Decanalization of weight and stature during childhood and adolescence

The probabilities that children and adolescents alter their positions to non-adjacent canals (decanalization) on the current NCHS growth charts have been estimated. In this context, canals are the zones between the major percentile levels (5th, 10th, 25th, 50th, 75th, 90th, and 95th) that are shown on the charts. These probabilities were calculated for one- and 2-year intervals, beginning at each annual age from 3–16 years, using serial data for weight and stature from 329 male and 303 female participants in the Fels Longitudinal Study. The probabilities of particular types of decanalizations, categorized by the initial canal and the direction of the change in relative level (decrease/loss; increase/gain) are presented. The probabilities for 1-year intervals were very low and, therefore, they are not presented. Additionally, probabilities were calculated for transitions from the canal between the 5th and 10th percentiles to the zone below the 5th percentile and from the canal between the 90th and 95th percentiles to the zone above the 95th percentile. Both these transitions are shifts to levels that are outside the normal range, and are more common than decanalization. The probabilities of decanalization and of transitions from the normal range were generally larger for weight than for stature except for transitions from the canal between the 90th and 95th percentiles to the zone beyond the 95th percentile. The probabilities for both weight and stature tended to be larger for changes toward the medians than for changes from the medians. Decanalizations that involved increases in level were significantly related to advanced skeletal maturation at ages younger than the usual age of peak height velocity and to retarded skeletal maturation at ages older than the usual age of peak height velocity. Am. J. Hum. Biol. 10:351–359, 1998. © 1998 Wiley-Liss, Inc.     

Management of children with short stature

325 patients referred to an endocrine clinic with short stature were reviewed, 32 (9.8%) were above the third centile for height and maintained normal growth velocities, fourteen (4.3%) have not had assessment completed. Of 279 children in whom the cause of short stature was established, 140 (50%) had constitutional short stature/delayed puberty (CSS/DP). Seventy-three (26%) had idiopathic growth hormone deficiency (GHD), complete in 23, while 66 patients (34%) had short stature due to other causes. Girls presented earlier (mean age 11.9) than boys (mean age 13.3) and GHD patients earlier than CSS/DP patients with bimodal peaks at 12 and 16 years. Male CSS/DP patients reached their mid pubertal point later than normal at 16.06 +/- 1.19 years (p less than .05) while in GHD males the mid pubertal age was 16.6 years (p less than .05). In female patients with short stature no significant pubertal delay was observed. The average growth velocity of complete GHD patients pre treatment was 3.7 cms/year. Velocity rose to 6.2 cms/year on human growth hormone (HGH) extract and rose further to 8.1 cms/year on biosynthetic HGH. In partial GHD patients the average pre-treatment velocity of 4.3 cm/year rose to an average of 6.0 cm/yr on HGH extract and maintained this velocity on biosynthetic HGH.     

Concern about tall stature during adolescence and depression in later life

OBJECTIVE: This retrospective cohort study aimed to examine the long-term psychosocial outcomes for women assessed or treated during adolescence for tall stature. METHOD: Women assessed or treated for tall stature identified from the records of Australian paediatricians were eligible to participate. Psychosocial outcomes were measured using the depression, mania and eating disorders modules of the Composite International Diagnostic Interview (CIDI), the SF-36, and an index of social support. RESULTS: There was no significant difference between treated and untreated women in the prevalence of 12 month or lifetime major depression, eating disorders, scores on the SF-36 mental health summary scale, or the index of social support. However, compared with the findings of population-based studies, the prevalence of major depression in both treated and untreated tall girls was high (12 month prevalence: untreated 10.7%, treated 11.2%; lifetime prevalence: untreated 29.4%, treated 26.6%). Factors significantly associated with lifetime major depression in this study were self-reported difficulties during adolescence being the reason for seeking a medical assessment of height (OR 2.25, 95% CI 1.4-3.6) and a negative experience of the assessment or treatment procedures (OR 2.04, 95% CI 1.4-3.0). CONCLUSION: Long-term follow-up of a large cohort of tall girls showed that psychological outcomes among both treated and untreated women were poor and that the intended psychosocial benefit of treatment may not have been realized. The findings highlight the importance of attending to the mental health of adolescents presenting for management of conditions where self-concept and body image are a primary focus.     

Dominant inheritance of microcephaly with short stature

A family is reported in which microcephaly has been observed in at least three generations. The pedigree is most consistent with autosomal dominant inheritance. In addition to microcephaly, affected individuals exhibit significantly short stature, ocular anomalies and simple, protruding ears. Intellectual function is in the normal or borderline range.     

Autosomal dominant partial lipodystrophy associated with Rieger anomaly, short stature, and insulinopenic diabetes

We describe the clinical findings and natural history of an autosomal dominant form of partial lipodystrophy found in four affected individuals from three generations in the same family. The lipodystrophy was present from infancy/early childhood, involved primarily the face and local areas on the buttocks, and was nonprogressive. Affected individuals also had the Rieger anomaly, midface hypoplasia, short stature, retarded bone age, and hypotrichosis. An affected woman developed insulinopenic diabetes mellitus at 39 yr and another had glucose intolerance at 55 yr.     

Copy number variants in patients with short stature

Height is a highly heritable and classic polygenic trait. Recent genome-wide association studies (GWAS) have revealed that at least 180 genetic variants influence adult height. However, these variants explain only about 10% of the phenotypic variation in height. Genetic analysis of short individuals can lead to the discovery of novel rare gene defects with a large effect on growth. In an effort to identify novel genes associated with short stature, genome-wide analysis for copy number variants (CNVs), using single-nucleotide polymorphism arrays, in 162 patients (149 families) with short stature was performed. Segregation analysis was performed if possible, and genes in CNVs were compared with information from GWAS, gene expression in rodents'' growth plates and published information. CNVs were detected in 40 families. In six families, a known cause of short stature was found (SHOX deletion or duplication, IGF1R deletion), in two combined with a de novo potentially pathogenic CNV. Thirty-three families had one or more potentially pathogenic CNVs (n=40). In 24 of these families, segregation analysis could be performed, identifying three de novo CNVs and nine CNVs segregating with short stature. Four were located near loci associated with height in GWAS (ADAMTS17, TULP4, PRKG2/BMP3 and PAPPA). Besides six CNVs known to be causative for short stature, 40 CNVs with possible pathogenicity were identified. Segregation studies and bioinformatics analysis suggested various potential candidate genes.     

Progressive laryngotracheal stenosis with short stature and arthropathy

Laryngotracheal stenosis is rare in adults, especially in the absence of a malignancy. It is most commonly caused by fibrosis following endotracheal intubation or tracheal trauma. Other conditions causing progressive airway narrowing include the mucopolysaccharidoses and autoimmune disorders. With the exception of storage diseases, there are no well-defined genetic disorders with progressive airway narrowing as a common complication. We have evaluated three unrelated individuals with this potentially life-threatening finding, all of whom have a previously unrecognized condition. Each patient had short stature and joint stiffness with no evidence for infectious, inflammatory, or metabolic diseases as a cause of their condition. None of our patients had clinical findings indicative of known skeletal dysplasias or storage diseases. They had minor facial anomalies which included deeply set eyes, bushy eyebrows, and flat midface. Given the unique findings of our patients including adult onset critical tracheal stenosis, short stature, progressive joint limitation, and distinct facial anomalies, we conclude that they have a previously undescribed condition. Am. J. Med. Genet. 80:241–246, 1998. © 1998 Wiley-Liss, Inc.     

Unusual type of brachydactyly associated with short stature and facial anomalies. A new syndrome?

We report on a 10-year-old boy with short stature, mild microcephaly, malar hypoplasia, highly arched palate, prominent upper incisors, micrognathia, and unusual digital anomalies involving the proximal phalanges of fingers 2-5 of both hands. To our knowledge, this is a hitherto undescribed syndrome.     

Karyotype/phenotype correlation in females with short stature

We studied 60 females who presented with short stature. The main aim was to determine the effect of karyotype variation on phenotype. A somatic feature score was calculated for each case depending on the presence of 17 clinical somatic changes known to occur in Turner syndrome. Karyotype studies showed the following results: 45,X (n = 22): 46,XX (n = 11); 45,X/46,XX (n = 10); 46,XX/46,Xi(Xq) (n = 4); 46,XX/46,XXq- (n = 3); 46,XX/46,XXp- (n = 2); 46,Xi(Xq) (n = 2); 45,X/46,Xi(Xq) (n = 2); 46,XXp- (n = 1); 46,XX/47,XXX (n = 1); 46,XXq- (n = 1); 45,X/46,X(ry) (n = 1). Karyotype/phenotype correlation showed the gradation of severity of clinical phenotype to be related to the number of X chromosomes. The highest somatic scores and the most severe clinical manifestations were noted in cases of pure 45,X Turner and the mildest in 46,XX/46,XX(str) mosaics or pure 46,XX, including hypergonadotrophic hypogonadism. Our findings revealed a dosage effect of the X chromosome on phenotype, thus confirming that partial X chromosome inactivation modifies somatic and pubertal development. Our results also support both the additive and interactive hypotheses of karyotype/phenotype correlation.     

219例应用重组人生长激素的矮小儿童随访调查

目的 随访哈尔滨地区应用重组人生长激素（rhGH）治疗的矮小儿童219例,探讨其应用rhGH时的年龄分布、应用时间、及副作用情况.方法 对已应用rhGH的219例不同原因矮小儿童,其中男147例（67.1%）,女72例（32.9%）,采用统一的调查表,通过查阅病案获取资料,进行随访.随访内容包括：开始应用rhGH时的年龄、应用时间及副作用情况.结果 不同原因矮小儿童开始用药年龄多在12岁以后,占70.3%;用药时间多在6个月以内,占全部患儿的67.1%,最长者是GHD和Turner综合征患儿,用药时间超过3年;rhGH副作用小.结论 哈尔滨地区应用rhGH的矮小儿童中,应用rhGH的起始年龄均偏大,影响疗效;由于依从性及经济原因,应用rhGH时间均较短;在规定剂量内,适应症者可以大胆使用.对矮小患儿应明确病因,给予尽早治疗.     

Blood pressure in adults with short stature skeletal dysplasias

Hypertension, compounded by obesity, contributes to cardiovascular disease and mortality. Data describing hypertension prevalence in adults with short stature skeletal dysplasias are lacking, perhaps due to poor fit of typical adult blood pressure cuffs on rhizomelic or contracted upper extremities. Through health screening research, blood pressure was measured in short stature adults attending support group meetings and skeletal dysplasia clinics. Blood pressure was measured with a commercially available, narrower adult cuff on the upper and/or lower segment of the arm. Height, weight, age, gender, diagnosis, exercise, and medications were collected. Subjects were classified as normotensive, prehypertensive, or hypertensive for group analysis; no individual clinical diagnoses were made. In 403 short stature adults, 42% were hypertensive (systolic >140, diastolic >90 OR taking antihypertensive medications). For every BMI unit and 1 kg weight increase in males, there was a 9% and an 8% increase, respectively, in the odds of hypertension versus normotension. In females, the increase was 10% and 6%, respectively. In those with achondroplasia, the most common short stature dysplasia, males (n = 106) had 10% greater odds of hypertension versus normotension for every BMI unit and kilogram increase. In females with achondroplasia (n = 128), the odds of hypertension versus normotension was 8% greater for each BMI unit and 7% for each additional kilogram. These data suggest a high population prevalence of hypertension among short stature adults. Blood pressure must be monitored as part of routine medical care, and measuring at the forearm may be the only viable clinical option in rhizomelic short stature adults with elbow contractures.     

A Noonan-like short stature syndrome with sparse hair.

Noonan's syndrome is a clinically recognisable short stature syndrome with autosomal dominant inheritance. The diagnosis can be difficult as the phenotypic expression is very variable. There has been an attempt to divide this syndrome into type I (in which the facial features, especially ptosis, antimongoloid eye slant, and hypertelorism are prominent) and type II (where cardiological abnormalities are more to the fore), but this has not yet been confirmed by other studies.     

An unknown spondylo-meta-epiphyseal dysplasia in sibs with extreme short stature

In three sibs of Jordanian descent a unique type of severe spondylo-meta-epiphyseal dysplasia results in extreme disproportionate dwarfism. They have a distinct facial appearance with hypotelorism, prognathia, and hypodontia. The limbs are short and the hands and feet stubby. Radiologically, the irregular end plates of the vertebral bodies, the very small and late appearing epiphyseal ossification centres, and the hypoplastic acetabular roofs are most impressive. Histopathologic studies of the growth plate demonstrate characteristic findings with fingerprint-like inclusion bodies in the hypertrophic chondrocytes. This seems to be a distinct, autosomal recessive skeletal dysplasia. © 1996 Wiley-Liss, Inc.     

Biosynthetic human growth hormone in three children with short stature

Three boys with growth hormone deficiency were given biosynthetic human growth hormone, four units subcutaneously three times weekly, over two years. All three exceeded their expected growth velocities for bone age during the first year, but fared less well during the second year. Mean yearly growth velocities were: 3.2 cms before treatment, 7.1 cms after 12 months' treatment and 4.9 cms after a further 12 months. There were no adverse reactions.     

High incidence of SHOX anomalies in individuals with short stature

Objective

To study the SHOX gene and the PAR1 region in individuals with short stature.

Methods

The study involved 56 cases of dyschondrosteosis and 84 cases of idiopathic short stature (ISS). The study was designed to determine the following: the prevalence of SHOX anomalies in ISS; the frequency of Madelung deformity in individuals with SHOX anomalies; and the value of a family history of short stature in deciding whether to test for the SHOX gene.

Results

54 SHOX anomalies were observed, including 42 (68%) in the dyschondrosteosis group and 12 (15%) in the ISS group. The high frequency of SHOX anomalies in the ISS group can be explained by the large proportion of boys in this group, reflecting the difficulty in diagnosing dyschondrosteosis in young boys. Clinical evidence of Madelung deformity in six parents of ISS individuals emphasised the importance of family evaluation. Among the 54 SHOX anomalies, 33 PAR1 deletions were identified encompassing the SHOX gene (62%), one partial intragenic deletion (2%), nine deletions located downstream of the SHOX gene (16%), and 11 point mutations (20%).

Conclusions

These data emphasise the value of using microsatellite markers located within and downstream of the SHOX gene.     

New autosomal recessive syndrome with short stature and facio-auriculo-thoracic malformations

Two sibs, a boy and a girl, from a Lebanese consanguineous family presented with short stature, microcephaly, ptosis, small, dysplastic, low set ears, short neck, and pectum excavatum and carinatum. In addition, the boy had a high arched palate, a cardiac malformation, and at the X-rays an absence of fusion of the posterior hemi-arches of C7 and a fusion between L5 and S1 with a sagittal-cleft vertebral body of L5, while his sister had a cleft lip/palate and at the X-rays an abnormal odontoid peg and a malformation of the articular facets between C1 and C2, and bilateral cervical ribs. Other laboratory and radiological investigations were normal. Sequencing of PTPN11 exons 2, 3, 4, 7, 8, 12, and 13 did not reveal any variations. Two other sibs presented almost the same dysmorphic features; one girl died at age 6(1/4) years after an acute episode of renal insufficiency, and one boy died at 40 days of age. Differential diagnosis is discussed and the possibility of the report of a new autosomal recessive syndrome with variable expressivity is raised.     

Biallelic mutations in RTTN are associated with microcephaly,short stature and a wide range of brain malformations

Biallelic mutations in the RTTN gene have been reported in association with microcephaly, short stature, developmental delay and malformations of cortical development. RTTN mutations have previously shown to link aberrant ciliary function with abnormal development and organization of the human cerebral cortex. We here report three individuals from two unrelated families with novel mutations in the RTTN gene. The phenotype consisted of microcephaly, short stature, pachygyria or polymicrogyria, colpocephaly, hypoplasia of the corpus callosum and superior vermis. These findings provide further confirmation of the phenotype related to pathogenic variants in RTTN.