Health Supervision for People with Achondroplasia Julie Hoover-Fong, MD, Phd, FACMG,A Charles I

CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care

Health Supervision for People With Achondroplasia Julie Hoover-Fong, MD, PhD, FACMG,a Charles I. Scott, MD, FAAP,b Marilyn C. Jones, MD, FAAP,c COMMITTEE ON GENETICS

Achondroplasia is the most common short-stature skeletal dysplasia, abstract additionally marked by rhizomelia, macrocephaly, midface hypoplasia, and aGreenberg Center for Skeletal Dysplasias, McKusick-Nathans normal cognition. Potential medical complications associated with Department of Genetic Medicine, Johns Hopkins University School of b achondroplasia include lower extremity long bone bowing, middle-ear Medicine, Baltimore, Maryland; Nemours/Alfred I. duPont Hospital for Children and Sidney Kimmel Medical College, Thomas Jefferson dysfunction, obstructive sleep apnea, and, more rarely, cervicomedullary University, Wilmington, Delaware; and cDepartment of Pediatrics, compression, hydrocephalus, thoracolumbar kyphosis, and central sleep University of California, San Diego and Rady Children’s Hospital, San Diego, California apnea. This is the second revision to the original 1995 health supervision guidance from the American Academy of Pediatrics for caring for patients with Drs Hoover-Fong and Scott wrote new content and edited content from the previous AAP statement and responded to reviews; Dr Jones achondroplasia. Although many of the previously published recommendations provided editorial and content review, shepherded the document through multiple stakeholders review, and addressed specific remain appropriate for contemporary medical care, this document highlights concerns; and all authors approved the final manuscript as submitted. interval advancements in the clinical methods available to monitor for Clinical reports from the American Academy of Pediatrics benefit from complications associated with achondroplasia. This document is intended to expertise and resources of liaisons and internal (AAP) and external reviewers. However, clinical reports from the American Academy of provide guidance for health care providers to help identify individual patients Pediatrics may not reflect the views of the liaisons or the at high risk of developing serious sequelae and to enable intervention before organizations or government agencies that they represent. complications develop. The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking into account individual circumstances, may be appropriate.

All clinical reports from the American Academy of Pediatrics automatically expire 5 years after publication unless reaffirmed, The original “Health Supervision for Children with Achondroplasia” policy revised, or retired at or before that time. from the American Academy of Pediatrics (AAP) in 1995 provided useful This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed management recommendations to pediatricians caring for children with conflict of interest statements with the American Academy of achondroplasia from birth through early adulthood.1 The first revision in Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of 2005 expanded the scope of the document to include new information Pediatrics has neither solicited nor accepted any commercial about the molecular genetics of achondroplasia and improvements in involvement in the development of the content of this publication. anticipatory guidance in terms of prevention and treatment of DOI: https://doi.org/10.1542/peds.2020-1010 complications of the condition.2 The majority of the information provided Address correspondence to Julie Hoover-Fong, MD, PhD. E-mail: in those documents remains pertinent and accurate in the current care [email protected] of patients with achondroplasia. This revision highlights additional PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). interval advancements in the clinical methods available to monitor for Copyright © 2020 by the American Academy of Pediatrics complications associated with achondroplasia, including adult health complications that may be rooted in childhood and should, therefore, be monitored and managed from birth. This document also incorporates To cite: Hoover-Fong J, Scott CI, Jones MC, AAP COMMITTEE a few of the more recent treatment options for achondroplasia to provide ON GENETICS. Health Supervision for People With Achondroplasia. Pediatrics. 2020;145(6):e20201010 an informational core from which the general pediatrician can explore

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 145, number 6, June 2020:e20201010 FROM THE AMERICAN ACADEMY OF PEDIATRICS additional resources with patients. mutation in the fibroblast growth to 135 cm (4–4.5 ft) (Fig 1).16 The The authors recognize the audience factor receptor type 3 (FGFR3) gene most common complication, for this document may have variable in that affected individual.3,5,6 occurring in adulthood, is related to medical resources at their disposal to Because virtually all of the causal lumbosacral spinal stenosis with monitor and treat patients with mutations occur at exactly the same compression of the spinal cord or – achondroplasia. The intent of this nucleotide within the gene,6 genetic nerve roots.17 19 This complication is consensus document is to provide testing for achondroplasia is usually treatable by surgical guidance that may be adapted to each straightforward. It is not necessary to decompression, with less sequelae if individual patient in his or her unique perform molecular testing in every treated at an early stage. Most environment. Children and child with a clinical diagnosis of children with achondroplasia do well. adolescents with achondroplasia achondroplasia. However, FGFR3 However, children affected with should have care coordinated through testing should be considered when achondroplasia commonly have a medical home; however, some of a confirmed achondroplasia diagnosis delayed motor milestones the surveillance and counseling is needed. For example, infants or (Fig 2),20–22 otitis media, and bowing suggested in this document will be children with an atypical of the lower legs.23 Less commonly, provided by a number of specialists achondroplasia presentation may infants and children may have serious 7 with expertise in the management of have a second genetic condition. health consequences related to achondroplasia, if these individuals Such children also should be referred craniocervical junction compression are available. for clinical genetics evaluation. because of a relatively small foramen Different mutations in the FGFR3 Achondroplasia is the most common magnum, hydrocephalus, upper- gene can also cause 2 other short condition associated with severe, airway obstruction, or thoracolumbar stature dysplasias: disproportionate short stature, with kyphosis. Although they are less hypochondroplasia and an estimated birth incidence of 1 in common, anticipatory care should thanatophoric dysplasia. A child with 10 000 to 1 in 30 000.3,4 There include identifying children at highest hypochondroplasia has the same is no recognized ethnic or sex risk and intervening to prevent clinical features as one with predisposition. The diagnosis can potentially serious sequelae. Most achondroplasia, as listed above, but usually be made on the basis of individuals with achondroplasia are milder overall. Growth hormone clinical characteristics and specific of normal intelligence and are able to therapy may be considered as features on radiographs, including lead independent and productive a treatment option for those with a square shape of the pelvis with lives.24 Because of their hypochondroplasia, but it has not a small sacrosciatic notch, short disproportionate short stature, been shown to be effective in pedicles of the vertebrae with – however, a number of psychosocial patients with achondroplasia.8 11 interpedicular narrowing from problems can arise.25 Chronic pain, Thanatophoric dysplasia usually can the lower thoracic through lumbar a problem that may begin in be distinguished from achondroplasia region, rhizomelic (proximal) childhood and magnify into and hypochondroplasia because shortening of the long bones, adulthood without intervention, may severe thoracic and lung hypoplasia proximal femoral radiolucency, and be playing a larger role in overall life are expected to be lethal in the pre- or a characteristic chevron shape of the 12 satisfaction and coping than has been early postnatal period in the former. distal femoral epiphyses. Other 26 Rare exceptions of a patient with previously appreciated. Further clinical features include short stature, thanatophoric dysplasia surviving are investigation is needed to better macrocephaly (absolute and relative), reported but only with aggressive understand the temporal relationship trident configuration of the hands, measures of resuscitation at delivery among pain, function, and medical or and long, near-normal-length trunk. and significant respiratory support surgical treatment to allow for the Achondroplasia is an autosomal thereafter.13,14 Age-specific highest quality of life possible. fi dominant disorder, meaning a person recommendations pertaining to Families can bene t from anticipatory with achondroplasia has a 50% genetic counseling and testing are guidance and the opportunity to learn chance of passing the condition on to also included in each age category from other families with children of each of his or her offspring regardless discussed later in this report. disproportionate short stature. The of the sex of the parent or child, consensus-based guidance in this provided the other parent is A great deal is known about the report is designed to help the unaffected. Approximately 75% to natural history of achondroplasia that pediatrician care for children with 80% of patients with achondroplasia can be shared with the family.4,15 achondroplasia and their families. are born to average-stature parents, The average adult height in Issues that need to be addressed at representing a new dominant achondroplasia is approximately 120 various ages are outlined in Table 1.

Downloaded from www.aappublications.org/news by guest on September 26, 2021 2 FROM THE AMERICAN ACADEMY OF PEDIATRICS Similarly, the Little People of America, Inc, the largest US patient support group for short-stature skeletal dysplasia patients and their families, may be a suitable resource for information for medical providers and families (http://www.lpaonline. org/).29

In addition to the age group–speciﬁc guidance presented in this report, 3 topics often arise in early discussions with families about potential treatment of achondroplasia: growth hormone therapy, surgical limb lengthening, and, more recently, drug trials for new medications to alter bone morphology and growth. The following is not meant to be an exhaustive review of these issues but rather a brief foundation on which further discussions can be built.

First, in reference to supplemental growth hormone treatment, there have been longitudinal studies of relatively small groups of patients with achondroplasia treated with growth hormone of various doses and durations.8–11 A recent meta-analysis FIGURE 1 of 12 trials showed a clinically Fifth, 50th, and 95th percentiles for height for children with achondroplasia (solid lines) compared fi – – with height growth curves for the general population (dotted lines), based on 1955 observations insigni cant increase of 5to 4SD from 162 boys and 131 girls with achondroplasia. Adapted from Hoover-Fong JE, Schulze KJ, below the mean when children with McGready J, Barnes H, Scott CI. Age-appropriate body mass index in children with achondroplasia: achondroplasia were treated with – interpretation in relation to indexes of height. Am J Clin Nutr. 2008;88(2):364 371. Curves for the US growth hormone.10 Some authors population are from Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC Growth Charts for the United States: Methods and Development. Hyattsville, MD: National Center for Health Statistics; 2002. Il- also suggest that the rapid (although lustration is from Growth References. Third edition. 2011. Permission for use was granted by the unsustained) linear growth Greenwood Genetic Center. predisposes to worsening scoliosis and kyphosis in these patients.10 In contrast, a few studies have shown a greater adult height in patients with It should be noted that these patients partner with a physician hypochondroplasia treated with suggestions are not appropriate for with special experience and expertise growth hormone therapy.8 As noted other skeletal dysplasia diagnoses concerning skeletal dysplasias, previously, genetic testing would be because each type has its own natural particularly achondroplasia, early in useful to differentiate these 2 fi ’ history, complications, and speci c the child s life. This report provides conditions before embarking on management recommendations. The generally applicable suggestions that a long and expensive course of ’ most recent nosology of genetic must be tailored to a particular child s supplemental growth hormone skeletal disorders includes 436 condition and needs. For reference, treatment. different disorders with primary bone the American Board of Medical manifestations, and more than half of Genetics and Genomics has an online With respect to limb lengthening, these are considered to be skeletal resource to search for a certified there is a body of medical literature dysplasias.27 Because of the vast geneticist throughout the United addressing different surgical methods range of medical considerations for States and in several countries of lengthening, complications of the patients with these diagnoses, it is around the world (http://www.abmg. procedures,30 perspectives on important that pediatricians and their org/pages/searchmem.shtml).28 lengthening the upper extremities,31

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 145, number 6, June 2020 3 child with achondroplasia in one of these trials, it is important to know that a physician conducting a clinical trial should have sufﬁcient experience with the condition to differentiate complications (or a response) to a research pharmaceutical from the natural history of that condition.

THE PRENATAL VISIT Pediatricians may be asked to counsel expectant parents whose fetus has achondroplasia or is suspected to have achondroplasia because of recognition on ultrasonography of disproportionate small stature and relative large head size. In some situations, the pediatrician may be the primary resource for counseling the family. At other times, counseling may already have been provided to the family by a clinical geneticist, FIGURE 2 genetic counselor, or maternal-fetal Developmental screening tests in achondroplasia, based on questionnaire information from 197 medicine specialist. Because of individuals. The bar scale reveals the percentage of children with achondroplasia passing the item. The black triangle on top of the bar reveals the age at which 90% of normal children pass the same a previous relationship with the item. Illustration is from Growth References. Third edition. 2011. Permission for use was granted by family, however, the pediatrician the Greenwood Genetic Center. could be called on to review this information and assist the family in the decision-making process. and reviews of the entire process.32 is made. Finally, this procedure is Opinions about the use and success of associated with complications. The diagnosis of achondroplasia in surgical limb lengthening vary widely. Therefore, it is critical that the the fetus is made most often with Regardless of a patient or family’s surgical team is readily available to certainty when one or both biological position, however, it is important for manage short- and long-term parents have this condition. In this the pediatrician to be aware of a few complications associated with limb circumstance, the parents are usually key issues surrounding surgical limb lengthening. (but not always) knowledgeable lengthening. Limb lengthening is about the disorder, the inheritance, a long and costly process, associated The last novel issue to address is the and the prognosis for the offspring. with significant physical pain for the pharmaceuticals under development However, specific inquiry about the young patient. The age at which this to potentially increase long bone presence of a short stature diagnosis procedure is recommended varies growth and/or ameliorate the skeletal in both parents is recommended among surgeons, but implementation complications of this condition. There when only the mother is present for before epiphyseal closure is the norm, are several compounds currently at the clinical visit and may not with many encouraging various stages of development with spontaneously offer that her partner commencement at younger than different targets and also has short stature. Additionally, it 10 years. Medical decision-making in mechanisms.34,35 More information is important to establish clearly the this age group rests with the parent about these trials can be found online specific short stature diagnosis in or legal representative who could at https://clinicaltrials.gov. The trial both parents. If both parents have make a decision without involving the process often takes several years, and achondroplasia, for example, review child in the discussion. Per AAP policy final approval is required from the US of the potential outcome of this and on informed consent,33 it is highly Food and Drug Administration for each future pregnancy (25% average desired that the child and parents a new drug to become available stature, 50% achondroplasia, 25% engage in discussion about such through a prescription. For families homozygous or “double dominant” elective procedures before a decision contemplating enrollment of their and, therefore, lethal) is

Downloaded from www.aappublications.org/news by guest on September 26, 2021 4 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 1 Health Supervision for People With Achondroplasia Prepregnancy Prenatal and Short- Birth to 1moto1y 1–5y 5–13 y 13–21 y Adult and and 1mo Short-Stature Average-Stature Parents Parents Diagnosis Physical examination X X of fetus X X ———— Imaging X radiographs X ultrasonography of X — ———— fetus Molecular testing X X of fetus X — ——— X Genetic counseling Review natural history X of potential XXXXXXX offspring Recurrence risk and genetics X X XXXXXX Delivery mode and location X X —— ——— X Support group(s), family support X X XXXXXX Desired pregnancy? — XX— ——— X Medical evaluation Growth (height or length, weight, — XXXXXXX occipitofrontal circumference) Physical examination ——XX XXXX Neurologic examination ——XX XXXX Development ——XX XX—— Neuroimaging ——X X if new Xas Xas Xas Xas diagnosis indicated indicated indicated indicated Polysomnography ——X X if new Xas Xas Xas Xas diagnosis indicated indicated indicated indicated Hearing assessment ——XX XXXX Radiography for kyphosis, genu ———XXasXas Xas Xas varus, bowing indicated indicated indicated indicated Anticipation or guidance Warning signs of severe ——XX XXXX complications Car seats — X for hospital XX XX—— discharge Achondroplasia-speciﬁc ——XX X— X — development Jugular bulb dehiscence warning ———XXXXX Supplemental security income ———XXXXX inclusion Accommodations ————XXXX Obesity, exercise, diet ————XXXX Driving ——————XX College ——————XX Job training ——————XX

straightforward. In the situation in as genetic counselors and/or clinical ultrasonographic diagnostic sign for which one parent has achondroplasia geneticists. achondroplasia they named the but the partner has a different “collar hoop” sign, which may be dysplasia diagnosis, the recurrence Most often, the scenario presents evident earlier. If long bone anomalies risk discussion must be tailored to when the diagnosis of achondroplasia and/or disproportion are appreciated is suspected late in gestation on the their speciﬁc diagnoses and earlier in gestation, a skeletal basis of long bone foreshortening associated inheritance. Often, there is dysplasia more severe than incidentally discovered via 37 little medical literature available to ultrasonography in the fetus of an achondroplasia is likely. Higher- reference and anticipate the medical average-stature couple. It is rare for level ultrasonography and course of a compound heterozygous ultrasonographic features of examination for other diagnostic offspring. Ideally, such genetic achondroplasia to be noticeable features are then required. counseling should be provided by before 26 weeks’ gestation, although Conﬁrmation of diagnosis on the genetic medicine professionals, such Boulet et al36 reported a new prenatal basis of ultrasonographic features

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 145, number 6, June 2020 5 characteristic of achondroplasia can couple because of the possibility delivery will be necessary be provided by molecular testing of gonadal mosaicism. because of the characteristic (FGFR3 mutational testing) of 4. Review the natural history and small pelvis and cephalopelvic prenatal specimens (chorionic villus manifestations of disproportion (regardless of – ’ sampling at 11 13 weeks gestation achondroplasia, including whether the fetus is average ’ or amniocentesis after 15 weeks variability.4,15 stature or has achondroplasia gestation). Typically, this would be also and, therefore, 5. Discuss additional studies that performed at a specialized prenatal macrocephaly). Prenatal could be performed in the center. If no such confirmation for consultation with a high-risk newborn period to confirm the achondroplasia (or any other maternal or fetal medicine diagnosis (eg, blood test for dysplasia) has been completed, specialist is recommended to mutation in FGFR3, radiographs caution should be exercised when investigate whether general to review for achondroplasia- counseling the family. anesthesia or spinal or epidural specific features). If miscarriage, anesthesia will be needed for stillbirth, or termination occurs, Prenatal consultation involving delivery. In an average-stature confirmatory testing is important acoupleinwhichoneorbothcarry pregnant woman carrying a fetus if the woman or family desires a skeletal dysplasia diagnosis and are with achondroplasia, a cesarean optimal genetic counseling. If seeking genetic counseling and delivery may also, but not always, specific molecular testing cannot anticipatory guidance is best arranged be necessary because of fetal 38 be offered immediately, try to before pregnancy. Typically, this visit macrocephaly. would be with a medical geneticist or secure a blood or tissue sample 9. Establish where the infant with genetic counselor. In this scenario, for future testing. the suspected (or possible) there is ample time to confirm the 6. Review currently available skeletal dysplasia diagnosis will parental dysplasia diagnoses and treatments and interventions, be delivered. Pediatric services to evaluate the woman (if she is short including efficacy, complications, manage potential medical stature) for neuraxial complications or adverse effects, costs, and other complications at or shortly after previous surgical procedures, which burdens of these treatments. delivery may be necessary and could influence anesthesia options for Discuss possible future are not available at all hospitals. delivery (ie, general versus spinal or treatments and interventions. 10. When both parents are of epidural). Please see the medical evaluation disproportionate short stature, and anticipatory guidance assess the possibility of the fetus discussions in the sections Depending on the prenatal situation, inheriting both conditions. on health supervision for the pediatrician may consider the Infants with homozygous children ages 1 month to following steps as needed: achondroplasia usually are 1 year, 1 to 5 years, and 5 to 1. Review, confirm, and stillborn or die shortly after demonstrate laboratory or 13 years. birth.40 imaging studies leading to the 7. Explore the options available to 11. Be aware that many of these diagnosis. the family for the management discussions will be coordinated 2. Explain the mechanisms for and rearing of the child by using with the prenatal team, including occurrence of achondroplasia in a nondirective approach. In cases a medical geneticist, genetic the fetus and the recurrence risk of early prenatal diagnosis, these counselor, and/or maternal- for the family, depending on the options may include discussion fetal medicine specialist. The presence of a dysplasia in both, of pregnancy termination, importance of one, or neither of the parents. continuation of pregnancy and a knowledgeable medical home rearing of the child at home, 3. Explain that up to 80% of for the expected infant should be foster care, or adoption. If patients with achondroplasia are reviewed. born to average-stature parents. adoption is planned, the Little People of America, Inc, has In these affected children, their HEALTH SUPERVISION FROM BIRTH TO achondroplasia occurred because adoption resources available 1 MONTH OF AGE: NEWBORN INFANTS of a spontaneous mutation in the (http://www.lpaonline.org/ 39 FGFR3 gene. In this situation, adoption). Diagnosis, Genetic Counseling recurrence risk is empirically 8. If the pregnant woman carries 1. Confirm the diagnosis by approximately 1% for future the diagnosis of achondroplasia, radiographic studies in the pregnancies for this specific inform her that a cesarean newborn period. External physical

Downloaded from www.aappublications.org/news by guest on September 26, 2021 6 FROM THE AMERICAN ACADEMY OF PEDIATRICS features may not be highly obvious a. Refer the family to a support and axial and for achondroplasia. Radiographs group, such as Little People of appendicular tone. 39 should include anteroposterior America. b. Polysomnography (overnight and lateral skull, anteroposterior b. If parents do not wish to join sleep study, evaluated by and lateral cervical spine, a group, offer meeting a pediatric pulmonologist, anteroposterior and lateral chest individually with other affected including end tidal carbon and abdomen with pelvis and individuals or parents. dioxide in addition to standard upper femurs, c. Discuss how they will tell their measures of apnea, hypopnea, anteroposterior of each upper and family and friends about their saturation) to assess for lower extremity long bone, and child’s diagnosis. unusual central apnea. anteroposterior of hands and feet d. Refer to other support c. Neuroimaging, provided it can separate from long bones. resources, such as clergy, social be performed safely by Molecular studies may be pursued workers, and psychologists. appropriate medical personnel if sedation or anesthesia is if desired. e. Remind parents that most required to obtain images. If 2. Discuss genetics of achondroplasia people with achondroplasia abnormalities suggestive of with the parents, including the lead productive, craniocervical compromise are independent lives. following: detected in the medical history, a. Autosomal dominant f. Supply the parents with neurologic examination, or inheritance: Any person with educational books and sleep study, then neuroimaging achondroplasia will have a 50% pamphlets (http://www. is indicated. Neuroimaging 29 chance of passing this condition lpaonline.org/). should not be used in isolation on to each offspring, regardless g. Discuss the realistic functional to determine when or whether of the sex of the parent difficulties for affected surgery is indicated. and child. individuals. 4. Consider the pros and cons of the b. Approximately 80% of children neuroimaging options: born with achondroplasia a. Computed tomography with represent spontaneous new Medical Evaluation thin cuts and bone windows: mutations in the FGFR3 gene. 1. Measure and plot total body i. Can compare foramen c. Germ-line mosaicism (in which length, weight, and occipitofrontal magnum size with some germ cells are derived circumference on achondroplasia- published achondroplasia fi from a normal cell line and speci c growth charts (Figs 1 and norms.46,47 3–5)16,22,44 at birth and every some are from a cell line with ii. May be possible without health supervision visit. Review a mutation, also known as sedation. gonadal mosaicism) has been these growth parameters with iii. Does not provide adequate reported in families with both parents. images of brainstem and achondroplasia. This means 2. Use achondroplasia-specific upper cervical cord to that 2 average-stature parents developmental charts at every determine if there is neural have had more than 1 child health supervision visit compromise, signaling with achondroplasia (Fig 2).20,22 change. attributable to gonadal 3. Assess every infant with b. MRI: mosaicism. The recurrence risk achondroplasia for craniocervical of achondroplasia in sporadic junction risks as soon as the i. Provides direct assessment cases via gonadal mosaicism is diagnosis is recognized45 via the of the brainstem and upper 41–43 approximately 1%. following: cervical spinal cord, but no d. Recurrence risk when both a. Careful neurologic history and standards for estimation of parents have a skeletal examination. This includes foraminal size by MRI are dysplasia diagnosis should also inquiry about feeding ability, currently available. be reviewed. choking or gagging with ii. May require general 3. Recognize the potential feeding, prolonged apnea while anesthesia if fast MRI psychosocial implications for both sleeping, cyanosis of lips or protocol is not used or parent and child related to short mouth with feeding or sleeping, available. General stature. symmetry of limb movements, anesthesia should only be

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 145, number 6, June 2020 7 performed in a clinical 6. Establish care with a pediatric d. Restrictive pulmonary disease setting in which a pediatric orthopedist to monitor the spine. occurs in less than 5% of anesthesiologist, nurse 7. Confirm newborn screening children with achondroplasia anesthetist, or other airway hearing result and follow-up failed who are younger than 55 specialist is present to screening results with formal 3 years. Living at high manage the procedure. audiology assessment. elevation may exacerbate Often, a newborn infant can pulmonary complications as in be wrapped and scanned Anticipatory Guidance average-stature individuals. while asleep without 1. Discuss the following possible Obstructive pulmonary sedation or anesthesia, severe medical complications and disease is much particularly when a faster methods of prevention: more common and magnetic resonance scanner warrants systematic a. Unexpected infant death is available. assessment.15,56,57 occurs in 2% to 5% of all iii. Evidence that flexion or infants with 2. Be aware that most infants with extension of the cervical achondroplasia50,51 if achondroplasia develop spine during MRI may aggressive, early assessments thoracolumbar kyphosis. More reveal dynamic cord are not pursued to detect severe kyphosis is associated compression and alteration central apnea resulting from with unsupported sitting before of cerebrospinal fluid (CSF) compression of the brainstem there is adequate trunk muscle flow in achondroplasia, and arteries at the level of the strength and tone.58,59 Borkhuu which is a better indicator foramen magnum. et al60 observed developmental of the need for surgical delays in motor skill intervention.48,49 b. The universally small foramen magnum may result in a high acquisition (compared with other 5. Refer in a timely manner to cervical myelopathy,52,53 also children with achondroplasia) to experienced neurosurgical detectable by the be highly associated with specialist if any of the following aforementioned early progression of thoracolumbar are detected during the assessments. kyphosis.61 aforementioned craniocervical junction assessment: c. Macrocephaly with excessive a. Back support should be extra-axial fluid and provided during bottle and/or a. Abnormal neurologic asymptomatic breastfeeding. examination marked by ventriculomegaly is a normal “fl ” b. Unsupported sitting and hypotonia or oppiness, feature of achondroplasia54 weakness, sustained lower devices that cause curved but may be complicated by “ ” extremity clonus, asymmetric sitting or C sitting, such as hydrocephalus. “ ” reflexes, or choking or gagging umbrella-style strollers and i. Should head circumference with eating. soft canvas seats, should be increase unexpectedly on avoided during the first year b. Poor weight gain on an achondroplasia-specific fi of life. achondroplasia-speci c growth curve, the fontanelle bulge c. Care with a pediatric charts, especially if caloric or become hard to orthopedist should be intake and/or infant feeding is palpation, or lethargy, fi established to monitor suf cient. irritability, poor weight c. Sleep study showing hypoxemic gain, or marked the spine. episodes with oxygen developmental delay occur, 3. Be aware that the common saturation ,85% and/or the imaging and potential complication of spinal stenosis central apnea beyond that referral to a neurosurgical rarely occurs in childhood but expected in an average-stature, specialist is indicated. manifests in older individuals 50 healthy newborn infant. ii. Benign extra-axial fluid and with numbness, weakness, and 52 d. Imaging showing marked asymptomatic altered deep tendon reflexes. smaller foramen magnum size, ventriculomegaly Severe thoracolumbar kyphosis substantial deformation of the visualized by MRI should can greatly exacerbate spinal upper cervical spinal cord, or not be misinterpreted as stenosis; thus, the lack of CSF around the indicative of need for shunt recommendation is to avoid spinal cord. placement. unsupported sitting before there

Downloaded from www.aappublications.org/news by guest on September 26, 2021 8 FROM THE AMERICAN ACADEMY OF PEDIATRICS FIGURE 3 Fifth, 50th, and 95th percentiles for weight for boys (top) and girls (bottom) 0 to 36 months of age with achondroplasia (solid lines) compared with those of the general population (dotted lines), based on 1853 observations from 155 boys and 128 girls with achondroplasia. Adapted from Hoover-Fong JE, Schulze KJ, McGready J, Barnes H, Scott CI. Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height. Am J Clin Nutr. 2008;88(2):364–371. Curves for the US population are from Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC Growth Charts for the United States: Methods and Development. Hyattsville, MD: National Center for Health Statistics; 2002. Illustration is from Growth References. Third edition. 2011. Permission for use was granted by the Greenwood Genetic Center.

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 145, number 6, June 2020 9 FIGURE 4 Fifth, 50th, and 95th percentiles for weight for boys (top) and girls (bottom) 2 to 16 years of age with achondroplasia (solid lines) compared with thoseof the general population (dotted lines), based on 1853 observations from 155 boys and 128 girls with achondroplasia. Adapted from Hoover-Fong JE, Schulze KJ, McGready J, Barnes H, Scott CI. Age-appropriate body mass index in children with achondroplasia: interpretation in relation to indexes of height. Am J Clin Nutr. 2008;88(2):364–371. Curves for the US population are from Kuczmarski RJ, Ogden CL, Guo SS, et al. 2000 CDC Growth Charts for the United States: Methods and Development. Hyattsville, MD: National Center for Health Statistics; 2002. Illustration is from Growth References. Third edition. 2011. Permission for use was granted by the Greenwood Genetic Center.

Downloaded from www.aappublications.org/news by guest on September 26, 2021 10 FROM THE AMERICAN ACADEMY OF PEDIATRICS FIGURE 5 Head circumference curves (mean 6 2 SD) for children with achondroplasia (solid lines) compared with those for the general population (dashed lines). Data are derived from 114 boys and 145 girls. Graphs are adapted from Horton WA, Rotter JI, Rimoin DL, Scott CI, Hall JG. Standard growth curves for achondroplasia. J Pediatr. 1978;93(3):435–438. General population curves are from Rollins JD, Collins JS, Holden KR. United States head circumference growth reference charts: birth to 21 years. J Pediatr. 2010;156(6):907–913.e2. Illustration is from Growth References. Third edition. 2011. Permission for use was granted by the Greenwood Genetic Center.

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 145, number 6, June 2020 11 is adequate trunk muscle cause for this, but serious intubation) could lead to strength and tone. problems may occur during unintentional spinal cord 4. Advise parents to use an infant infancy (eg, cervicomedullary compression secondary to seat or infant carrier that has compression, central sleep constriction of the foramen a firm back (not excessive apnea), as noted. magnum. padding) to support the neck and 8. Inform parents that growth b. Medication should be dosed to use a rear-facing car safety hormone and vitamin for patient size, not age. seat for as long as possible. supplements are not effective in c. Venous access may be more fi a. Car seat laws vary by state signi cantly increasing stature. difficult because of incomplete (and country) as to the age, Growth hormone may cause elbow extension. weight, and/or height of a temporary increase in growth d. In general, spinal or epidural a child required to convert velocity, but little to no anesthesia should be avoided fi their seat to forward-facing. signi cant increase in end height unless neuroimaging reveals 8–11 Inquire with local experts (eg, has been shown. adequate space inside the police, hospital, or fire station 9. Discuss the availability of spinal canal and there are no where car seat installation extended limb lengthening signs of neurologic clinics are offered) or online using a variety of surgical compromise. motor vehicle administration. techniques, which can b. Infants should not sleep result in an increase in HEALTH SUPERVISION FROM 1 MONTH unattended in car seats; this is ultimate height. TO 1 YEAR OF AGE: INFANCY especially important in those a. This is a long process with Diagnosis, Genetic Counseling with achondroplasia because high cost and associated decreased axial tone and physical pain and can have 1. For infants not diagnosed in the strength in combination with postoperative adverse effects. newborn period, confirm diagnosis the large head creates great b. If a family undertakes this by radiographs and risk of craniocervical and procedure, it is critical that the physical examination and fi airway compromise. affected child and parents offer molecular con rmation, if desired. 5. Avoid use of products like have discussed this at great mechanical swings and carrying length and that they are in 2. Inquire about personal support slings to limit uncontrolled head agreement that proceeding available to the family. movement around the small with this surgery is the 3. Inquire about contact with foramen magnum. There is a risk appropriate decision for them. support groups. of death if the cervicomedullary c. If pursued, it should be 4. Observe the emotional status of junction is compromised, even in completed at a well- parents and intrafamily infants in which there were no established surgical center relationships. signs of abnormal neurologic with experience and the 5. Discuss the importance of normal status. Always support the head capability to manage these socializing experiences with other and neck with the caregiver’s patients long-term for children. hand, minimizing flexion and complications. 6. Ask the parents whether they have extension (also known as head fi 10. Inform parents that the nal educated their family members bobbling). expected adult height for people about achondroplasia and offer 6. Advise parents that normal with achondroplasia is resources to the Little People of intelligence is expected. approximately 120 to 135 cm America or local genetic 7. Advise parents that overall, (4–4.5 ft). counselors; discuss sibling people with achondroplasia have 11. If an individual with adjustment. fairly normal life expectancy. achondroplasia requires 7. Review genetics of achondroplasia However, the following should be anesthesia and surgery, consider as outlined in the Birth to 1 Month noted: the following63: section, as needed. 61 a. Wynn et al demonstrated a. Care should be taken in 62 10-year earlier mortality. manipulation of the neck Medical Evaluation b. Longitudinal studies are because uncontrolled neck 1. Assess growth (length, weight, required to determine the movement (as may occur with head circumference) and

Downloaded from www.aappublications.org/news by guest on September 26, 2021 12 FROM THE AMERICAN ACADEMY OF PEDIATRICS development only in comparison f. Imaging showing marked short eustachian tubes. Indicate with children with achondroplasia smaller foramen magnum size, that an ear examination is (Figs 1–5). substantial deformation of the appropriate with any persistent or 2. Perform physical examination, upper cervical spinal cord, or severe upper respiratory including neurologic examination. lack of CSF around spinal cord. tract infection or when parents suspect that ear pain may be 3. Check motor development and 6. Check for serous otitis media. present. discuss development; note on the Formal behavioral audiometric milestone charts for assessment should be completed 3. Recommend annual audiology achondroplasia.20,22 Expect motor by 9 to 12 months of age and assessment as part of routine delay as compared with average- managed as part of routine health health care for patients with 62,64 stature, age-matched children but care for patients with achondroplasia. not social or cognitive delay. achondroplasia, ideally on an 4. There is a risk of jugular bulb annual basis.62,64 Language delay 4. For infants not diagnosed in the dehiscence (absence of the may be present secondary to “ ” newborn period, arrange for temporal bone roof over the conductive hearing loss. polysomnography and jugular bulb) in patients with neuroimaging at the time of 7. Continue to monitor for achondroplasia. This diagnosis. progression of kyphosis at the malformation predisposes to thoracolumbar junction. accidental puncture of the jugular 5. Refer the infant to a pediatric bulb during tympanostomy tube neurologist or pediatric a. Parents and therapists (if used) placement.65 neurosurgeon if any of the should be instructed to provide fi following are present: back support during the rst 5. Avoid infant carriers and seated year of life. positions that “curl up” the infant a. Head circumference b. Avoid unsupported sitting and or young child and avoid disproportionately large for devices that cause curved prolonged unsupported sitting. length and weight on sitting or “C sitting,” such as 6. Advise parents to use an infant achondroplasia-specific curves “umbrella-style” strollers and seat or infant carrier that has or head circumference crossing soft canvas seats, during the a firm back (reduced padding) to percentiles. first year of life. support the neck and to use a rear- b. Fontanelle bulging or becoming c. Position the infant for feeding facing car safety seat for as long as hard to palpation. with a straight back and head possible. c. Abnormal neurologic and neck in alignment, a. Car seat laws vary by state (and examination marked by supported by firm pillows; country), so inquiry with local “fl ” hypotonia or oppiness, a feeder seat may be a good experts (eg, police, hospital, or lethargy, irritability, weakness, option. fire station where car seat sustained lower extremity d. Mild, mobile (nonfixed) installation clinics are offered) clonus, asymmetric reflexes, thoracolumbar kyphosis will or online motor vehicle choking or gagging with eating, often improve or resolve when administration is or early hand preference, which the child begins to walk. recommended. may be attributable to e. If severe kyphosis appears to b. Infants should not sleep hydrocephalus or be developing, seek pediatric unattended in car seats; this is craniocervical junction orthopedic assessment to especially important in those compromise. determine if bracing is needed. with achondroplasia because d. Poor weight gain on Rarely, surgical intervention decreased axial tone and fi achondroplasia-speci c growth may be necessary.59,60 strength in combination with charts, especially if caloric the large head creates great risk intake is sufficient. of craniocervical and airway Anticipatory Guidance e. Polysomnography showing compromise. hypoxemic episodes with 1. Discuss early-intervention services 7. Be aware that external rotation of oxygen saturation lower than if needed. This is not a uniform the hips is commonly present and 85% and/or central apnea recommendation simply because usually disappears spontaneously beyond that expected in an of the diagnosis of achondroplasia. when the child begins to bear average-stature, healthy 2. Review the increased risk of weight. This finding does not infant.50 serous otitis media because of require bracing for the infant.

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 145, number 6, June 2020 13 8. Discuss the option of instability of the soft tissues complications.67 In addition to filing for Supplemental surrounding the knee and usual treatments for Security Income benefits as internal tibial torsion. If gastroesophageal reflux disease, appropriate. positional deformity and consider referral to a pediatric instability leads to difficulty gastroenterologist or pulmonologist. HEALTH SUPERVISION FROM 1 YEAR TO walking, a thrust at the knee 5 YEARS: EARLY CHILDHOOD (uncontrolled lateral or 12. Do not misinterpret greater-than- medial movement with average sweating as indicative of Diagnosis, Genetic Counseling weight bearing), or chronic serious medical problems; it is 1. Review genetics of achondroplasia pain, consult a pediatric normal in many children with as outlined in the Birth to 1 Month orthopedist. achondroplasia, particularly section, as needed. 7. Check the child’s hips for hip while sleeping. But if there is 2. Inquire about contact with flexion contractures. Refer to sweating with eating or the support groups. physical therapy or pediatric sweating increases dramatically orthopedics for exercise while sleeping and airway Medical Evaluation recommendation to decrease obstruction is observed, consider fl further evaluation with 1. Assess growth (length or height, lumbar lordosis and hip exion a sleep study. weight, head circumference) and contractures if indicated. development in comparison only Stretching of the hip is performed 13. In rare instances in which with children with gently so as not to cause diagnosis of achondroplasia is achondroplasia (Figs 1–5). subluxation. delayed beyond 1 year of age, arrange for polysomnography for 2. Assess BMI on achondroplasia- 8. Ensure that the patient has an all individuals and neuroimaging specific charts66 in accordance audiology assessment every year on the basis of clinical signs and with AAP recommendations to in conjunction with symptoms concerning for measure BMI. establishment of care with an 62,64 craniocervical compression, as otolaryngologist. 3. Perform physical examination, discussed previously. including neurologic 9. Ensure that the patient has examination. a speech evaluation at no later Anticipatory Guidance 4. Check motor development and than 2 years of age. If speech is discuss development; note on the delayed, conductive 1. Consider adapting the home so milestone charts for hearing loss attributable to that the child can become achondroplasia.20,22 Expect chronic serous otitis media independent (eg, lower the light motor delay as compared with should be excluded. switches, use lever door handles average-stature, age-matched 10. Because most children with and lever sink faucets, make the children but not social or achondroplasia snore, monitor toilet accessible, and supply step cognitive delay. closely for signs of obstructive stools). Determine if an occupational therapy 5. Continue to monitor for sleep apnea (increased consultation is needed to help thoracolumbar kyphosis. Any retraction, glottal stops, choking, adapt the home. kyphosis present should resolve intermittent breathing, apnea, as the child begins to bear deep compensatory sighs, 2. Discuss adapting age-appropriate weight. Lumbar lordosis usually secondary enuresis, recurrent clothing with snapless, easy- develops but rarely requires nighttime awakening or opening fasteners and tuckable specific intervention. Weight emesis) is recommended. If loops because children with bearing and walking may occur obstructive sleep apnea is achondroplasia have smaller fi late; however, they are suspected, then pulmonary ngers and shorter arms. expected by 2 to 2.5 years of consultation and Determine if an occupational age. When weight bearing polysomnography are indicated. therapy consultation is needed. begins, the external rotation of 11. Be aware that gastroesophageal 3. Discuss adaptation of toys, such the hips should self-correct to reflux disease may be more as tricycles, to accommodate a normal orientation within 6 common in children with short limbs. months. achondroplasia and may be more 4. Discuss adaptation of toilets to 6. Anticipate some bowing of the common in those with allow comfortable, independent legs. Many children will also have neurorespiratory use. An extended wand for

Downloaded from www.aappublications.org/news by guest on September 26, 2021 14 FROM THE AMERICAN ACADEMY OF PEDIATRICS wiping is rarely needed in this HEALTH SUPERVISION FROM 5 TO the school to cope with heavy age group, provided surgical 13 YEARS: LATE CHILDHOOD doors, high doorknobs, reaching spinal fusion has not been for the blackboard, foot support, Diagnosis, Genetic Counseling performed. Discuss and a regular-sized desk. Also, be toileting at school and special 1. Review genetics of achondroplasia sure that the child can use the preparations needed by the as outlined in the Birth to 1 Month restroom independently. school because of the child’s section, as needed. 3. Prepare the child for the short stature. 2. Inquire about contact with questions and curiosity of others. 5. Discuss the use of a stool during support groups. They are 4. Assure the parents that children sitting so that the child’s feet are especially useful at this age. with achondroplasia usually are not hanging. Feet need support Medical Evaluation included in the regular education while the child is sitting at a desk, program. 1. Assess growth (height, weight, in a chair, or on the toilet. A 5. Counsel parents to use a child head circumference) and cushion behind the child’s back safety seat with a full harness to development in comparison only may be required for good posture the highest weight allowed by the with children with achondroplasia and to prevent chronic back pain. manufacturer of the seat and (Figs 1–5). 6. Counsel parents for optimal then to transition to the belt- 2. Review weight control.44,66 protection to use a convertible positioning booster seat for Encouraging and maintaining rear-facing car safety seat to the optimal seatbelt positioning. physical activity with dietary intake is highest weight and height 6. Review socialization and foster important. allowed by the manufacturer of independence. 68 3. Complete a general and the seat. A rear-facing seat 7. Maintain orthopedic surveillance neurologically oriented physical provides the best support every 1 to 2 years or sooner, if examination. protection and positioning angle problems occur. 4. Check deep tendon reflexes yearly for a child with macrocephaly 8. Emphasize supported sitting in for asymmetry or increased reflexes and skeletal dysplasia. school desks and while doing that suggest spinal stenosis. 7. Review weight control and eating homework to avoid kyphosis. 5. Continue to assess history for habits to avoid obesity, which 9. Develop an activity program with possible obstructive sleep apnea often becomes a problem in mid acceptable activities, such as (increased retraction, glottal stops, to late childhood and through swimming and biking. The child choking, intermittent breathing, adulthood. should avoid competitive apnea, deep compensatory sighs, 8. Discuss orthodontic bracing and gymnastics and collision sports secondary enuresis, recurrent the potential need for palatal because of the potential for nighttime awakening or emesis). If neurologic complications expansion in the future. obstructive sleep apnea is secondary to cervical spinal 9. Encourage all physical activities suspected, then pulmonary stenosis. in which the child can participate consultation and safely. All children should avoid polysomnography are indicated. 10. Review orthodontic and speech 69 status. trampolines and high-impact, 6. Ensure that formal hearing body-contact, and collision assessment is conducted as part of 70 sports. annual health maintenance for 62,64 HEALTH SUPERVISION FROM 13 TO 10. Discuss how to talk with the child patients with achondroplasia, 21 YEARS OR OLDER: ADOLESCENCE TO and friends or family members with ear, nose, and throat follow- EARLY ADULTHOOD about short stature. up should problems be identified. 11. Encourage preschool attendance 7. Assess for pain and its effects on Diagnosis, Genetic Counseling so that the child can learn to activities of daily living and 1. Discuss the diagnosis with the socialize in an age-appropriate desired physical activity.26 adolescent to be sure that he or way, and work with parents to she has the vocabulary and the Anticipatory Guidance prepare the teacher and the other understanding of the genetic children so that the child is 1. Determine school readiness. nature of achondroplasia. treated in an age-appropriate 2. Discuss preparation of the school 2. Discuss contraception. People with manner (ie, not dictated by the and teacher for a child with short achondroplasia usually are fertile. child’s height). stature. Suggest adaptive aids for The importance and use of

Downloaded from www.aappublications.org/news by guest on September 26, 2021 PEDIATRICS Volume 145, number 6, June 2020 15 contraception should be discussed health care for patients with symptomatology of the patient. with both male and female achondroplasia, ideally on an Several of the key features that adolescents with achondroplasia, annual basis. should be addressed in adulthood are just as it should be for average- 6. Assess for pain and its effects on included in the Prenatal Visit section stature adolescents. Tailored to the activities of daily living and for short-stature adults and noted in maturity and sexual activity of the desired physical activity. Table 1. adolescent or young adult, review recurrence risk counseling with the Anticipatory Guidance LEAD AUTHORS patient, as outlined in the Prenatal Julie Hoover-Fong, MD, PhD, FACMG 1. Check on social adaptation. Foster Visit section previously. The parents Charles I. Scott, MD, FAAP independence. of adolescents or young adults may Marilyn C. Jones, MD, FAAP have heard this information for their 2. Review orthodontic status. recurrence risk counseling; now the 3. Continue weight counseling. COUNCIL ON GENETICS EXECUTIVE – adolescent needs this information 4. Encourage the family and affected COMMITTEE, 2017 2018 forhisorherreproductivedecision- patient to set career and life goals Emily Chen, MD, PhD, FAAP, Co-Chairperson making. Ideally, discussions about high and appropriate, as for other Tracy L. Trotter, MD, FAAP, Co-Chairperson Susan A. Berry, MD, FAAP prenatal testing, pregnancy, and members of the family. delivery are conducted before Leah W. Burke, MD, FAAP 5. Discuss college, vocational Timothy A. Geleske, MD, FAAP conception occurs.38 planning and training, and other Rizwan Hamid, MD, PhD, FAAP 3. Continue to encourage plans after high school. Robert J. Hopkin, MD, FAAP participation in social activities and Wendy J. Introne, MD, FAAP 6. Discuss driving. A driver’s license Michael J. Lyons, MD, FAAP support groups. It is particularly is obtainable. Drivers usually Angela Scheuerle, MD, FAAP useful during this age period. require a vehicle that is adapted Joan M. Stoler, MD, FAAP 4. Per the published AAP guidelines with pedal extenders; extenders for adolescent health, proceed that can be easily mounted and FORMER EXECUTIVE COMMITTEE MEMBERS with discussions regarding removed as needed are available. Robert A. Saul, MD, FAAP, Chairperson smoking, drug use, alcohol use, Consultation with a local driver Debra L. Freedenberg, MD, FAAP sexual activity, gender identity, rehabilitation specialist or the Marilyn C. Jones, MD, FAAP exposure to weapons, food and Association for Driver Beth Anne Tarini, MD, MS, FAAP shelter security, and a focus on Rehabilitation Specialists (http:// bullying and psychological health. www.aded.net/; phone 866-672- LIAISONS 9466) may be helpful if vehicle Katrina M. Dipple, MD, PhD – American modifications are needed. College of Medical Genetics Medical Evaluation Individuals who want to have an Melissa A. Parisi, MD, PhD – Eunice Kennedy air bag on-off switch must read an Shriver National Institute of Child Health and 1. Continue to record growth Human Development parameters. informational brochure and Britton D. Rink, MD – American College of submit an official request to the 2. Review weight control and diet. Obstetricians and Gynecologists National Highway Traffic Safety Joan A. Scott, MS, CGC – Health Resources and Encouraging and maintaining Administration (1-888-327-4236; Services Administration, Maternal and Child physical activity with dietary www.nhtsa.gov). Health Bureau intake is necessary. Stuart K. Shapira, MD, PhD – Centers for 7. Assist in transition to adult 3. Complete a general and Disease Control and Prevention health care. neurologically oriented physical examination. Monitor for any signs STAFF or symptoms of nerve HEALTH SUPERVISION FOR ADULTS Paul Spire compression and check deep WITH ACHONDROPLASIA tendon reflexes, tone, and sensory Health supervision for adults with findings. achondroplasia, which includes ABBREVIATIONS 4. Continue to assess for possible genetic counseling, medical concerns AAP: American Academy of obstructive sleep apnea and obtain and surveillance, and anticipatory Pediatrics polysomnography on the basis of guidance, is multifaceted. Health CSF: cerebrospinal fluid symptoms. supervision requires specific FGFR3: fibroblast growth factor 5. Formal hearing assessment is management recommendations based receptor type 3 recommended as part of routine on the scope of the disease and

Downloaded from www.aappublications.org/news by guest on September 26, 2021 16 FROM THE AMERICAN ACADEMY OF PEDIATRICS FINANCIAL DISCLOSURE: Dr Hoover-Fong received research support from Alexion and BioMarin, participated on Alexion’s advisory board (not related to achondroplasia), and has a consultancy and educational relationship with BioMarin (related to achondroplasia); and Drs Scott and Jones have indicated they have no ﬁnancial relationships relevant to this article to disclose. FUNDING: No external funding. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conﬂicts of interest to disclose.

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