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1 AMERICAN ACADEMY OF PEDIATRICS . CLINICAL REPORT. Guidance for the Clinician in Rendering pediatric Care Tracy L. Trotter, MD; Judith G. Hall, OC, MD; and the Committee on Genetics Health Supervision for Children With Achondroplasia ABSTRACT. Achondroplasia is the most common con- radiographs, which include contracted base of the dition associated with disproportionate short stature. skull, square shape of the pelvis with a small sacro- Substantial information is available concerning the nat- sciatic notch, short pedicles of the vertebrae, rhi- ural history and anticipatory health supervision needs in zomelic (proximal) shortening of the long bones, tri- children with this dwarfing disorder. Most children with dent hands, a normal-length trunk, proximal femoral achondroplasia have delayed motor milestones, prob- lems with persistent or recurrent middle-ear dysfunction, radiolucency, and (by midchildhood) a characteristic and bowing of the lower legs.

2 Less often, infants and chevron shape of the distal femoral epiphysis. Other children may have serious health consequences related to rhizomelic dwarfing disorders such as hypochondro- hydrocephalus, craniocervical junction compression, up- plasia and thanatophoric dysplasia are part of the per-airway obstruction, or thoracolumbar kyphosis. An- differential diagnosis, but achondroplasia usually ticipatory care should be directed at identifying children can be distinguished from them because the changes who are at high risk and intervening to prevent serious in hypochondroplasia are milder and the changes in sequelae. This report is designed to help the pediatrician thanatophoric dysplasia are much more severe and care for children with achondroplasia and their families. invariably lethal. Achondroplasia is an autosomal PEDIATRICS 2005;116:771 783; achondroplasia, short stat- ure, children, health supervision. dominant disorder, but approximately 75% of cases represent new dominant mutations.

3 Achondroplasia is caused by mutation in the gene that codes for the ABBREVIATIONS. OFC, occipital-frontal circumference; CT, com- fibroblast growth factor receptor type 3 (FGFR3).5 7. puted tomography. Because virtually all of the causal mutations occur at exactly the same place within the gene,7 molecular INTRODUCTION. testing is straightforward. It is not necessary to per- T. his clinical report is designed to assist the pe- form molecular testing in every child with a clinical diatrician in caring for children with achondro- diagnosis of achondroplasia. However, FGFR3 test- plasia confirmed by radiographs and physical ing should be performed in children who are in any features. Although pediatricians usually first see way atypical or in circumstances in which differen- children with achondroplasia during infancy, occa- tiation from similar disorders, such as hypochondro- sionally they are called on to advise a pregnant plasia, is not certain.

4 Such children also should be woman who has been informed of the prenatal di- referred for clinical genetic evaluation. agnosis of achondroplasia or asked to examine a A great deal is known about the natural history of newborn to help establish the diagnosis. Therefore, achondroplasia that can be shared with the ,8. this report offers advice for these situations as well. The average adult height in achondroplasia is ap- Substantial new information has appeared since proximately 4 ft for men and women (Figs 1 and 2).9. publication of the first policy statement on health The most common complication, occurring in adult- supervision of children with In par- hood, is related to lumbosacral spinal stenosis with ticular, a great deal has been learned about the mo- compression of the spinal cord or nerve ,11. lecular genetics of the In addition, a more This complication is usually treatable by surgical complete understanding of how certain serious com- decompression if it is diagnosed at an early stage.

5 Plications can be minimized or avoided has Most children with achondroplasia do well. How- The new information is incorporated into this report, ever, children affected with achondroplasia com- which is a revision of the original policy statement. monly have delayed motor milestones (Fig 3),12,13. Achondroplasia is the most common condition as- otitis media, and bowing of the lower Less sociated with severe disproportionate short commonly, infants and children may have serious The diagnosis can usually be made on the basis of health consequences related to hydrocephalus, clinical characteristics and very specific features on craniocervical junction compression, upper-airway obstruction, or thoracolumbar kyphosis. Although The guidance in this report does not indicate an exclusive course of treat- they are less common, anticipatory care should be ment or serve as a standard of medical care. Variations, taking into account directed at identifying children who are at high risk individual circumstances, may be appropriate.

6 And intervening to prevent serious sequelae. Most PEDIATRICS (ISSN 0031 4005). Copyright 2005 by the AMERICAN Acad- individuals with achondroplasia are of normal intel- emy of PEDIATRICS . ligence and are able to lead independent and pro- PEDIATRICS Vol. 116 No. 3 September 2005 771. Fig 1. Height for males with achondroplasia (mean standard deviation) compared with normal standard curves. The graph was derived from 189 males. (Reproduced with permission from J Pediatr. 1978;93:435-438.). ductive Because of their disproportionate must be tailored to a particular child's condition and short stature, however, a number of psychosocial needs. problems can arise. Families can benefit from antic- ipatory guidance and the opportunity to learn from THE PRENATAL VISIT. other families with children of disproportionate Pediatricians may be called on to counsel expect- short stature. ant parents whose fetus has achondroplasia or is The consensus-based guidance in this report is suspected to have achondroplasia because of recog- designed to help the pediatrician care for children nition on ultrasonography of disproportionate small with achondroplasia and their families.

7 Issues that stature. In some settings, the pediatrician will be the need to be addressed at various ages are discussed primary resource for counseling a family. At other (Table 1). These suggestions are not appropriate for times, counseling may already have been provided other chondrodysplasias, because each type has its to the family by a clinical geneticist and/or the ob- own natural history, complications, and specific stetrician. Because of a previous relationship with the guidelines. Irrespective of the availability of the family, however, the pediatrician may be called on to guidance in this report, it is important that pediatri- review this information and assist the family in the cians and parents also consult a physician with spe- decision-making process. cial experience and expertise concerning achondro- The diagnosis of achondroplasia in the fetus is plasia early in the child's life, because this report made most often with certainty when 1 or both par- only provides generally applicable suggestions that ents have this condition.

8 In this circumstance, the 772 HEALTH SUPERVISION FOR CHILDREN WITH ACHONDROPLASIA. Fig 2. Height for females with achondroplasia (mean standard deviation) compared with normal standard curves. The graph was derived from 214 females. (Reproduced with permission from J Pediatr. 1978;93:435-438.). parents are usually knowledgeable about the disor- trician should also discuss the natural history of der, the inheritance, and the prognosis for the off- achondroplasia, because it is the most likely expla- spring. More often, diagnosis of achondroplasia is nation for the findings. In cases in which the diag- first suspected late in gestation on the basis of long- nosis is unequivocally established either because of bone foreshortening incidentally discovered by ul- the familial nature of the disorder or by prenatal trasonography. With the frequent use of ultrasonog- molecular diagnosis (chorionic villus sampling at raphy, many cases of achondroplasia are first 11 13 weeks' gestation or amniocentesis after 15.)

9 Identified prenatally (after 26 weeks of gestational weeks' gestation), the pediatrician may consider the age). However, disproportionately short limbs are following steps as appropriate. observed in a heterogeneous group of conditions. Misdiagnosis and inaccurate prenatal counseling of 1. Review, confirm, and demonstrate laboratory or families is Confirmation of diagnosis imaging studies leading to the diagnosis. based on ultrasonographic features characteristic of 2. Explain the mechanisms for occurrence of achon- achondroplasia can be provided by molecular testing droplasia in the fetus and the recurrence risk for (FGFR3 mutational testing) of prenatal specimens. If the family. no such confirmation has yet been completed, cau- 3. Remember that at least 75% of cases of achondro- tion should be exercised when counseling the family. plasia occur in families in which both parents In this circumstance, the pediatrician should discuss have average stature.

10 In those cases, achondropla- the tentative nature of the diagnosis and alternatives sia in the offspring occurs because of a mutation that may explain the identified features. The pedia- in the gene. AMERICAN ACADEMY OF PEDIATRICS 773. Fig 3. Developmental screening tests in achondroplasia. The bar scale shows the percentage of achondroplastic children passing the item;. the black triangle on top of the bar shows the age at which 90% of normal children pass the same item. The graphs were derived from 197 affected individuals, obtained by questionnaire. (Reproduced with permission from Am J Med Genet. 1981;9:19-23.). 4. Review the natural history and manifestations of with ultrasonographic measurements at 14, 16, 18, achondroplasia, including 22, and 32 weeks of gestation to distinguish ho- 5. Discuss additional studies that should be per- mozygosity or heterozygosity from normal growth formed, particularly those to confirm the diagno- patterns in the fetus.