High prevalence of primary ovarian insufficiency in girls and young women with Nijmegen breakage syndrome: evidence from a longitudinal study.

CONTEXT: Nijmegen breakage syndrome (NBS) is a severe chromosomal instability disorder characterized by microcephaly, growth retardation, immune deficiency, and predisposition for malignancy. It is caused by hypomorphic mutations in the NBN gene, which product belongs to the protein complex critical for processing DNA double-strand breaks during mitotic and meiotic recombination. Data on gonadal function in patients with NBS are limited. OBJECTIVE: Growth and sexual development, along with hormonal assays, were evaluated in girls and young women with NBS homozygous for c.657_661del5 mutation. STUDY DESIGN AND PATIENTS: The group comprised 37 girls and young women with NBS (ages, 0.17-24.25 yr), followed between 1993 and 2008. Patients were divided into three age groups: 1) 1-3 yr; 2) 4-9 yr; and 3) 10 yr and older. Growth, puberty, concentrations of gonadotropins and 17-beta-estradiol, bone age, and pelvic ultrasound were assessed. RESULTS: None of the patients presented a typical growth spurt; the adult height ranged between the 3rd and 25th centiles. Median bone age was delayed by 4.05 yr. Pubarche reached stadium P2 in eight patients and P3 in two patients. In all but one girl, thelarche did not exceed Th2, with low 17beta-estradiol levels. Gonadotropin levels showed a biphasic pattern, with median FSH values of 55.0, 10.9, and 81.9 IU/liter, and LH of 3.2, 0.8, and 21.0 IU/liter in consecutive age groups. Ultrasound visualized small ovaries or solid streaks and the hypoplastic uterus. CONCLUSIONS: Primary ovarian insufficiency and the associated hypergonadotropic hypogonadism are hallmark manifestations in girls and young women with NBS. Our findings emphasize the need for long-term endocrinological and interdisciplinary supervision of these patients.

Weight deficit at birth and Turner's syndrome.

Turner's syndrome (TS) is one of the most frequent diseases accompanied by growth deficiency. Though developmental disorders have been observed in the fetal period, there has been disagreement as to whether short stature is frequent in newborn girls with Turner's syndrome. Hence we attempted to determine the incidence of 'small for gestational age' in TS compared with healthy newborns girls delivered at term above -2 SD (body length and weight) for gestational age. The medical records of 548 girls with TS recruited from Polish university and district hospitals were screened, with 468 of them delivered at term (gestational age > or =38 weeks) being included in this study. Mean weight (+/- SD) at birth was 2963 +/- 444 g, which was below the normal value for gestational age in nearly 90%. The mean birth weight deficiency was 600 g, but exceeded 1000 g in over 10%. When a newborn girl delivered at term has a marked weight deficit, Turner's syndrome should be considered. This is especially so when the girl is a product of a first pregnancy, when routine karyotyping is recommended. The condition may arise from a partial dysfunction of a gene or genes on the X-chromosome involved in the control of fetal growth.

[Turner's syndrome: subjects with a normal body mass at birth grow taller than born small for gestational age]. / Zespól Turnera: lepszy wzrost uzyskuja chore urodzone z prawidlowa masa ciala.

BACKGROUND: Body mass deficit at birth is one of the characteristic features observed in Turner's syndrome (TS). Body mass is lower than expected for gestational age in about 90% of TS-babies, and is below -2 SD (i.e. "small for gestational age") in about 20% of patients. OBJECTIVES: The aim of the study was to compare the growth courses of TS-girls born with normal and deficient body mass. PATIENTS: A group of 157 TS-girls, delivered at term (> or =38 weeks of gestation), were studied. Body mass of 80 girls ranged from -0.5 to +0.5 SD and body length was above -2 SD (AGA group); another 54 girls had body mass below -2 SD and body length above -2 SD (disproportional SGA group), and 23 girls had both body mass and length below -2 SD (proportional SGA group). METHODS: Turner's syndrome was confirmed by chromosome analysis. Body mass at birth (BMB) was related to the norms for gestational age (GA) designed by Usher and McLean. Newborns, whose BMB was lower than -2 SD for GA, were considered small for gestational age (SGA). Postnatal body height and mass values were related to Polish norms for females with Turner's syndrome and to the norms for healthy female population. RESULTS: In the spontaneously growing TS-girls from the AGA group, a total of 275 measurements of body mass and height were carried out, the respective numbers for DSGA and PSGA groups were 176 and 100. Mean differences between the actual and expected body height for the AGA, DSGA and PSGA groups amounted to 0.40+/- 1.02, -0.21+/-0.88 and -0.95+/-0.80 SD TS, respectively, all means differing highly significantly (p<0.001) from each other. CONCLUSION: It may be concluded that spontaneously growing girls with Turner's syndrome, who had a normal (for gestational age) body mass at birth, attain a higher stature than girls with body mass deficit.