Lassi Alvesalo

Sex chromosomes and human growth

Abstract Studies on tooth crown size and structure of individuals with various sex chromosome anomalies and their normal male and female relatives have demonstrated differential direct effects on growth of genes on the human X and Y chromosomes. The Y chromosome promotes growth of both tooth enamel and dentin, whereas the effect of the X chromosome on tooth growth seems to be restricted to enamel formation. Enamel growth is decisively influenced by cell secretory function and dentin growth by cell proliferation. It is suggested that these differential effects of the X and Y chromosomes on growth explain the expression of sexual dimorphism in various somatic features, such as the size, shape and number of teeth, and, under the assumption of genetic pleiotropy, torus mandibularis, statural growth, and sex ratio. Future questions concern, among other topics, the Y chromosome and the mineralization process, concentric control of enamel and dentin growth, and gene expression.

Permanent tooth sizes in 46, XX‐males

Measurements of permanent tooth sizes in four XX-males showed their teeth to be smaller than those of male controls and similar in size to those of female controls. The teeth of the XX-males were smaller than those of their first-degree male relatives and of the same size as those of three of their mothers. The teeth of three fathers of XX-males were similar in size to control males and the teeth of three mothers of XX-males were similar in size to control females. The detailed knowledge that exists regarding the sequence and timing of tooth crown development allows the following implications to be made from our results. Growth retardation in XX-males is of primary genetic origin and is due to the absence of the gene(s) normally located on the Y-chromosome. Growth retardation, compared to normal males, is apparent and final three years after birth, conceivably begins after 2--3 months of foetal life and persists during childhood. It is unlikely that XX-males have had a Y-chromosome at any stage. If maleness is caused by a recessively inherited translocation or a mutational acquisition of the testis-determining gene(s), the genes influencing growth are not involved in either mechanism.

The phenotype of 45,X females: an anthropometric quantification

Twenty-five anthropometric measurements were recorded from 48 adult 45,X females, 24 of their first-degree female relatives, and 95 control females. When 45,X females were compared with their female relatives and control females they were smaller in most dimensions, the largest differences being found in weight, stature, sitting height, arm length, leg length, bi-iliac diameter, bitrochanteric breadth and wrist width. No significant differences were found in head dimensions. The comparison after allowance for size showed that 45,X females are relatively smaller in stature, sitting height, arm length, leg length and bitrochanteric breadth and larger in bideltoid breadth, waist breadth, upper arm circumference, chest circumference and triceps skinfold. However, in proportion to height the relative lengths of sitting height, arm length and leg length were similar to those of normal females. The mother-45,X daughter correlation coefficients were significantly larger than those of sister-45,X sister pairs in body dimensions whereas they were more similar in head dimensions. The present findings suggest the presence of genes on the X chromosome having effect on growth in general. This conclusion is in accordance with the results of several earlier studies which have indicated an X-chromosomal influence on stature, tooth size and enamel thickness.

Sizes of Deciduous Teeth in 45,X Females

Deciduous teeth of eleven Finnish 45,X females were examined, and their tooth sizes were found to be smaller than those of control females. This finding might be explained by the decreased amount of the products of the growth-promoting factors located in the X and Y chromosomes.

Tooth crown size in human females with 45,X/46,XX chromosomes

Permanent tooth sizes in 15 Finnish females with a 45,X/46,XX chromosome constitution were measured and compared with those of normal females, first-degree female relatives and 45,X females. Mesiodistal crown diameters of the 45,X/46,XX mosaic females were smaller than those of normal females but similar to those of females with pure 45,X chromosome constitution. Labiolingual crown diameters of the 45,X/46,XX mosaics were near normal, being consistently larger than those of 45,X females. The mesiodistal crown sizes are consistent with a decrease in enamel thickness in 45,X/46,XX mosaic females. The difference in labiolingual dimension between teeth of 45,X/46,XX mosaic females and 45,X females may relate to a gradual normalization of growth when normal 46,XX cells are mixed with defective 45,X cells.

Maternal smoking and tooth formation in the foetus. II. Tooth crown size in the permanent dentition

Altogether 2159 pregnancies among black and white Americans in the Collaborative Perinatal Study and dental casts from their children at the age of 6-12 years were studied to determine the effect of maternal smoking on permanent tooth crown dimensions. A trend of reduction, similar to that observed in the deciduous second molars, was found in the permanent first molars and also in the mesio-distal dimension of permanent incisors in relation to sex and race of the children and smoking habits of the mother. In terms of peak in their mitotic growth, the results can be interpreted to indicate a sensitive period of intra uterine development from the 24th to 28th gestational weeks. Comparisons of postnatal body size and differential correlation patterns in affected tooth dimensions with early postnatal body and head size between smokers and non-smokers, suggests that maternal smoking during pregnancy may have an effect on basic growth of the head and body and/or the developmental process that impacts tooth development at some specific sensitive period also during the postnatal formation of these tooth crowns.

Dental morphology of 45,XO human females: Molar cusp area, volume, shape and linear measurements

A three-dimensional analysis of the maxillary first molars of five 45,XO females and comparison with normal females and males demonstrated a reduction of cusp areas and volumes in the 45,XO females. Mesiodistal and faciolingual dimensions were also reduced. The reductions in basal area and volume were greater in the later developing, distal cusps. In normal females the second X chromosome apparently does not exert an effect on the cusp height but increases the basal area. The results further indicate that the Y chromosome in normal males increases both cusp height and basal area. The steepest cusps were found in 45,XO females while the shallowest were in the control males. Both sex chromosomes thus seem to affect the shape of the cusp but the resulting phenotypes differ.

Taurodontism in 47,XXY Males: An Effect of the Extra X Chromosome on Root Development

Effects of an extra X chromosome on root development were studied in males with a 47, XXY chromosome constitution. Occurrence of taurodontism in the permanent molars of the lower jaw was noted from orthopantomograms of 30 Finnish 47,XXY males, 16 of their first-degree relatives, and a sample of 157 normal males and females. Nine, or 30%, or the 47, XXY males had at least one mandibular molar which was classified as taurodont. Only hypotaurodont teeth were found, and the teeth affected were all either second or third molars. None of the control relatives showed taurodontism. In the population sample, four individuals, or 2.5%, had taurodont teeth. A change in the mitotic activity of the cells of the developing teeth is one possible factor that can affect root formation leading to the development of taurodontism.

Maternal and Gestational Influences on Deciduous and Permanent Tooth Size

Although there have been suggestions that prenatal factors could affect crown dimensions (Bailit and Sung, Archs Oral Biol 13:155-166, 1968; Cohen, Baum, Garn, Osario and Nagy, in: Orofacial Growth and Development, Dahlberg and Graber, eds., Mouton Publishers, The Hague, 1977, pp 119-126), limitations of sample size and investigative design restrict conclusions on the magnitude of the influences. However, using newly-acquired odontometric data on selected participants in the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke (NCPP), it is now possible to show systematic effects of three maternal and six developmental conditions on mesiodistal and buccolingual dimensions of both deciduous and permanent teeth. The basic sample consists of 870 white participants studied at the time of their seven-eightyear psychological examinations in 1972 and 1973. They were selected from six cooperating institutions from the Atlantic seaboard and the West Coast (Niswander and Gordon, The Women and Their Pregnancies, D.H.E.W., Washington, 1972). Diabetes, hypothyroidism, and hypertension were the three maternal conditions selected for exploration. Gestation length, birth weight, and birth length were among the fetal or developmental variables studied. The odontometric analyses primarily involved the permanent incisors, first molars and deciduous cheek teeth (dc through dm2). A group of clinically normal children was also included for comparison, since single-source odontometric standards for deciduous and permanent teeth did not exist at the time the project was conceived. Mean crown dimensions of the normal NCPP group proved to be virtually indistin-

Size of the Alveolar Arch of the Mandible in Relation to that of the Maxilla in 45,X Females

Length and width of the alveolar arch of the mandible and maxilla were determined from hard stone casts of 45,X females (Turner syndrome), female first-degree relatives, and population control females. Adjusted mean values (covariance adjusted for age, previous orthodontic treatment, and number of lost permanent teeth) for mandibular arch width were larger in 45,Xfemales than in normal controls, both absolutely and, more clearly, in relation to the maxillary arch. The total absolute length of the mandibular arch was slightly reduced in 45,X females. The broader and shorter alveolar arch of the mandible in relation to the narrower but normal-length maxillary arch reflects imbalanced facial growth in subjects with one X-chromosome instead of the normal two.