Who is achondroplasia found in

Your doctor can diagnose your child by looking at his or her features. This can help confirm a diagnosis. Blood tests may also be ordered to look for the defective FGFR3 gene. If any complications arise, then your doctor will address those issues. For instance, antibiotics are given for ear infections and surgery may be performed in severe cases of spinal stenosis. There may also be an increased risk of heart disease later in life. If you have achondroplasia, you may need to make some physical adaptations, such as avoiding impact sports that could damage the spine.

However, you can still live a full life. Study looked at longevity link between mothers and daughters. Certain exercises to strengthen your hamstring, glutes, and core can help improve lordosis posture and ease pain.

Try these five! Caudal regression syndrome, or sacral agenesis, is a rare condition where the lower spine doesn't fully form before birth. Here's what you should know. Mermaid syndrome is a severe and often fatal congenital abnormality involving fused limbs, which have been described as resembling a mermaid's tail.

According to an observational study in , couples, there was a 35 percent increase in the chance of birth defects in newborns if the father…. Krabbe disease is a rare and life threatening disorder of the nervous system.

Sturge-Weber syndrome is a rare neurological disorder present at birth. Learn about its symptoms, causes, diagnosis, and treatment. Alkaptonuria is a rare genetic disorder that causes homogentisic acid to build up in your body. Learn about the symptoms, causes, and treatment. The FGFR3 gene makes a protein called fibroblast growth factor receptor 3 that is involved in converting cartilage to bone.

FGFR3 is the only gene known to be associated with achondroplasia. Most people who have achondroplasia have average-size parents. In this situation, the FGFR3 gene mutation occurs in one parent's egg or sperm cell before conception. Other people with achondroplasia inherit the condition from a parent who has achondroplasia.

People who have achondroplasia have abnormal bone growth that causes the following clinical symptoms: short stature with disproportionately short arms and legs, short fingers, a large head macrocephaly and specific facial features with a prominent forehead frontal bossing and mid-face hypoplasia.

Infants born with achondroplasia typically have weak muscle tone hypotonia. Because of the hypotonia, there may be delays in walking and other motor skills. People with achondroplasia commonly have breathing problems in which breathing stops or slows down for short periods apnea.

Other health issues include obesity and recurrent ear infections. Adults with achondroplasia may develop a pronounced and permanent sway of the lower back lordosis and bowed legs. The problems with the lower back can cause back pain leading to difficulty with walking. Achondroplasia is diagnosed by characteristic clinical and X-ray findings in most affected individuals. In individuals who may be too young to make a diagnosis with certainty or in individuals who do not have the typical symptoms, genetic testing can be used to identify a mutation in the FGFR3 gene.

Some result in a very poor prognosis e. Others may actually result in an ameliorating effect [ 35 ]. The possible outcomes are sufficiently complex that formal counseling should be recommended in all such instances. A number of such coincidental co-occurrences have been described in individuals with achondroplasia. Of particular note is the occurrence of achondroplasia plus Down syndrome. It should be expected that this arises on occasion: Down syndrome is more frequent in the offspring of older mothers, while achondroplasia is more common in children of older fathers; and, of course, maternal and paternal ages tend to co-vary.

Seven instances have been reported in the literature [ 36 , 37 ] but there are certainly many more that have not been reported including three personal observations. Unfortunately, these two disorders have features that, together, can result in very severe problems — hypotonia in both; craniocervical junction issues in both; restrictive pulmonary disease in both. Not surprisingly, then, this combination often results in death in infancy [ 36 ].

Thousands of years after its recognition, nearly a century after its clinical description, and a quarter century after it clear clinical and radiologic delineation, the molecular basis of achondroplasia was discovered. Shiang et al. Rapidly it was demonstrated that nearly all instances of achondroplasia are caused by FGFR3 mutations [ 39 , 40 ]. This locus homogeneity was not particularly surprising.

What was unexpected is that virtually all mutations in FGFR3 arise in the same nucleotide pair and result in the same glycine to arginine substitution GR in the FGFR3 protein [ 40 ]. This specific mutation is at least or fold more frequent than expected [ 41 , 42 ].

FGFR3 is one of four fibroblast growth factor receptors in humans. All are cell surface receptors that influence cellular proliferation. FGFR3 is comprised of an extracellular domain with three immunoglobulin-like regions, a transmembrane domain and an intracellular tyrosine kinase [ 43 ] Fig. It can be pictured as an empty cup sitting on the surface of cells. It is particularly prevalent on the surface of chondrocytes that give rise to cartilaginous bone [ 44 ], but is also expressed in calvarial sutures [ 45 ], testes [ 46 ], and the brain [ 47 ].

This results in dimerization of the receptors, transphosphorylation and trans-activation of tyrosine kinases, and propagation of an intracellular signal [ 43 ]. Although downstream signaling is complex [ 48 , 49 ], overall the signal within the growth plate of cartilaginous bones is negative.

That is, overall FGFR3 is a negative regulator of chondrocytic bone growth through shortening of the proliferative phase and accelerating terminal differentiation [ 49 ]. The mutation that results in achondroplasia is a gain of function mutation [ 50 ] rather than an inactivating mutation. It most likely results in ligand independent activation of FGFR3 [ 50 , 51 ]. This, then, is constitutive activation of an inhibitory signal.

Dysplasias can be sorted into families in which members differ mostly by severity [ 52 ]. Other disorders within the achondroplasia family and discussed below are also caused by different mutations in FGFR3. Severity seems to be a consequence of a graded series of relative activation of FGFR3 [ 53 , 54 , 55 ]. Virtually all of the clinical features and medical problems of achondroplasia arise because of the consequent abnormalities of cartilaginous bone growth — either directly, or because of disproportionate growth of cartilaginous bone compared with nearby structures derived from other tissues.

Why is the mutation resulting in the GR amino acid substitution so frequent? This is related to the paternal age effect which has already been briefly mentioned. It has been recognized for a long time that certain genetic disorders arising through new mutations occur far more frequently in the offspring of older fathers [ 56 ]. That phenomenon is particularly marked in achondroplasia [ 17 ]. Both the origin of this paternal age effect and the exceedingly high apparent mutation rate have a single basis [ 41 , 42 ].

That basis also helps explain why all mutations in sporadic cases of achondroplasia are paternal in origin [ 57 ]. It seems that certain mutant protein products, including of FGFR3 , are positively selected for in sperm precursor cells spermatogonial stem cells. Once such a mutation occurs there will be clonal expansion of cells containing the mutation and consequent enrichment within the spermatogonial population.

This positive selection within germinal precursors, rather than an actual increased mutation rate, probably explains the prevalence of achondroplasia. If, as seems to be the case, such selection only occurs in male germinal precursors, this also explains the paternal origin of virtually all instances of achondroplasia.

Furthermore, since clonal expansion will cause more and more enrichment with time [ 58 ], fertilization involving a sperm with such a mutation becomes more likely with advancing paternal age. Achondroplasia is one of a small number of so-called RAMP disorders — recurrent, autosomal dominant, male biased, paternal age effect disorders — all of which likely arise because of their positive selective effect on spermatogonia.

Other disorders for which there is convincing evidence of similar effects include Apert syndrome, Noonan syndrome, and multiple endocrine neoplasia type 2B [ 59 ]. The vast majority of individuals with achondroplasia are diagnosed in early infancy, although prenatal recognition has become more frequent and more accurate. It is critical that diagnosis not be delayed since certain complications can only be prevented through assessment in early infancy see Special Concerns in the Young Infant.

No formal clinical diagnostic criteria have been published, but well defined clinical and radiologic characteristics of achondroplasia [ 12 ] usually allow for virtual certainty.

In certain circumstances, particularly in the markedly premature neonate [ 60 ], clinical diagnosis may be especially challenging. Clinical features Figs. Clinical features include:. Small stature. Small size is not a constant feature in infants, who may have lengths within the normal range [ 61 ]. Short limbs and rhizomelic disproportion. Rhizomelic proximal shortening is uniformly present at least in the arms [ 12 , 62 ] , although variable in severity.

Often there are redundant skin folds of the upper arms and the thighs. Head size is usually large at birth and remains so throughout life [ 61 ]. Variable frontal and parietal bossing prominence and bumpy protuberance is usually present Fig.

Midfacial retrusion. Underdevelopment of cartilaginous bones of the face result in flattening of the entire midface and a flat nasal bridge, a short nasal spine and anteversion of the nose Fig.

Small chest. In addition to the chest being often smaller than average [ 63 ], the ribs are overly compliant. This results in paradoxical movement with inspiration, which is often misinterpreted as being retractions reflecting respiratory distress. Thoracolumbar kyphosis. Virtually all infants develop a dynamic thoracolumbar kyphosis in infancy [ 64 ], but this is not present at birth. Limited elbow extension. Unlike most other joints, the elbows are stiff and may, with age, become progressively stiffer.

Short fingers and trident configuration of the hands Fig. Bowing of the mesial segment of the legs. Bowing is not congenital. It most often arises in early childhood and may progress at unpredictable rate and extent until growth is completed.

Most infants with achondroplasia are hypotonic [ 65 ]. The body phenotype is shown in individuals of different ages: Left to right — infancy, early childhood, childhood and adulthood. In all, note the rhizomelic shortening of the limbs, which are disproportionately short compared with the trunk.

In the infant and young child macrocephaly is evident. Six portraits of children with achondroplasia. The variability of craniofacial features is evident. Lower left and lower center photographs originally published in Pauli RM Osteochondrodysplasias with mild clinical manifestations: A guide for endocrinologists and others.

Growth Genet Horm —5. Anteroposterior radiograph of the pelvis and femora in an infant with achondroplasia. Characteristic findings include a squared-off pelvis, horizontal acetabula, very narrow sacrosciatic notch, characteristic proximal femoral radiolucency, and short and robust femora. Arm radiograph in a newborn with achondroplasia. Although there are generalized metaphyseal abnormalities and shortening of all of the long bones, characteristics here are not as diagnostically helpful as those shown in Fig.

Hands in achondroplasia, well illustrating brachydactyly and here, asymmetric trident configuration — excess separation between the third and fourth fingers. Originally published in Pauli RM Achondroplasia. In summary, those features that are diagnostically most helpful in the neonate and young infant include: rhizomelic shortening of the arms; macrocephaly; midfacial hypoplasia and nasal anteversion; small chest; short fingers and trident configuration; hypermobility of the hips and knees; hypotonia.

Not all infants will display all of these features. Diagnostic confirmation requires radiographic assessment. Although achondroplasia is a metaphyseal dysplasia, generalized metaphyseal changes are mild and nonspecific.

Typically a complete skeletal survey or a hemi-survey of one side of the body will be obtained Figs. However, most of the diagnostically critical features will be appreciated on a single anteroposterior radiograph of the pelvis and femora Fig.

Only rarely should diagnostic uncertainty remain after careful clinical and radiologic assessment. When needed, molecular testing is straightforward. Because nearly all instances of achondroplasia arise from a change in the same base pair of FGFR3 [ 40 ], targeted mutation analysis is the routinely employed molecular test. Testing is available commercially from a large number of laboratories. Only very rarely and in very unusual circumstances will any additional molecular testing be warranted.

On rare occasions, when molecular confirmation has been sought, a common mutation will not be found. In such an event, further analysis of FGFR3 is warranted [ 66 ], since occasional instances of other FGFR3 pathogenic variants have been documented previously [ 67 , 68 , 69 , 70 , 71 ]. Note, however, that in some of these there is inadequate clinical documentation [ 67 , 69 ], while in others such as the case described by Takagi et al. In the most general sense, any short limb dwarfing disorder would fall within the spectrum of the differential diagnosis of achondroplasia.

Only a few conditions are likely to result in any substantial confusion, however. Distinct mutations in FGFR3 may cause a number of allied conditions with shared features and differing mostly in severity [ 52 ]. The most important of these is hypochondroplasia Fig. On the other hand, that the natural history of these two disorders is in certain ways in fact quite different makes issues of differentiating between them in any particular patient sometimes difficult but often critically important [ 82 ].

For example, temporal lobe dysgenesis, seizures and cognitive abnormalities are far more common in those with hypochondroplasia [ 82 , 83 , 84 ], while issues related to the craniocervical junction are far less frequent in hypochondroplasia than in achondroplasia.

Clinically, marked craniofacial disproportion is much less common in hypochondroplasia than in achondroplasia, and the severity of rhizomelia and brachydactyly generally less than that seen in achondroplasia. Radiologically, all features seen in those with hypochondroplasia are also present in those with achondroplasia. However, three radiologic features uniformly present in achondroplasia but virtually never evident in hypochondroplasia help with this distinction: the characteristic proximal femoral radiolucency of achondroplasia is rarely evident in those with hypochondroplasia; rhizomelic disproportion of the arms, uniform in achondroplasia, is usually absent in hypochondroplasia when ratios of long bone lengths are assessed [ 85 ]; the moderate to marked abnormalities of facial bone contour of achondroplasia are not present in those with hypochondroplasia.

General body habitus present in hypochondroplasia. Cursory examination could easily miss the presence of a bone growth disorder in such a child. Originally published in Pauli RM Osteochondrodysplasias with mild clinical manifestations: A guide for endocrinologists and others.

Nonetheless, occasionally molecular testing is warranted in distinguishing hypochondroplasia and achondroplasia. If a child being assessed clearly has either achondroplasia or hypochondroplasia but it is uncertain which of these is present, the most parsimonious approach is to test for the achondroplasia pathogenic variant first.

If it is present, the diagnosis is confirmed. If absent and since virtually all individuals with achondroplasia have the so-called common mutation and the child clearly has one or the other of these diagnoses, then a diagnosis of hypochondroplasia can be made. With such a result, hypochondroplasia may have arisen either because of a mutation in FGFR3 or at some other locus, but making that distinction is not nearly so important as making the distinction between achondroplasia and hypochondroplasia.

Thanatophoric dysplasia [ 86 , 87 ] was originally described by Maroteaux et al. It is probably about as com6mon as is achondroplasia [ 15 , 89 ]. The clinical and radiographic characteristics are uniformly similar to, but much more severe than the same characteristics in achondroplasia Figs.

There are two forms of thanatophoric dysplasia. Both are caused by distinct mutations in FGFR3. Rarely should there be diagnostic confusion between thanatophoric dysplasia and achondroplasia. Clinical phenotype of thanatophoric dysplasia, type I. All features are far more severe than those seen in babies with achondroplasia Fig. Anteroposterior radiograph of the pelvis and femora in thanatophoric dysplasia, type I.

Here, too, qualitatively most of the abnormal characteristics are similar to those seen in achondroplasia, but quantitatively all of them are much more severe. Note the so-called telephone receiver femora. Homozygous achondroplasia Fig. Of course, it only arises if both parents have heterozygous achondroplasia. Theoretically, it should arise rarely secondary to a new mutation when only on parent has achondroplasia, or secondary to two mutational events when neither parent has achondroplasia, but those probabilities are remote; in fact, neither event has to date been reported.

Like thanatophoric dysplasia, this should rarely cause diagnostic confusion. On the left is an infant with typical, heterozygous achondroplasia. On the right is his older sister who had homozygous achondroplasia. Note the far greater limb foreshortening and much smaller stature in the latter. Prior to the age at which developmental disability can be recognized and before acanthosis nigricans develops, confidently differentiating achondroplasia and SADDAN syndrome requires molecular evaluation.

Such assessment should be pursued, particularly in instances in which global developmental delays more severe than those typically seen in achondroplasia are identified. A number of other rare dysplasias secondary to FGFR3 mutations have been described e.

None is likely to be encountered. In addition to the FGFR3 family of bone dysplasias, other mutations in this same gene can cause Crouzon syndrome with acanthosis nigricans [ 97 ], Muenke syndrome [ 98 ], isolated acanthosis nigricans with or without slow linear growth [ 99 , , ], and slow linear growth without unequivocal features of a bone dysplasia being present [ 81 ].

Loss of function mutations in contrast to the gain of function that results in achondroplasia cause an overgrowth disorder in both sheep [ ] and humans [ ]. Achondroplasia is a metaphyseal dysplasia. Generally, however, other metaphyseal dysplasias, such as the Schmid type of metaphyseal dysplasia [ ] and cartilage-hair hypoplasia [ ] are straightforwardly distinguished by clinical features, radiographic features and age of presentation.

Any rhizomelic dwarfing process might occasionally cause diagnostic confusion. Pseudoachondroplasia [ ] deserves mention. Despite its name, it is primarily a spondyloepiphyseal dysplasia sharing little except rhizomelic dwarfism with achondroplasia. It has none of the craniofacial features that are present in achondroplasia. It is typically not diagnosed until the 2nd or 3rd year of life.

Radiographs are utterly dissimilar. Most of those with achondroplasia will have a normal or near normal life expectancy. However, there is an increased risk for premature death [ , , ] related not only to sudden unexpected deaths in infancy see below but also, it appears, to cardiovascular complications in mid-adult life [ ]. However, in addition, that multicenter mortality study shows that there has been a dramatic decrease in deaths, including sudden unexpected deaths, in young children with achondroplasia, most likely secondary to recognition of their special risks and aggressive evaluation and intervention related to the craniocervical junction [ ].

Most of the medical issues that need to be addressed in individuals with achondroplasia are presented by organ system, below. However, there are two concerns — craniocervical junction constriction and restrictive pulmonary disease — that may be of major concern very early in infancy. These are summarized here. The first of these is a particularly important reason along with parental needs that diagnosis be confirmed as quickly as possible in infancy, so that critical evaluations can be completed in a timely manner.

The single event that precipitated three-plus decades of investigation is as follows [ ]. A baby boy was born to a mother of average stature and a father who had achondroplasia. He had been neurologically normal and had no antecedent illness. Postmortem assessment found no cause of death and a diagnosis of sudden infant death syndrome SIDS was made. A new sister, also with achondroplasia, was born a year later. Not because of any suspicion that SIDS and achondroplasia were linked, but rather because of the then favored notion that there was strong familiality on a genetic basis for SIDS [ ], polysomnography was completed.

This led to consideration of the possibility that it was their shared diagnosis of achondroplasia that placed them at risk. A retrospective inquiry of 20 centers in which substantial numbers of individuals with achondroplasia had been evaluated yielded 10 additional patients with achondroplasia who had died unexpectedly [ ].

Of those, four had evidence for severe damage to the medulla and upper cervical cord Fig. Subsequent reassessment of the craniocervical junction in the original proband showed that histologically he, too, had evidence of hypoxic damage Fig.

Gross pathologic features from the craniocervical junction of the spinal cord in an infant with achondroplasia who died suddenly and unexpectedly. There is gross indentation of the cord as well as cystic lesions secondary to hypoxic damage.

Originally published in Pauli RM et al. J Pediatr — [ ]. Histologic findings from the cervicomedullary junction in the infant described in the text.

Left shows severe pyknosis secondary to hypoxic damage, compared with, right , a normal control of comparable age. It was already known that infants with achondroplasia have decreased growth of the basicranium, which is of cartilaginous origin, and a small foramen magnum [ , ]. The diminution of foraminal size arises directly from the decreased growth of cartilaginous bone as well as, perhaps, from abnormality of the synchondroses [ ].

This probably effectively diminishes even further the space actually available. Although direct compression of the spinal cord can occur see below , it is more likely that the apneic deaths arise from compression of vertebral arteries at or near the craniocervical junction.

The events surrounding the deaths included ones in which uncontrolled head movement could have resulted in craniocervical compression. Therefore, we postulated that those deaths arose from either acute or chronic compression of vasculature at the craniocervical junction resulting in hypoxic damage to the central respiratory control centers in the medulla.

In turn, such hypoxic damage can result in diminished central respiratory control, and, in the most severe instances, irreversible apnea. Computerized tomography in five infants with achondroplasia, demonstrating the variability of conformation of the foramen magnum. Subsequent experience has clearly demonstrated that without careful assessment some infants with achondroplasia will die because of craniocervical junction issues [ 8 , ].

A number of studies have provided important additional information. For example, Reid et al. They also showed that the non-lethal respiratory problems were alleviated by suboccipital decompressive surgery [ ].

Although the interpretation by Tasker et al. Further, Tasker et al. Although the risk of death remains uncertain, consensus has developed that it is substantial. Hecht and her colleagues [ , ] have estimated that the risk for death in the first year of life may be as high as 7. Although there was early disagreement about whether this is a real phenomenon [ ], subsequently a consensus arose D. Rimoin, personal communication, at least to the fact that this is a real concern.

Between and we prospectively evaluated 53 infants with achondroplasia who were referred without explicit neurologic or respiratory concerns [ 8 ]. Uniform, comprehensive assessments demonstrated that 5 of the 53 had problems of sufficient severity to justify suboccipital decompressive surgery. In every such instance, marked abnormality of the upper cervical cord was demonstrated intraoperatively.

Therefore, anatomic, neurologic and respiratory characteristics, together, allow identification of those babies who likely are at highest risk to experience life-threatening events related to the craniocervical junction. Initially this was most often by computerized tomography [ ] Fig.

This approach continues to offer certain advantages. First, it allows measurement of the size of the foramen for which standards are available [ ] and which was a demonstrable predictor of need for decompression [ 8 ]. Secondly, most often it can be completed without sedation or anesthesia. This may be a serious consideration given concerns about the effects on synaptogenesis of anesthesia in young babies [ ]. This should be performed in a sleep center comfortable with assessing infants.

Interpretation can be complicated by restrictive pulmonary issues with decreased respiratory reserve. Emphasis, of course, should be on assessing central apnea and hypopnea. In our center, only in infants who have worrisome features based on these initial assessments is magnetic resonance imaging MRI completed.

Generally, we now obtain the MRI in both flexion and extension [ , ]. MRI, too, requires careful interpretation specific to achondroplasia. All infants will have narrowing at the foramen magnum.

Most infants with achondroplasia will have obliteration of the posterior subarachnoid fluid layer Fig. These features must be interpreted in light of clinical characteristics, since clearly some babies with all of these features do well and thrive without decompressive surgery personal observations.

Prudence commends that MRI studies be reviewed by a neuroradiologist with experience and expertise in achondroplasia in order to limit unneeded surgeries. The presence of either a T-2 signal abnormality Fig. Sagittal views of magnetic resonance imaging of the cervical cord in four infants with achondroplasia.

Various alternatives have been suggested and used. Such prospective investigations of what evaluation scheme is most helpful are desperately needed but very difficult to develop.

Better visualization of neural tissue is forthcoming, but usually sedation or general anesthesia will be needed because of the length of the procedure. Often multiposition MRI is elected [ , ]. Flow studies may be of some help as well in determining whether surgical intervention is warranted [ , ]. Three dimensional CT might be another alternative [ ], as might be diffusion tensor MRI imaging [ ].

This obviates the need for anesthesia and the possible risks that this entails both immediate and, at least speculatively, long term [ ]. However, while sufficient for many purposes, detail obtained by fast-MRI is not sufficient to definitively determine the need for surgery related to the craniocervical junction.

It has even been suggested that no imaging at all be routinely done in infants with achondroplasia [ ]. However, this recommendation appears to be based on no objective, published evidence [ ].

Table 1 summarizes the advantages and disadvantages of various approaches to imaging in infancy. There is clear need to objectively assess which approach or approaches are most advantageous.

At a minimum, standards for MRI or fast-MRI features and measurements in infants with achondroplasia need to be generated [ ], if this is to become the routine method of anatomic evaluation. Some have also suggested a step-wise protocol. Bober, personal communication While logical, such stepwise assessment has not yet been rigorously assessed and should not be embraced without evidence to support it.

Likewise, the suggestion that polysomnography is not predictive of craniocervical junction concern, and so implying that it is not an essential assessment [ ], is based on a small, retrospective series of patients, of whom many were well outside the age range of relevance, and is not worthy of further consideration. Somatosensory evoked potentials could be of considerable benefit in identifying infants at high risk.

Early experience, however, suggested that most infants with achondroplasia showed abnormalities of somatosensory evoked potentials, and that it failed to discriminate between those at high risk and others [ 8 ]. However, other investigations suggest that there may be a role of evoked potentials in the assessment of the craniocervical junction in infants with achondroplasia [ , , ].

Should any prospective studies of efficacy of evaluations be initiated in the future, somatosensory evoked potential testing should probably be included in such a protocol. Counseling regarding cautions that should be exercised with every infant with achondroplasia are based, in part, on the presumed mechanism of injury at the craniocervical junction and, in part, on the circumstances that have been observed in instances of unexpected infant deaths.

As noted, risk likely is related to a combination of foramen magnum constriction, the typically large head of achondroplasia and poor head control, which often takes longer to develop in infants with achondroplasia. Uncontrolled head movement should, then, be avoided. There is anecdotal evidence that deaths are particularly likely to arise in babies who have been placed in vertical automatic swings [ 4 , ]; in fact, I am aware of at least six instances in which babies with achondroplasia have died in vertical automatic swings.

There also have been multiple instances of life-taking or life-threatening events in car seats [ ] and personal observations. Use of a neck roll in strollers, and, particularly, in car seats. When restrained, infants with achondroplasia, who have large and prominent occiputs, will have their necks in a forced flexed position. In those infants where assessment demonstrates unequivocal cord compression resulting in clinical abnormalities, then suboccipital decompression should be completed urgently [ , ].

Operative intervention may be particularly challenging because of the unique anatomy of the skull in achondroplasia [ , ]. Major complications of decompressive surgery are rare [ ] and the quality of life of those undergoing decompression is not compromised long term [ ].

If, as suggested, such intervention is lifesaving, then with universal assessment and intervention 4—5 lives per year should be spared in the United States, and around per year worldwide. As noted, there is evidence that routine assessment and intervention as outlined does decrease mortality in infants with achondropasia [ ].

Infants with achondroplasia often have small chests [ 63 ]. In addition, there is increased compliance of the rib cage, sometimes dramatically so. That excess compliance is manifest as paradoxical movement with inspiration in most young infants with achondroplasia — sinking inward principally of the inferolateral part of the chest, but also often substernally.

Mild deformity of the chest may also be present [ ], including lateral indentations and pectus excavatum. The combination of these features — small chest, presumably but not certainly reflecting smaller anatomic lung volumes, inefficient chest mechanics, and chest deformity — together may result in smaller effective lung volumes.

Despite these features, most babies suffer no evident consequences. Predictably it does result in more rapid desaturations with physiologic sloppiness of central respiratory control or with minor obstructive events, making interpretation of polysomnography more challenging in young infants. In a small proportion this set of features can result in chronic hypoxemia. This is particularly likely in those living at high altitude personal observations. Chronic hypoxemia can be of sufficient severity to result in failure to thrive presumably because of increased work of breathing , rarely respiratory failure, and, potentially, cor pulmonale if not addressed [ , , ].

Assessment is straightforward. Clinically persistent marked tachypnea, secondary feeding difficulties because of that tachypnea, additional signs of chronic respiratory distress and failure to thrive may be present.

In all babies with achondroplasia polysomnography needs to be completed for other indications see above. This also will provide a long oximetry sample. Saturation dips into the high 80s are normal in infants with achondroplasia personal observation. In addition, daytime spot oximetries, both during active alert time and, particularly, during feedings for example, may be helpful. Chest circumference measures compared with achondroplasia standards may also be of some help [ 63 ].

In those with restrictive pulmonary disease, the help of a pediatric pulmonologist should be sought. Oxygen supplementation alone may be sufficient to maintain saturations and reverse failure to thrive. If not, tracheostomy may be needed. In all, it has been temporary. Given that the activating mutation of FGFR3 that results in achondroplasia causes a general inhibition of endochondral bone growth, of course one would anticipate that all of the long bones of the body will grow slowly; and they do.

Small stature is the signal characteristic of achondroplasia. Although length at birth may be normal [ 61 , ], slow growth is evident shortly thereafter. Moderate to marked short stature is present in all affected individuals. Remarkably few parents of average children understand the importance of routine measurement of growth — that growth is an excellent, nonspecific indication of general well-being.

Therefore, standard growth charts specific for achondroplasia [ 61 , ] should be used Fig. In addition to these hand-smoothed curves, statistically more rigorous growth curves for a U. Diagnostic specific linear growth charts for females left and males right with achondroplasia. Comparable curves for average statured individuals are shaded. Clinton, SC: Jacobs [ ]. These standards are based on a U. Growth references for other populations are also available [ , , ].

The achondroplasia mutation modifies rather than negates other genetic determinants of growth [ ]. Height variability in individuals with achondroplasia seems to correlate just as strongly with parental heights as it is in average individuals.