Prader-Willi or Angelman syndrome in familial 15q11----q13 deletion of maternal origin?
Explore the source record for details and available documents.
Chromosome Deletion↗
Biomedical subjects
A Prader
Publications and source records attributed to A Prader.
Progressive high frequency hearing loss: an additional feature in the syndrome of congenital adrenal hypoplasia and gonadotrophin deficiency.
In an earlier report, we found that X-linked congenital adrenal hypoplasia may be associated with gonadotrophin deficiency. This combination has since been confirmed by many others. At the last examination, our patients were 22.4, 19.9 and 17.5 years old. They were doing well on replacement therapy with hydrocortisone, fluorohydrocortisone, and long-acting testosterone, but in all of them, a progressive hearing loss had appeared, starting at high frequencies at about 14 years of age. The loss progressed with age to lower frequencies, and the oldest patient had some remaining hearing capacity at 125-500 Hz only with a perceptive hearing loss of -95 dB at frequencies above 500 Hz. It is concluded that patients with this syndrome should be examined for hearing loss. X-linked adrenal hypoplasia may also be associated with glycerol kinase deficiency and myopathy. A molecular XP-deletion has suggested a locus for hypogonadotrophic hypogonadism distal to the glycerol kinase and adrenal hypoplasia loci. The observations in our patients suggest that the locus for at least this type of X-linked deafness may be in the same area.
Adolescent↗
Testicular adrenal-like tissue (TALT) in congenital adrenal hyperplasia: detection by ultrasonography.
In a consecutive series of 15 male adolescents and young adults with congenital adrenal hyperplasia (CAH), the size, shape, firmness and echostructure of the testes were assessed. The latter was abnormal in 7 patients under long standing treatment with glucocorticoids (group I). In 8, 5 under and 3 off treatment for several years, ultrasonography (US) was normal (group II). On the basis of the US findings the patients were placed in two groups. In group I, the testes had a heterogeneous ultrasonographic pattern; clinically, most felt hard and irregular, although their volume was normal. Sperm count in 3 patients was 5.0 to 14.4 x 10(6)/ml. Five patients have 21-hydroxylase deficiency that was diagnosed in early infancy and had salt-wasting; two have 11-beta-hydroxylase deficiency that was diagnosed late and had no salt-wasting. In group II, testicular volume, shape, firmness and echostructure were normal. All have 21-hydroxylase deficiency, no history of salt-wasting and were diagnosed late. Sperm counts in 3 patients off treatment were 10.5 to 66.0 x 10(6)/ml. In severe cases with a history of salt loss, TALT with deficient spermiogenesis seems likely despite treatment. In mild cases, TALT is absent and spermiogenesis may be normal even without treatment. US is much more accurate in assessing the testes than palpation.
Adolescent↗
Molecular, cytogenetic, and clinical investigations of Prader-Willi syndrome patients.
Thirty-seven patients presenting features of the Prader-Willi syndrome (PWS) have been examined using cytogenetic and molecular techniques. Clinical evaluation showed that 29 of these patients fulfilled diagnostic criteria for PWS. A deletion of the 15q11.2-q12 region could be identified molecularly in 21 of these cases, including several cases where the cytogenetics results were inconclusive. One clinically typical patient is deleted at only two of five loci normally included in a PWS deletion. A patient carrying a de novo 13;X translocation was not deleted for the molecular markers tested but was clinically considered to be "atypical" PWS. In addition, five cases of maternal heterodisomy and two of isodisomy for 15q11-q13 were observed. All of the eight patients who did not fulfill clinical diagnosis of PWS showed normal maternal and paternal inheritance of chromosome 15 markers; however, one of these carried a ring-15 chromosome. A comparison of clinical features between deletion patients and disomy patients shows no significant differences between the two groups. The parental ages at birth of disomic patients were significantly higher than those for deletion patients. As all typical PWS cases showed either a deletion or disomy of 15q11.2-q12, molecular examination should provide a reliable diagnostic tool. As the disomy patients do not show either any additional or more severe features than typical deletion patients do, it is likely that there is only one imprinted region on chromosome 15 (within 15q11.2-q12).
Adolescent↗
A physiological mode of puberty induction in hypogonadal girls by low dose transdermal 17 beta-oestradiol.
Transdermal 17 beta-oestradiol administration (17 beta-E2), used mainly in menopausal women, allows a continuous 17 beta-E2 delivery through the skin into the systemic circulation, avoiding intestinal and hepatic passage. In order to explore whether transdermal 17 beta-E2 could be used for the induction of puberty, 17 beta-E2 patches with low dose delivery were administered in nine prepubertal girls with Turner syndrome (bone age greater than 10.5 years) for a mean period of 2.2 years. Treatment schedule: 5 micrograms/day for 6-9 months, 10 micrograms/day for 6-9 months, 25 micrograms/day for long-term substitution; addition of cyclic gestagen p.o. after 18-24 months. Breast development started within 3 months of therapy and menstruation occurred after 2 years. Growth rate increased from 3.2 to 5.0 cm/year during the 1st year of therapy, height prediction did not change. Serum oestradiol (E2) and urinary E2 conjugates increased proportionally with 17 beta-E2 doses, serum oestrone (E1) rose much less. The possibility to imitate time course, clinical events and hormonal changes of normal puberty, the absence of adverse drug reactions and the excellent acceptance and easy mode of application suggest that transdermal 17 beta-E2 is optimally suited for hormonal substitution in girls with hypogonadism.
Administration, Cutaneous↗
Pubertal growth in chronic renal failure.
We evaluated the growth records of 15 boys and 14 girls who developed end-stage renal failure before or during puberty and who were regularly followed from the onset to the end of their pubertal growth spurt. Height data were smoothed by using the kernel estimation method. Mean values for age, height, and height velocity at defined points of the pubertal growth period were compared with those of normal children entering puberty both at an average and late age. The start of the pubertal growth spurt was delayed by 2.5 y in both sexes. Its duration and intensity were significantly reduced. Mean pubertal height gain was 17.3 cm in boys and 13.9 cm in girls, i.e. 58 and 48% of that observed in the late maturing control group. Mean height at the onset of the pubertal spurt in the patients was the same as that in the late maturing healthy girls and 1.0 SD below that of corresponding boys. During the pubertal growth spurt, mean height declined to -2.9 SD in boys and -2.3 SD in girls. Although skeletal maturation was increasingly retarded, we did not observe accelerated growth velocity during late puberty. Our data indicate that most patients reaching end-stage renal failure before or during puberty irreversibly lose growth potential during this period. Renal transplantation did not consistently improve pubertal growth.
Adolescent↗
MRI in Cockayne syndrome type I.
MRI findings are reported from two patients with Cockayne syndrome (CS) type I, aged 11 and 37 years. Changes were compatible with diffuse white matter hypomyelination. Basal ganglia calcification was present in both, marked cerebellar atrophy in the older patient. MRI may support the diagnosis of CS in the appropriate clinical context. The view that CS is a dysmyelinating disorder is further substantiated.
Adult↗
The testicular lesion and sexual differentiation in congenital lipoid adrenal hyperplasia.
Congenital lipoid adrenal hyperplasia results in deficient virilization of genetic male infants, indicating that gonadal testosterone biosynthesis is impaired in such patients. In order to better define the characteristics of the gonadal lesion, we studied a Japanese genetic male infant with congenital lipoid adrenal hyperplasia who underwent bilateral orchiectomy at 14 months of age. The basal serum testosterone was low before and after orchiectomy (6.6 +/- 1.1 vs. 9.5 +/- 1.3 ng/dl), though it was higher at 9 days of age (30 ng/dl). A stimulation test with human chorionic gonadotropin at 12 months of age yielded no testosterone response (7----less than 5 ng/dl). At the time of the surgical intervention, the external genitalia were completely female but Wolffian duct derivatives (epididymides and vasa deferentia) were well developed. The microscopic examination of the testes revealed an increased number of Leydig cells which were filled with abundant lipoid material.- The above data demonstrate that the fetus produced a sufficient amount of testicular testosterone for a male Wolffian duct development. This indicates a quantitative difference in androgen requirements for the male sexual development of the external genitalia and the Wolffian ducts.
Adrenal Hyperplasia, Congenital↗
Physical growth of Swiss children from birth to 20 years of age. First Zurich longitudinal study of growth and development.
Physical growth from birth to adulthood in healthy Swiss children born 1954-1956 is described. The data are based on the First Zurich Longitudinal Study in which 137 individuals of each sex have been followed from birth to adulthood between 1954 and 1976. Distance standards of 20 anthropometric measurements such as weight, height and head circumference are presented as mean values and standard deviations or as median values (for weight and skinfold thickness) with smoothed empirical centiles. Velocity standards are provided for seven anthropometric parameters. The following standard growth charts for clinical use are presented: weight, length/height and head circumference in the perinatal period, in the age range of 0-48 months and in the age range of 1-18 years (including some data on puberty), as well as weight for length/height and height velocity (cross-sectional and peak height centered). Comparison of the growth standards with those of previous Swiss studies and of recent foreign studies revealed only minor differences. Various aspects relevant for the clinical use of growth standards, such as measurement error or secular trend, are discussed.
Adolescent↗
Craniometaphyseal dysplasia with increased bone turnover and secondary hyperparathyroidism: therapeutic effect of calcitonin.
Explore the source record for details and available documents.
Bone Diseases, Developmental↗
[Indications for the surgical intervention in endocrine disorders of the ovaries].
Endocrine disturbances of the ovaries with indication for surgery are rare. They require close cooperation between paediatric endocrinologist and paediatric surgeon. Clarification is mainly based on endocrinological findings and ultrasound examination of the ovaries. The following disturbances are discussed: Central (genuine and peripheral or pseudo-) precocious puberty, hormonally active ovarian tumours and cysts, the various forms of dysgenesis of the gonads, especially tumour-prone mixed gonadal dysgenesis with XO/XV karyotype, the syndromes of polycystic ovaries, and girls who grew up as boys with male external genitals.
Adolescent↗
Effects of the long-acting somatostatin analogue SMS 201-995 in an infant with intractable diarrhea.
The long-acting somatostatin analogue SMS 201-995 was administered to a six-month-old infant with intractable diarrhea after failure of conventional treatment. During eight weeks of treatment, the secretory component of the diarrhea was positively influenced with a reduction of daily stool weight and stool sodium concentration. Plasma levels of growth hormone were markedly, and levels of insulin, IGF I, gastrin, pancreatic polypeptide, VIP, and neurotensin moderately decreased. Linear growth was also inhibited. The patient unexpectedly died from fulminant colitis at a time, when the dosage had been reduced from 18 to 3.5 micrograms/kg/day. The relationship, if any, between therapy with SMS 201-995 and the colitis remained unclear. It is concluded that SMS 201-995 can be effective in reducing secretory diarrhea in infants. However, further studies are necessary to assess the safety of its administration in this age group.
Antidiarrheals↗
The ulnar-mammary syndrome: an autosomal dominant pleiotropic gene.
A family is described in which four male patients spanning three generations present a consistent clinical entity, the major features of which include: ulnar finger and fibular toe ray defects; delayed growth and onset of puberty, obesity, hypogenitalism and diminished sexual activity; hypoplasia of nipples and apocrine glands with subsequently diminished ability to perspire. Additional findings in single cases include pyloric, anal and subglottic stenosis. To date, another 12 patients in three families have been described with this syndrome. The condition appears to be inherited as an autosomal dominant trait with full penetrance and highly variable expression.
Abnormalities, Multiple↗
Growth hormone response to a standardised exercise test in relation to puberty and stature.
Growth hormone (GH) was measured before and 10 minutes after a standardised bicycle exercise test (duration 15 minutes) in 37 short children (group 1: mean (SD) age 12.8 (3.5) years; mean (SD) bone age 10.4 (3.6) years; mean (SD) height standard deviation score (SDS) -2.8 (0.7], 16 tall children (group 2: mean age 12.9 (2.8) years; mean bone age 13.9 (1.4) years; mean height SDS 3.0 (0.8], and 30 normal children (group 3: mean age 13.3 (3.2) years; mean bone age 12.8 (3.4) years; mean height SDS -0.4 (0.8]. Results of GH are expressed as mean (SEM). The pre-exercise GH was similar in the three groups (group 1, 8.0 (2.3) mU/l, group 2, 8.5 (2.5) mU/l, and group 3, 8.3 (2.3) mU/l). There was a significant rise in GH after exercise in all three groups. GH after exercise was higher in group 2 (35.1 (2.5) mU/l) compared with groups 1 and 3 (17.8 (3.0) and (20.8 (3.2) mU/l). Post-exercise GH was less than 10 mU/l in 29 children (34% total; 49% group 1, 6% group 2, and 34% group 3). There was a positive relation between post-exercise GH and both bone age and public hair stage. Multiple regression analysis revealed that relevant predictors of a rise in GH with exercise were different for the sexes in these children with varying stature: for boys, bone age and pubic hair stage; for girls, height and height SDS. All the tall girls were in puberty. No statistical relation was observed between post-experience GH and cardiovascular response to exercise, time of day of exercise, time of eating before exercise, and plasma insulin or insulin to glucose ratio at time of exercise. We conclude that the GH response to the physiological stimulus of exercise is higher in puberty compared with childhood. Therefore, although children may be suspected of having GH deficiency after a failure of GH to increase after exercise, a non-response may be a normal finding in prepubertal children, independent of stature.
Adolescent↗
Transient ovarian testosterone and androstenedione hypersecretion: a cause of virilization or premature pubarche in prepubertal girls.
In 2 girls with signs of androgen overproduction, the usual causes were excluded. Patient 1 (3.6 years) presented with hypertrophy of the clitoris, patient 2 (7.8 years) with pubic and axillary hair. Urinary steroids and plasma dehydroepiandrosterone, 17-hydroxyprogesterone and estradiol were normal, but testosterone and androstenedione elevated in both cases. Echography showed polycystic ovaries. Testosterone and androstenedione returned to normal after laparotomy and removal of ovarian cysts in patient 1, and spontaneously in patient 2, in whom puberty started later appropriately for bone age.
Androstenedione↗
Lack of bromocriptine-induced reduction of predicted height in tall adolescents.
Fifteen girls and five boys with excessive predicted adult height (chronological age, 10.1-14.6 yr; bone age, 11.0-14.0 yr) were treated with bromocriptine (two doses; 2.5 mg/day) to reduce their final height. After a mean treatment period of 1.14 yr (range, 0.6-1.75 yr) we did not find a reduction of predicted adult height [difference, -0.5 +/- 3.5 (+/- SD) cm according to Bayley and Pinneau's tables (P = NS) and +0.2 +/- 2.5 (+/- SD) cm according to the method of Tanner (P = NS)]. Mean peak plasma GH concentrations after TRH administration before and during bromocriptine were 51.5 +/- 49.4 and 58.5 +/- 50.7 mU/L, respectively. The wide range of the GH values may be explained by physiological variation in this age group. After ingestion of 2.5 mg bromocriptine a significant increase in plasma GH occurred within 3 h in six adolescents tested. Our results do not support the concept that bromocriptine may reduce predicted adult height in tall adolescents by decreased GH secretion or acceleration of skeletal maturation.
Adolescent↗
Comparison of two tests to recognize or exclude 5 alpha-reductase deficiency in prepubertal children.
Plasma testosterone (T, nmol/l) and dihydrotestosterone (DTH, nmol/l) were measured in 54 children and young adults with male pseudohermaphroditism (46XY, no defect of steroid biosynthesis) 4 h after im injection of testosterone propionate (25 mg/m2, group 1, N = 18), or before and 2, 4 and 6 days after hCG (5000 IU/m2 im, group 2, N = 36). The response to hCG was also studied in 5 control children (unilateral cryptorchidism, group 3) and that to testosterone propionate in a gonadectomized child with confirmed 5 alpha-reductase deficiency. Mean T (133.1 +/- 14.0, SEM) and DHT (17.1 +/- 2.6) in group 1 were higher than in group 2 (17.3 +/- 2.1 and 2.9 +/- 0.4), but there was not significant difference in the T/DHT ratios (group 1: 10.7 +/- 2.0; group 2: 7.2 +/- 0.6). Following testosterone-propionate, there was a negative correlation of T with age (r = -0.723). After hCG, T and DHT were lower in the prepubertal children than in those under 2 or over 10 years, and the T/DHT-ratio rose with age. Two children from group 1 had a T/DHT-ratio above 18, but urinary aetiocholanolone/androsterone (Ae/A) ratios were normal. In the child with 5 alpha-reductase deficiency, the T/DHT ratio was 60, and the urinary Ae/A ratio high. We concluded that the two tests are suitable for confirming or excluding 5 alpha-reductase deficiency in prepubertal children, in whom basal DHT is too low for evaluation, but that physiological age-related changes in 5 alpha-reductase activity have to be taken into consideration.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗