Outline

Growth: Pattern, Variability, and Timing

In studies of growth and development, the concept of pattern is an important one. In a general sense, pattern (as in the pattern from which articles of clothing of different sizes are cut) reflects proportionality, usually of a complex set of proportions rather than just a single proportional relationship. Pattern in growth also represents proportionality, but in a still more complex way, because it refers not just to a set of proportional relationships at a point in time, but to the change in these proportional relationships over time. In other words, the physical arrangement of the body at any one time is a pattern of spatially proportioned parts. But there is a higher level pattern, the pattern of growth, which refers to the changes in these spatial proportions over time.

Figure 2-1 illustrates the change in overall body proportions that occurs during normal growth and development. In fetal life, at about the third month of intrauterine development, the head takes up almost 50% of the total body length. At this stage, the cranium is large relative to the face and represents more than half the total head. In contrast, the limbs are still rudimentary and the trunk is underdeveloped. By the time of birth, the trunk and limbs have grown faster than the head and face, so that the proportion of the entire body devoted to the head has decreased to about 30%. The overall pattern of growth thereafter follows this course, with a progressive reduction of the relative size of the head to about 12% of the adult. At birth, the legs represent about one third of the total body length, while in the adult, they represent about half. As Figure 2-1 illustrates, there is more growth of the lower limbs than the upper limbs during postnatal life. All of these changes, which are a part of the normal growth pattern, reflect the “cephalocaudal gradient of growth.” This simply means that there is an axis of increased growth extending from the head toward the feet.

Another aspect of the normal growth pattern is that not all the tissue systems of the body grow at the same rate (Figure 2-2). Obviously, as the relative decrease of head size after birth shows, the muscular and skeletal elements grow faster than the brain and central nervous system. The overall pattern of growth is a reflection of the growth of the various tissues making up the whole organism. To put it differently, one reason for gradients of growth is that different tissue systems that grow at different rates are concentrated in various parts of the body.

Even within the head and face, the cephalocaudal growth gradient strongly affects proportions and leads to changes in proportion with growth (Figure 2-3). When the skull of a newborn infant is compared proportionally with that of an adult, it is easy to see that the infant has a relatively much larger cranium and a much smaller face. This change is an important aspect of the pattern of facial growth. Not only is there a cephalocaudal gradient of growth within the body, there also is one within the face. From that perspective, it is not surprising that the mandible, being farther away from the brain, tends to grow more and later than the maxilla, which is closer.

An important aspect of pattern is its predictability. Patterns repeat, whether in the organization of different-colored tiles in the design of a floor or in skeletal proportions changing over time. The proportional relationships within a pattern can be specified mathematically, and the only difference between a growth pattern and a geometric one is the addition of a time dimension. Thinking about pattern in this way allows one to be more precise in defining what constitutes a change in pattern. Change, clearly, would denote an alteration in the predictable pattern of mathematical relationships. A change in growth pattern would indicate some alteration in the expected changes in body proportions.

A second important concept in the study of growth and development is variability. Obviously, everyone is not alike in the way that they grow, as in everything else. It can be difficult but clinically very important to decide whether an individual is merely at the extreme of the normal variation or falls outside the normal range.

Rather than categorizing growth as normal or abnormal, it is more useful to think in terms of deviations from the usual pattern and to express variability quantitatively. One way to do this is to evaluate a given child relative to peers on a standard growth chart (Figure 2-4). Although charts of this type are commonly used for height and weight, the growth of any part of the body can be plotted in this way. The “normal variability,” as derived from large-scale studies of groups of children, is shown by the solid lines on the graphs. An individual who stood exactly at the midpoint of the normal distribution would fall along the 50% line of the graph. One who was larger than 90% of the population would plot above the 90% line; one who was smaller than 90% of the population would plot below the 10% line.

These charts can be used in two ways to determine whether growth is normal or abnormal. First, the location of an individual relative to the group can be established. A general guideline is that a child who falls outside the range of 97% of the population should receive special study before being accepted as just an extreme of the normal population. Second and perhaps more importantly, growth charts can be used to follow a child over time to evaluate whether there is an unexpected change in growth pattern. Pattern implies predictability. For the growth charts, this means that a child’s growth should plot along the same percentile line at all ages. If the percentile position of an individual relative to his or her peer group changes, especially if there is a marked change (see Figure 2-4, B), the clinician should suspect some growth abnormality and should investigate further. Inevitably, there is a gray area at the extremes of normal variations, at which it is difficult to determine if growth is normal.

A final major concept in physical growth and development is that of timing. Variability in growth arises in several ways: from normal variation, from influences outside the normal experience (e.g., serious illness), and from timing effects. Variation in timing arises because the same event happens for different individuals at different times—or, viewed differently, the biologic clocks of different individuals are set differently.

Variations in growth and development because of timing are particularly evident in human adolescence. Some children grow rapidly and mature early, completing their growth quickly and thereby appearing on the high side of developmental charts until their growth ceases and their contemporaries begin to catch up. Others grow and develop slowly and so appear to be behind, even though, given time, they will catch up with and even surpass children who once were larger. All children undergo a spurt of growth at adolescence, which can be seen more clearly by plotting change in height or weight (Figure 2-5), but the growth spurt occurs at different times in different individuals.

Growth effects because of timing variation can be seen particularly clearly in girls, in whom the onset of menstruation (menarche) gives an excellent indicator of the arrival of sexual maturity. Sexual maturation is accompanied by a spurt in growth. When the growth velocity curves for early-, average-, and late-maturing girls are compared in Figure 2-6, the marked differences in size between these girls during growth are apparent. At age 11, the early-maturing girl is already past the peak of her adolescent growth spurt, whereas the late-maturing girl has not even begun to grow rapidly. This sort of timing variation occurs in many aspects of both growth and development and can be an important contributor to variability.

Although age is usually measured chronologically as the amount of time since birth or conception, it is also possible to measure age biologically, in terms of progress toward various developmental markers or stages. Timing variability can be reduced by using developmental age rather than chronologic age as an expression of an individual’s growth status. For instance, if data for gain in height for girls are replotted, using menarche as a reference time point (Figure 2-7), it is apparent that girls who mature early, average, or late really follow a very similar growth pattern. This graph substitutes stage of sexual development for chronologic time to produce a biologic time scale and shows that the pattern is expressed at different times chronologically but not at different times physiologically. The effectiveness of biologic or developmental age in reducing timing variability makes this approach useful in evaluating a child’s growth status.

Methods for Studying Physical Growth

Before beginning the examination of growth data, it is important to have a reasonable idea of how the data were obtained. There are two basic approaches to studying physical growth. The first is based on techniques for measuring living animals (including humans), with the implication that the measurement itself does no harm and that the animal will be available for additional measurements at another time. The second approach uses experiments in which growth is manipulated in some way. This implies that the subject of the experiment will be available for study in some detail, and the detailed study may be destructive. For this reason, such experimental studies are largely restricted to nonhuman species.

The Nature of Skeletal Growth

At the cellular level, there are only three possibilities for growth. The first is an increase in the size of individual cells, which is referred to as hypertrophy. The second possibility is an increase in the number of the cells, which is called hyperplasia. The third is secretion of extracellular material, thus contributing to an increase in size independent of the number or size of the cells themselves.

In fact, all three of these processes occur in skeletal growth. Hyperplasia is a prominent feature of all forms of growth. Hypertrophy occurs in a number of special circumstances but is a less important mechanism than hyperplasia in most instances. Although tissues throughout the body secrete extracellular material, this phenomenon is particularly important in the growth of the skeletal system, where extracellular material later mineralizes.

The fact that the extracellular material of the skeleton becomes mineralized leads to an important distinction between growth of the soft or nonmineralized tissues of the body and the hard or calcified tissues. Hard tissues are bones, teeth, and sometimes cartilages. Soft tissues are everything else. In most instances, cartilage, particularly the cartilage significantly involved in growth, behaves like soft tissue and should be thought of in that group, rather than as hard tissue.

Growth of soft tissues occurs by a combination of hyperplasia and hypertrophy. These processes go on everywhere within the tissues, and the result is what is called interstitial growth, which simply means that it occurs at all points within the tissue. Although secretion of extracellular material can also accompany interstitial growth, hyperplasia primarily and hypertrophy secondarily are its characteristics. Interstitial growth is characteristic of nearly all soft tissues and of uncalcified cartilage within the skeletal system.

In contrast, when mineralization takes place so that hard tissue is formed, interstitial growth becomes impossible. Hyperplasia, hypertrophy, and secretion of extracellular material all are still possible, but in mineralized tissues, these processes can occur only on the surface, not within the mineralized mass. Direct addition of new bone to the surface of existing bone can and does occur through the activity of cells in the periosteum—the soft tissue membrane that covers bone. Formation of new cells occurs in the periosteum, and extracellular material secreted there is mineralized and becomes new bone. This process is called direct or surface apposition of bone. Interstitial growth is a prominent aspect of overall skeletal growth because a major portion of the skeletal system is originally modeled in cartilage. This includes the basal part of the skull, as well as the trunk and limbs.

Figure 2-19 shows the cartilaginous or chondrocranium at 8 and 12 weeks of intrauterine development. Cartilaginous skeletal development occurs most rapidly during the third month of intrauterine life. A continuous plate of cartilage extends from the nasal capsule posteriorly all the way to the foramen magnum at the base of the skull. It must be kept in mind that cartilage is a nearly avascular tissue whose internal cells are supplied by diffusion through the outer layers. This means, of course, that the cartilage must be thin. At early stages in development, the extremely small size of the embryo makes a chondroskeleton feasible, but with further growth, such an arrangement is no longer possible without an internal blood supply.

During the fourth month in utero, there is an ingrowth of blood vascular elements into various points of the chondrocranium (and the other parts of the early cartilaginous skeleton). These areas become centers of ossification, at which cartilage is transformed into bone in the process called endochondral ossification, and islands of bone appear in the sea of surrounding cartilage (see Figure 2-19, B). The cartilage continues to grow rapidly but is replaced by bone with equal rapidity. The result is that the amount of bone increases rapidly and the relative (but not the absolute) amount of cartilage decreases. Eventually, the old chondrocranium is represented only by small areas of cartilage interposed between large sections of bone, which assume the characteristic form of the ethmoid, sphenoid, and basioccipital bones. Growth at these cartilaginous connections between the skeletal bones is similar to growth in the limbs.

In the long bones of the extremities, areas of ossification appear in the center of the bones and at the ends, ultimately producing a central shaft called the diaphysis and a bony cap on each end called the epiphysis. Between the epiphysis and diaphysis is a remaining area of uncalcified cartilage called the epiphyseal plate (Figure 2-20, A). The epiphyseal plate cartilage of the long bones is a major center for their growth, and in fact, this cartilage is responsible for almost all growth in length of these bones. The periosteum on the surfaces of the bones also plays an important role in adding to thickness and in reshaping the external contours.

Near the outer end of each epiphyseal plate is a zone of actively dividing cartilage cells. Some of these, pushed toward the diaphysis by proliferative activity beneath, undergo hypertrophy, secrete an extracellular matrix, and eventually degenerate as the matrix begins to mineralize and then is rapidly replaced by bone. As long as the rate at which cartilage cells proliferate is equal to or greater than the rate at which they mature, growth will continue. Eventually, however, toward the end of the normal growth period, the rate of maturation exceeds the rate of proliferation, the last of the cartilage is replaced by bone, and the epiphyseal plate disappears. At that point, the growth of the bone is complete, except for surface changes in thickness, which can be produced by the periosteum.

Endochondral ossification also occurs at the mandibular condyle, which superficially looks like half an epiphyseal plate (Figure 2-20, B and C). As we will see, however, the cartilage of the condyle does not behave like an epiphyseal plate—and the difference is important in understanding mandibular growth.

Not all bones of the adult skeleton were represented in the embryonic cartilaginous model, and it is possible for bone to form by secretion of bone matrix directly within connective tissues, without any intermediate formation of cartilage. Bone formation of this type is called intramembranous ossification. This type of bone formation occurs in the cranial vault and both jaws (Figure 2-21).

Early in embryonic life, the mandible of higher animals develops in the same area as the cartilage of the first pharyngeal arch—Meckel’s cartilage. It would seem that the mandible should be a bony replacement for this cartilage in the same way that the sphenoid bone beneath the brain replaces the cartilage in that area. In fact, development of the mandible begins as a condensation of mesenchyme just lateral to Meckel’s cartilage and proceeds entirely by intramembranous bone formation (Figure 2-22). Meckel’s cartilage disintegrates and largely disappears as the bony mandible develops. Remnants of this cartilage are transformed into a portion of two of the small bones that form the conductive ossicles of the middle ear but not into a significant part of the mandible. Its perichondrium persists as the sphenomandibular ligament. The condylar cartilage develops initially as an independent secondary cartilage, which is separated by a considerable gap from the body of the mandible (Figure 2-23). Early in fetal life, it fuses with the developing mandibular ramus.

The maxilla forms initially from a center of mesenchymal condensation in the maxillary process. This area is located on the lateral surface of the nasal capsule, the most anterior part of the chondrocranium, but endochondral ossification does not contribute directly to formation of the maxillary bone. An accessory cartilage, the zygomatic or malar cartilage, which forms in the developing malar process, disappears and is totally replaced by bone well before birth, unlike the mandibular condylar cartilage, which persists.

Whatever the location for intramembranous bone formation, interstitial growth within the mineralized mass is impossible, and the bone must be formed entirely by apposition of new bone to free surfaces. Its shape can be changed through removal (resorption) of bone in one area and addition (apposition) of bone in another (see Figure 2-15). This balance of apposition and resorption, with new bone being formed in some areas while old bone is removed in others, is an essential component of the growth process. The formation of new bone from a cartilaginous predecessor or direct bone formation within mesenchyme often is referred to as modeling; changes in the shape of this new bone due to resorption and replacement are referred to as remodeling. Keeping this distinction in mind can make it easier to understand the following sections of this chapter.

Sites and Types of Growth in the Craniofacial Complex

To understand growth in any area of the body, it is necessary to understand (1) the sites or location of growth, (2) the type of growth occurring at that location, (3) the mechanism of growth (i.e., how growth changes occur), and (4) the determinant or controlling factors in that growth.

In the following discussion of sites and types of growth in the head and face, it is convenient to divide the craniofacial complex into four areas that grow rather differently: the cranial vault, the bones that cover the upper and outer surface of the brain; the cranial base, the bony floor under the brain, which also is the dividing line between the cranium and the face; the nasomaxillary complex, made up of the nose, maxilla, and associated small bones; and the mandible. The sites and types of growth are discussed in the following section of this chapter. The mechanism and determinants for growth in each area, as they are viewed from the perspective of current theories of growth control, are discussed in the following section.