondroplasia and foramen magnum stenosis.

The role of cervicomedullary decompression (CMD) in the care of hydrocephalic achondroplastic children who present with simultaneous foramen magnum stenosis is not well understood. We sought to determine the percentage of symptomatic achondroplastic children with foramen magnum stenosis who had stabilization or improvement in ventriculomegaly following CMD. The authors retrospectively reviewed the records of pediatric patients at Cedars-Sinai Medical Center with achondroplasia and signs of progressive ventriculomegaly who underwent CMD for symptomatic foramen magnum stenosis between the years 2000 and 2018. Clinical outcomes included changes in fontanelle characteristics, head circumference (HC) percentile, and incidence of ventriculoperitoneal (VP) shunting. Radiographic outcomes measured included changes in Evans ratio. We excluded individuals who were shunted before CMD from our study. Sixteen children presented with symptomatic foramen magnum stenosis and full anterior fontanelle or jump in the HC percentiles. Two children underwent placement of a VP shunt before decompressive surgery and were excluded from further analysis. Of the remaining 14 children who underwent CMD, 13 (93%) showed softening or flattening of their fontanelles post-operatively. Ten of these 14 children had both pre- and post-operative HC percentile records available, with 8 showing increasing HC percentiles before surgery. Seven of those eight children (88%) showed a deceleration or stabilization of HC growth velocity following decompression of the foramen magnum. Among 10 children with available pre- and post-operative brain imaging, ventricular size improved in 5 (50%), stabilized in 2 (20%), and slightly increased in 3 (30%) children after decompression. Two children (14%) required a shunt despite decompression of the foramen magnum. A significant proportion of children with concomitant signs of raised intracranial pressure or findings of progressive ventriculomegaly and foramen magnum stenosis may have improvement or stabilization of these findings following CMD. CMD may decrease the need for VP shunting and its associated complications in the select group of hydrocephalic children with achondroplasia presenting with symptomatic foramen magnum stenosis.

Trevor's disease of the distal radioulnar joint in two children with achondroplasia.

Two children with achondroplasia who developed an abnormal bony outgrowth at the distal radioulnar joint (DRUJ), indistinguishable from an osteochondroma on histology, but the radiographic appearance, location, and asymmetry suggested the rare diagnosis of dysplasia epiphysealis hemimelica (DEH or "Trevor's disease"). One child experienced symptomatic relief with surgical excision and one was observed clinically due to lack of significant symptoms. These are the first presented cases of DEH in achondroplasia, both affecting the DRUJ. Due to the infrequency of DEH, more research is needed to better understand the potential connection to achondroplasia. For management, we suggest shared surgical decision making based on symptoms.

Current knowledge of medical complications in adults with achondroplasia: A scoping review.

This article provides an overview of the current knowledge on medical complications, health characteristics, and psychosocial issues in adults with achondroplasia. We have used a scoping review methodology particularly recommended for mapping and summarizing existing research evidence, and to identify knowledge gaps. The review process was conducted in accordance with the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews). The selection of studies was based on criteria predefined in a review protocol. Twenty-nine publications were included; 2 reviews, and 27 primary studies. Key information such as reference details, study characteristics, topics of interest, main findings and the study author's conclusion are presented in text and tables. Over the past decades, there has only been a slight increase in publications on adults with achondroplasia. The reported morbidity rates and prevalence of medical complications are often based on a few studies where the methodology and representativeness can be questioned. Studies on sleep-related disorders and pregnancy-related complications were lacking. Multicenter natural history studies have recently been initiated. Future studies should report in accordance to methodological reference standards, to strengthen the reliability and generalizability of the findings, and to increase the relevance for implementing in clinical practice.

Weight gain velocity in infants with achondroplasia.

There are virtually no data regarding appropriate oral intake in infants with dwarfing disorders such as achondroplasia, nor is there clear information regarding appropriate weight gain velocity in this population. Yet, these individuals are at increased risk for both early failure to thrive and, later in life, for obesity. Having appropriate expectations regarding weight gain and reasonable goals in management is imperative. We sought to clarify the rate of weight gain in infants with achondroplasia during the first year of life through analysis of data from 60 infants with achondroplasia seen at least twice during the first year of life in the Midwest Regional Bone Dysplasia Clinic, University of Wisconsin-Madison between 1998 and 2018. The mean weight gain velocity during the first 3 months was 23 g/day which contrasts with 30 g/day in average statured infants. Mean weight gain from 0 to 12 months of age was 13 g/day. The 3% of weight gain velocity during the first year of life was 8 g/day, and this rate did not differ between 0-3 months and 0-12 months of age. Infants with achondroplasia slightly more than doubled their birth weights by 1 year of age in contrast to averaged statured infants who typically triple birth weights by 1 year. Infants with achondroplasia can be thriving but erroneously assessed as failing to thrive if the incorrect reference values are used. This article describes infant weight gain velocity reference data for this population.

Quality of life of children with achondroplasia and their parents - a German cross-sectional study.

BACKGROUND: Achondroplasia is the most common form of disproportionate short stature and might affect not only the quality of life of the affected child but also that of the parents. OBJECTIVES: We aimed to investigate the quality of life of children with achondroplasia from child- and parent perspective as well as the parental quality of life. METHODS: Forty-seven children with achondroplasia and 73 parents from a German patient organization participated. We assessed children's quality of life using the generic Peds QL 4.0™ as self-reports for children aged 8-14 and parent-reports for children aged 4-14 years. Parental quality of life we assessed using the short-form 8-questionnaire. RESULTS: Children with achondroplasia showed significantly lower quality of life scores compared to a healthy reference population from both the child- and parent-report (p = ≤.01), except the child-report of the emotional domain (t (46) = - 1.73, p = .09). Parents reported significantly lower mental health in comparison with a German reference population (t (72) = 5.64, p ≤ .01) but no lower physical health (t (72) = .20, p = .85). While the parental quality of life was a significant predictor of parent-reported children's quality of life (F (6,66) = 2.80, p = .02), it was not for child-reported children's quality of life (F (6,66) = .92, p = .49). CONCLUSIONS: Achondroplasia is chronically debilitating. Thus special efforts are needed to address patients' and parent's quality of life needs. This special health condition may influence the daily life of the entire family because they have to adapt to the child's particular needs. Therefore, clinicians should not only focus on the child's quality of life but also those of the parents.

C-Type Natriuretic Peptide Analogue Therapy in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic disorder that inhibits endochondral ossification, resulting in disproportionate short stature and clinically significant medical complications. Vosoritide is a biologic analogue of C-type natriuretic peptide, a potent stimulator of endochondral ossification. METHODS: In a multinational, phase 2, dose-finding study and extension study, we evaluated the safety and side-effect profile of vosoritide in children (5 to 14 years of age) with achondroplasia. A total of 35 children were enrolled in four sequential cohorts to receive vosoritide at a once-daily subcutaneous dose of 2.5 µg per kilogram of body weight (8 patients in cohort 1), 7.5 µg per kilogram (8 patients in cohort 2), 15.0 µg per kilogram (10 patients in cohort 3), or 30.0 µg per kilogram (9 patients in cohort 4). After 6 months, the dose in cohort 1 was increased to 7.5 µg per kilogram and then to 15.0 µg per kilogram, and in cohort 2, the dose was increased to 15.0 µg per kilogram; the patients in cohorts 3 and 4 continued to receive their initial doses. At the time of data cutoff, the 24-month dose-finding study had been completed, and 30 patients had been enrolled in an ongoing long-term extension study; the median duration of follow-up across both studies was 42 months. RESULTS: During the treatment periods in the dose-finding and extension studies, adverse events occurred in 35 of 35 patients (100%), and serious adverse events occurred in 4 of 35 patients (11%). Therapy was discontinued in 6 patients (in 1 because of an adverse event). During the first 6 months of treatment, a dose-dependent increase in the annualized growth velocity was observed with vosoritide up to a dose of 15.0 µg per kilogram, and a sustained increase in the annualized growth velocity was observed at doses of 15.0 and 30.0 µg per kilogram for up to 42 months. CONCLUSIONS: In children with achondroplasia, once-daily subcutaneous administration of vosoritide was associated with a side-effect profile that appeared generally mild. Treatment resulted in a sustained increase in the annualized growth velocity for up to 42 months. (Funded by BioMarin Pharmaceutical; ClinicalTrials.gov numbers, NCT01603095, NCT02055157, and NCT02724228.).

Thoracic spine Langerhans cell histiocytosis in a child with achondroplasia.

Multifocal bone Langerhans cell histiocytosis (LCH) is usually treated with prednisolone and vinblastine. We present a case conservatively treated with indomethacin with good clinical and radiological response. A 7-year-old achondroplastic boy presented with worsening thoracic back pain and leg weakness. An admission MRI spine showed a pathological T1 vertebrae fracture with posterior soft tissue extension compressing and distorting the spinal cord. A CT guided biopsy revealed an LCH. Steroids were avoided to reduce osteopenia risk and further vertebral fragility. Considering the risk of a thoracic surgical approach in a child with this background, he was managed conservatively with indomethacin and a Sternal Occipital Mandibular Immobilizer (SOMI) Brace. Pain resolved completely within 6 months and the brace was discontinued. Serial follow-up scans showed progressive resolution of the pathological T1 fracture and complete resolution of the spinal cord compression.

Meeting report from the achondroplasia foramen magnum workshop, Salzburg, Austria 22nd June 2019.

A pre-meeting workshop on foramen magnum stenosis in children with achondroplasia was held in Salzburg, Austria at the 9th International Conference on Children's Bone Health (ICCBH) 22-25 June 2019. The screening, monitoring and surgical approach to foramen magnum stenosis still remains controversial with conflicting guidance in the literature. The structure of the workshop consisted of lectures, a debate, expert and delegate discussion and concluded with a research proposal and further next steps. In total, representation by 40 institutions from 22 different countries that care for approximately 1375 children with achondroplasia, were in attendance.

Anthropometrics, diet, and resting energy expenditure in Norwegian adults with achondroplasia.

Individuals with achondroplasia have a high prevalence of obesity and increased risk of cardiovascular disease. Fat distribution, diet, and caloric intake are known risk factors, but the literature concerning diet and energy balance in achondroplasia is limited. The main aim of this study was to describe the anthropometrics, diet, and resting energy expenditure (REE) in a Norwegian adult achondroplasia population. Here, we present a descriptive cross-sectional study with the following variables: anthropometrics, the SmartDiet questionnaire, and dietary records. In addition, REE was measured and estimated using indirect calorimetry and prediction equations. A total of 33 adults with achondroplasia participated with a mean age of 40 years. Mean body mass index was 34.1 kg/m2 , and mean waist circumference was 94.1 cm for men and 82.2 cm for women. Their diets were classified as unhealthy (38%) or in need of improvement (62%). The mean REE values for the total group were 21 kcal/kg for the male (n = 15) and 20 kcal/kg for the female (n = 18). This study revealed a high frequency of central obesity and unhealthy dietary habits in Norwegian adults with achondroplasia. Mean energy intake was low and only 10% higher than the mean REE, and does not explain the high prevalence of abdominal obesity in our population.

TransCon CNP, a Sustained-Release C-Type Natriuretic Peptide Prodrug, a Potentially Safe and Efficacious New Therapeutic Modality for the Treatment of Comorbidities Associated with Fibroblast Growth Factor Receptor 3-Related Skeletal Dysplasias.

TransCon CNP is a C-type natriuretic peptide (CNP-38) conjugated via a cleavable linker to a polyethylene glycol carrier molecule, designed to provide sustained systemic CNP levels upon weekly subcutaneous administration. TransCon CNP is in clinical development for the treatment of comorbidities associated with achondroplasia. In both mice and cynomolgus monkeys, sustained exposure to CNP via TransCon CNP was more efficacious in stimulating bone growth than intermittent CNP exposure. TransCon CNP was well tolerated with no adverse cardiovascular effects observed at exposure levels exceeding the expected clinical therapeutic exposure. At equivalent dose levels, reductions in blood pressure and/or an increase in heart rate were seen following single subcutaneous injections of the unconjugated CNP-38 molecule or a daily CNP-39 molecule (same amino acid sequence as Vosoritide, USAN:INN). The half-life of the daily CNP-39 molecule in cynomolgus monkey was estimated to be 20 minutes, compared with 90 hours for CNP-38, released from TransCon CNP. C max for the CNP-39 molecule (20 µg/kg) was approximately 100-fold higher, compared with the peak CNP level associated with administration of 100 µg/kg CNP as TransCon CNP. Furthermore, CNP exposure for the daily CNP-39 molecule was only evident for up to 2 hours postdose (lower limit of quantification 37 pmol/l), whereas TransCon CNP gave rise to systemic exposure to CNP-38 for at least 7 days postdose. The prolonged CNP exposure and associated hemodynamically safe peak serum concentrations associated with TransCon CNP administration are suggested to improve efficacy, compared with short-lived CNP molecules, due to better therapeutic drug coverage and decreased risk of hypotension. SIGNIFICANCE STATEMENT: The hormone C-type natriuretic peptide (CNP) is in clinical development for the treatment of comorbidities associated with achondroplasia, the most common form of human dwarfism. The TransCon Technology was used to design TransCon CNP, a prodrug that slowly releases active CNP in the body over several days. Preclinical data show great promise for TransCon CNP to be an effective and well-tolerated drug that provides sustained levels of CNP in a convenient once-weekly dose, while avoiding high systemic CNP bolus concentrations that can induce cardiovascular side effects.

Physical, Mental, and Social Problems of Adolescent and Adult Patients with Achondroplasia.

Patients with achondroplasia (ACH) require various medical interventions throughout the lifetime. Survey of health-related quality of life (HRQoL) in adult ACH patients is essential for the evaluation of treatment outcomes performed during childhood such as growth hormone administration and limb lengthening surgeries, but no study focused on the treatment strategy by analyzing HRQoL of ACH patients. The purpose of this study was to assess whether final height impacted on HRQoL and to evaluate what kinds of medical interventions were positively or negatively associated with HRQoL. We included 184 ACH patients (10-67 years old) who were registered in the patients' associations or who had a medical history of the investigators' institutions, and analyzed HRQoL by using Short Form-36 and patient demographics. Physical component summary (PCS) was significantly lower than the standard values in each age, especially in elderly populations, while mental component summary (MCS) was similar to the standard values. Role/social component summary was deteriorated only in elderly populations. The PCS was improved in the patients who had a height of 140 cm or taller (p < 0.001). The PCS and MCS were strongly associated with the past medical history of spine surgeries (p < 0.001 and p = 0.028, respectively). A treatment strategy would be planned to gain a final height of 140 cm or taller during childhood in combination with growth hormone administration and limb lengthening surgeries. Appropriate medical management for neurological complications of adult ACH patients is required to maintain physical and mental function.