In Great Britain some girls begin to menstruate in their 10th or 11th years, while others who are equally healthy may not experience menarche until they 'are 14, 15, or even older. Menarche is, however, only a single event in the combination of physical changes which constitute puberty. The adolescent growth spurt, the development of the breasts, and the growth of the pubic hair occur more or less concurrently, and take, on the average, about 3 years from beginning to completion, with menarche occurring usually in the latter half of this period (Tanner, 1962). At present we lack detailed information about the rate at which girls progress through the stages of puberty and about the relation of one event to another. Only longitudinal studies (i.e. studies in which the same individuals are examined repeatedly over a period of time) can provide this information, which would be helpful both to the clinician in distinguishing the normal from the abnormal, and to the neuro-endocrinologist in constructing hypotheses about the mechanisms by which puberty is controlled. Present knowledge is based on studies carried out on small numbers of children in the United States a generation ago, together with some German studies of a similar period (for literature see Tanner, 1962). The only recent European study in which the events of puberty have been followed longitudinally is the Harpenden Growth Study, which began 19 years ago in England and is still in progress. Anthropometric measurements have been taken, and the development of the breasts and pubic hair have been recorded photographically at 3monthly intervals throughout puberty. Though these data may be subject to certain biases, discussed below, they provide information available from no other source. This paper describes the extent of normal individual variation observed in the events of puberty among the girls of the Harpenden Growth Study. We discuss: (a) variation in the chrono-

https://adc.bmj.com/content/archdischild/44/235/291.full.pdf

Variations in pattern of pubertal changes in girls.

Mixed longitudinal data on the physical changes at puberty in 228 normal boys are presented together with normal standards for stages of genital and pubic hair development. The genitalia began to develop between the ages 9½ years and 13½ years in 95% of boys (mean = 11.6 ± 0.09) and reached maturity at ages varying between 13 and 17 (mean = 14.9 ± 1.10). The age at which pubic hair first appeared was not accurately determined, but its development through the later stages was studied. It reached the equivalent of an adult female distribution at a mean age of 15.2 ± 0.01 years. On average the genitalia reached the adult stage 3.0 years after they first began to develop; but some boys completed this development in as little as 1.8 years while others took as much as 4.7 years. Some boys complete the whole process in less time than others take to go from Stage G2 to Stage G3. The genitalia begin to develop before pubic hair is visible in photographs in practically all boys. The 41 boys in whom it could be studied reached their maximum rate of growth (peak height velocity) at a mean age of 14.1 ± 0.14 years. Very few boys (about 5%) reached peak height velocity before their genitalia were in Stage 4 and over 20% did not do so until their genitalia were adult. Peak height velocity is reached, on the average, nearly 2 years later in boys than in girls, but the boys9 genitalia begin to develop only about 6 months later than the girls9 breasts. Pubic hair appears about 1½ years later in boys than in girls.

https://adc.bmj.com/content/archdischild/45/239/13.full.pdf

Variations in the Pattern of Pubertal Changes in Boys

An epidemiological and genetical study of osteogenesis imperfecta (OI) in Victoria, Australia confirmed that there are at least four distinct syndromes at present called OI. The largest group of patients showed autosomal dominant inheritance of osteoporosis leading to fractures and distinctly blue sclerae. A large proportion of adults had presenile deafness or a family history of presenile conductive hearing loss. A second group, who comprised the majority of newborns with neonatal fractures, all died before or soon after birth. These had characteristic broad, crumpled femora and beaded ribs in skeletal x-rays. Autosomal recessive inheritance was likely for some, if not all, of these cases. A third group, two thirds of whom had fractures at birth, showed severe progressive deformity of limbs and spine. The density of scleral blueness appeared less than that seen in the first group of patients and approximated that seen in normal children and adults. Moreover, the blueness appeared to decrease with age. All patients in this group were sporadic cases. The mode of inheritance was not resolved by the study, but it is likely that the group is heterogeneous with both dominant and recessive genotypes responsible for the syndrome. The fourth group of patients showed dominant inheritance of osteoporosis leading to fractures, with variable deformity of long bones, but normal sclerae.

https://jmg.bmj.com/content/jmedgenet/16/2/101.full.pdf

Genetic heterogeneity in osteogenesis imperfecta.

There is currently widespread interest in the IGFs (IGF-I and IGF-II) and their roles in the regulation of growth and differentiation of an ever increasing number of tissues are being reported. This selective review focused on the current state of our knowledge about the structure of mammalian IGFs and the multiple forms of mRNAs which arise from alternative splicing and promoter sites which arise from gene transcription. Current progress in the immunological measurement of the IGF is reviewed including different strategies for avoiding binding protein interference. The results of measurements of serum IGF-I and IGF-II in fetus and mother and at various stages of postnatal life are described. Existing knowledge of the concentration of these peptides in body fluids and tissues are considered. Last, an attempt is made to indicate circumstances in which the IGFs are exerting their actions in an autocrine/paracrine mode and when endocrine actions predominate. In the latter context it was concluded that an important role for GH action on skeletal tissues via hepatic production of IGF-I and endocrine action of IGF-I on growth cartilage is likely.

Insulin-Like Growth Factors I and II. Peptide, Messenger Ribonucleic Acid and Gene Structures, Serum, and Tissue Concentrations

The current reference curves of stature and weight for the UK were first published in 1966 and have been used ever since despite increasing concern that they may not adequately describe the growth of present day British children. Using current data from seven sources new reference curves have been estimated from birth to 20 years for children in 1990. The great majority of the data are nationally representative. The analysis used Cole's LMS method and has produced efficient estimates of the conventional centiles and gives a good fit to the data. These curves differ from the currently used curves at key ages for both stature and weight. In view of the concerns expressed about the current curves and the differences between them and the new curves, it is proposed that the curves presented here should be adopted as the new UK reference curves.

https://adc.bmj.com/content/archdischild/73/1/17.full.pdf

Cross sectional stature and weight reference curves for the UK, 1990.

(C) Whole-year Velocity Standards: Chronological Age-based and Individual Type We now consider how to construct velocity standards, to answer our second question 'Has this child's rate of growth been within normal limits ?' We are again confronted with the alternatives of plotting against chronological or developmental age at adolescence and we have adopted the same solution as before. First we give, in the conventional manner, centiles plotted against chronological age, over the whole age span. These are calculated simply from two measurements a year apart, without using further longitudinal data. They depend on a two-occasion longitudinal study, nothing further. At adolescence these standards are greatly scattered by the phase-difference effect. If we know nothing about a boy except that he is 12 years old and grew 3 cm. during the last year, we must plot 3 cm. at 11 * 5 years and interpret this according to the chronological age centiles. If, however, we know that he is midpubescent, or that his skeletal age is 14 * 0 years, then in theory we could make a more effective interpretation if we had the appropriate standards. We have to remember, however, that in one important respect velocity standards differ from distance ones. In velocity standards a child does not have the same strong tendency to stay in the same centile position from one age to another; there is always a contrary tendency to a move from the outer centile positions towards a more central position in the subsequent year. Though a child can follow the 60th or even 70th centile of velocity from the pre-school years till maturity and end up a large but normal adult, a child who follows the 97th centile

https://adc.bmj.com/content/archdischild/41/219/454.full.pdf

R. H. Whitehouse

Papers

Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. II