Home About us Contact
|
Home About us Contact | ||
|
|
||
Short Stature (short + stature)
Kinds of Short Stature Selected AbstractsAbnormal growth in mitochondrial diseaseACTA PAEDIATRICA, Issue 3 2009S Wolny Abstract Aim: To review the height and weight of children with mitochondrial disease attending our supra-regional service. Methods: This was a retrospective audit of cross-sectional data. Height and weight measurements were available in 24 children and adolescents (median 7.86 years; range 1.76,20.5 years) who all had a confirmed diagnosis of mitochondrial disease. Values were converted to SD scores using UK reference data. Results: Patients with mitochondrial disease were short with an overall SD score of ,1.97 (95% confidence intervals ,2.72 to ,1.23 SD). Patients were also thin with a relatively low BMI SDS of ,1.07 (95% confidence intervals ,1.69 to - 0.07 SD), which fell with advancing years (r =,0.7; p < 0.000). Conclusion: Short stature and a progressive reduction in body mass index (BMI) are features of mitochondrial disease in childhood. The mechanisms underlying the abnormal growth in these patients need to be studied in more detail. [source] Expanding the phenotypic spectrum of Caffey diseaseCLINICAL GENETICS, Issue 3 2007K Suphapeetiporn Infantile cortical hyperostosis (ICH) is an inherited disorder characterized by hyperirritability, acute inflammation of soft tissues, and massive subperiosteal new bone formation. It typically appears in early infancy and is considered a benign self-limiting disease. We report a three-generation Thai family with ICH, the oldest being a 75-year-old man. A heterozygous mutation for a 3040C,T in exon 41 of COL1A1 was found in affected individuals, further confirming the autosomal dominance of Caffey disease that is caused by this particular mutation. The novel findings in our studies include short stature and persistent bony deformities in the elderly. The height mean Z-score of the five affected individuals was ,1.75, compared to 0.53 of the other seven unaffected individuals giving a p-value of 0.008. Short stature may be partly due to progressive height loss from scoliosis, compression fractures of the spine and genu varus. These features, which have not previously been described, expand the phenotypic spectrum of the Caffey disease. [source] Growth hormone in short children: beyond medicine?ACTA PAEDIATRICA, Issue 1 2001LLE Bolt The indications for growth hormone (GH) treatment in non-GH-deficient short children are in debate, with some arguing that this treatment does not belong solely in the medical domain. We describe three different approaches to the issue, and argue that neither a disease-oriented nor client-oriented approach is sufficient. Both lead to withdrawal of medical interventions or to an undesirable application. Conclusion: An approach focusing on suffering as an indication for treatment of short stature is the most appropriate. The challenge is to develop proper tools by which to evaluate suffering and the efficacy of GH treatment in these children in order to relieve or prevent suffering. [source] Congenital Cardiovascular Disease in Turner SyndromeCONGENITAL HEART DISEASE, Issue 1 2008Carolyn A. Bondy MD ABSTRACT Turner syndrome (TS), or monosomy X, occurs in ,1/2000 live born females. Intelligence is normal and short stature is the most obvious and consistent feature of the syndrome. Congenital cardiovascular disease affects ,50% of individuals and is the major cause of premature mortality in adults. Unfortunately, this most important aspect of the syndrome has received little attention outside of pediatric medicine, and adult cardiological follow-up is seriously lacking. This review describes the spectrum of cardiovascular defects with particular attention to identifying risk factors for aortic dissection/rupture. X-chromosome genetic pathways implicated in Turner cardiovascular disease, including premature coronary artery disease, are discussed. Recent guidelines for diagnosis and treatment of girls and women with TS are reviewed. [source] Type I collagen is a genetic modifier of matrix metalloproteinase 2 in murine skeletal developmentDEVELOPMENTAL DYNAMICS, Issue 6 2007Mikala Egeblad Abstract Recessive inactivating mutations in human matrix metalloproteinase 2 (MMP2, gelatinase A) are associated with syndromes that include abnormal facial appearance, short stature, and severe bone loss. Mmp2,/, mice have only mild aspects of these abnormalities, suggesting that MMP2 function is redundant during skeletal development in the mouse. Here, we report that Mmp2,/, mice with additional mutations that render type I collagen resistant to collagenase-mediated cleavage to TCA and TCB fragments (Col1a1r/r mice) have severe developmental defects resembling those observed in MMP2 -null humans. Composite Mmp2,/,;Col1a1r/r mice were born in expected Mendelian ratios but were half the size of wild-type, Mmp2,/,, and Col1a1r/r mice and failed to thrive. Furthermore, composite Mmp2,/,;Col1a1r/r animals had very abnormal craniofacial features with shorter snouts, bulging skulls, incompletely developed calvarial bones and unclosed cranial sutures. In addition, trabecular bone mass was reduced concomitant with increased numbers of bone-resorbing osteoclasts and osteopenia. In vitro, MMP2 had a unique ability among the collagenolytic MMPs to degrade mutant collagen, offering a possible explanation for the genetic interaction between Mmp2 and Col1a1r. Thus, because mutations in the type I collagen gene alter the phenotype of mice with null mutations in Mmp2, we conclude that type I collagen is an important modifier gene for Mmp2. Developmental Dynamics 236:1683,1693, 2007. © 2007 Wiley-Liss, Inc. [source] Is treatment with growth hormone effective in children with cerebral palsy?DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 8 2004Melanie L Shim MD Children with cerebral palsy (CP) often have poor linear growth during childhood, resulting in a diminished final adult height. Here we report a female with CP and short stature but without growth hormone (GH) deficiency who exhibited increased growth during treatment with GH. We also report two other children with CP who were treated with GH: one female with a history of leukemia, and a male with Klinefelter syndrome. These two children were both found to be GH-deficient by insulin provocative GH testing and responded to treatment with increased growth rate. Growth improved to a greater extent in the two children with apparent GH deficiency. In summary, it is felt that GH therapy might be beneficial for children with CP and warrants further investigation. [source] Craniofacial morphology, dental occlusion, tooth eruption, and dental maturity in boys of short stature with or without growth hormone deficiencyEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 5 2000Heidrun Kjellberg The aim of this project was to study the craniofacial morphology, dental occlusion, dental maturation and tooth eruption in short-statured boys with growth hormone secretion ranging from low to high. The measurements from lateral and postero-anterior cephalograms, orthopantomograms and plaster models were used. Almost all linear measurements of the facial structures were significantly smaller. A disproportionate growth in the cranial base structures as well as in the jaws resulted in facial retrognathia, a proportionately smaller posterior than anterior facial height, and a steep vertical inclination of the mandible. Dental crowding was more common and the overbite was small. Dental maturity and tooth eruption were delayed 1.2 and 1.3 yr, respectively. No significant differences between the idiopathic short-statured and the growth hormone-deficient group in any of the above-mentioned variables were found. It can be concluded that although most of the cephalometric variables measured differed significantly from the average, the facial appearance of the boys is not conspicuous and is of minor clinical importance. However, the short-statured boys might be in greater need of orthodontic treatment due to the higher percentage of dental crowding. [source] Genotype differences in cognitive functioning in Noonan syndromeGENES, BRAIN AND BEHAVIOR, Issue 3 2009E. I. Pierpont Noonan syndrome (NS) is an autosomal-dominant genetic disorder associated with highly variable features, including heart disease, short stature, minor facial anomalies and learning disabilities. Recent gene discoveries have laid the groundwork for exploring whether variability in the NS phenotype is related to differences at the genetic level. In this study, we examine the influence of both genotype and nongenotypic factors on cognitive functioning. Data are presented from 65 individuals with NS (ages 4,18) who were evaluated using standardized measures of intellectual functioning. The cohort included 33 individuals with PTPN11 mutations, 6 individuals with SOS1 mutations, 1 individual with a BRAF mutation and 25 participants with negative, incomplete or no genetic testing. Results indicate that genotype differences may account for some of the variation in cognitive ability in NS. Whereas cognitive impairments were common among individuals with PTPN11 mutations and those with unknown mutations, all of the individuals with SOS1 mutations exhibited verbal and nonverbal cognitive skills in the average range or higher. Participants with N308D and N308S mutations in PTPN11 also showed no (or mild) cognitive delays. Additional influences such as hearing loss, motor dexterity and parental education levels accounted for significant variability in cognitive outcomes. Severity of cardiac disease was not related to cognitive functioning. Our results suggest that some NS-causing mutations have a more marked impact on cognitive skills than others. [source] One gene, two phenotypes: ROR2 mutations in autosomal recessive Robinow syndrome and autosomal dominant brachydactyly type B,HUMAN MUTATION, Issue 1 2003Ali R. Afzal Abstract Autosomal recessive Robinow syndrome (RRS) is a severe skeletal dysplasia with short stature, generalized limb shortening, segmental defects of the spine, brachydactyly, and a dysmorphic facial appearance. The gene encoding receptor orphan receptor tyrosine kinase 2 (ROR2) is located on chromosome 9q22 and homozygous loss-of-function mutations in this gene are responsible for RRS. Moreover, knocking out the mouse Ror2 gene causes mesomelic dwarfism in the homozygous state, with almost identical features to recessive Robinow syndrome. The protein product of this gene is a cell membrane receptor, containing distinct motifs including an immunoglobulin-like (Ig) domain, a Frizzled-like cysteine-rich domain (FRZ or CRD), and a kringle domain (KD) in the extracellular region; and an intracellular region with tyrosine kinase (TK), serine/threonine-rich, and proline-rich structures. The extracellular motifs of the ROR2 protein are known to be involved in protein,protein interactions. The tyrosine kinase domain is involved in an as yet uncharacterized signaling pathway. Interestingly, heterozygous mutations in ROR2 have recently been shown to give rise to autosomal dominant brachydactyly type B1 (BDB1). This condition is characterized by terminal deficiency of fingers and toes. A variety of mutations have been reported in ROR2. Here, these genetic defects are compiled and possible genotype,phenotype correlations are discussed. Hum Mutat 22:1,11, 2003. © 2003 Wiley-Liss, Inc. [source] Associations Between Baseline Risk Factors and Vertebral Fracture Risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) StudyJOURNAL OF BONE AND MINERAL RESEARCH, Issue 5 2004Olof Johnell Abstract Different risk factors may influence the effectiveness of osteoporosis therapies. The interaction of 30 baseline risk factors and the effectiveness of raloxifene in the MORE study were assessed. The efficacy of raloxifene in reducing vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fractures. Introduction: The aim of this analysis was to determine the effect of different risk factors on the effectiveness of raloxifene to reduce vertebral fractures in the Multiple Outcomes of Raloxifene Evaluation (MORE) study using logistic regression models. Materials and Methods: The association was assessed using univariate analyses and a multivariate model between 30 potential risk factors at baseline and the risk of vertebral fractures after 3 years in the placebo group, as well as the interaction of risk factors with raloxifene therapy (at a dose of 60 or 120 mg/day). Results and Conclusions: In the univariate analysis of the placebo group, after adjusting for baseline lumbar spine BMD (LS BMD), short stature (odds ratio [OR] = 1.18), age (OR = 1.38), years since menopause (OR = 1.38), impaired cognitive function, visuospatial capabilities (OR = 1.19), impaired musculoskeletal strength (OR = 1.23), low femoral neck BMD (OR = 1.21), and prior vertebral fracture (OR = 4.95) were significantly associated with the incidence of new vertebral fractures. In the univariate analysis, significant interactions were observed between raloxifene treatment and age (p = 0.04), serum triglycerides (p = 0.03), LS BMD (p = 0.08), and diabetes mellitus (p = 0.04). In the multivariate analysis, the effectiveness of raloxifene was independent of almost all risk factors, with the exception of baseline serum triglyceride level and LS BMD, suggesting an increased efficacy of raloxifene in patients with increased triglyceride levels (p = 0.006) and lower LS BMD values (p = 0.008) at baseline. These data suggest that the efficacy of raloxifene in reducing vertebral fractures is largely independent of the presence of clinical risk factors for osteoporotic fractures. [source] Positive Linear Growth and Bone Responses to Growth Hormone Treatment in Children With Types III and IV Osteogenesis Imperfecta: High Predictive Value of the Carboxyterminal Propeptide of Type I Procollagen,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2003Joan C Marini MD Abstract Extreme short stature is a cardinal feature of severe osteogenesis imperfecta (OI), types III and IV. We conducted a treatment trial of growth hormone in children with OI and followed linear growth velocity, bone metabolism markers, histomorphometrics, and vertebral bone density. Twenty-six children with types III and IV OI, ages 4.5,12 years, were treated with recombinant growth hormone (rGH), 0.1,0.2 IU/kg per day for 6 days/week, for at least 1 year. Length, insulin-like growth factor (IGF-I), insulin-like growth factor binding protein (IGFBP-3), bone metabolic markers, and vertebral bone density by DXA were evaluated at 6-month intervals. An iliac crest biopsy was obtained at baseline and 12 months. Approximately one-half of the treated OI children sustained a 50% or more increase in linear growth over their baseline growth rate. Most responders (10 of 14) had moderate type IV OI. All participants had positive IGF-I, IGFBP-3, osteocalcin, and bone-specific alkaline phosphatase responses. Only the linear growth responders had a significant increase in vertebral DXA z-score and a significant decrease in long bone fractures. After 1 year of treatment, responders' iliac crest biopsy showed significant increases in cancellous bone volume, trabecular number, and bone formation rate. Responders were distinguished from nonresponders by higher baseline carboxyterminal propeptide (PICP) values (p < 0.05), suggesting they have an intrinsically higher capacity for collagen production. The results show that growth hormone can cause a sustained increase in the linear growth rate of children with OI, despite the abnormal collagen in their bone matrix. In the first year of treatment, growth responders achieve increased bone formation rate and density, and decreased fracture rates. The baseline plasma concentration of PICP was an excellent predictor of positive response. [source] Preonset Studies of Spondyloepiphyseal Dysplasia Tarda Caused by a Novel 2-Base Pair Deletion in SEDL Encoding Sedlin,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2001Steven Mumm Abstract Spondyloepiphyseal dysplasia tarda (SEDT), an X-linked recessive skeletal disorder, presents with disproportionate short stature and "barrel-chest" deformity in affected (hemizygous) adolescent boys. In four reported families to date, mutations in a gene designated SEDL (spondyloepiphyseal dysplasia late) cosegregate with SEDT. We diagnosed SEDT in a short-stature, kyphotic 15-year-old boy because of his characteristic vertebral malformations. Clinical manifestations of SEDT were evident in at least four previous generations. A novel 2-base pair (bp) deletion in exon 5 of SEDL was found in the propositus by polymerase chain reaction (PCR) amplification and sequencing of all four coding exons. The mutation ATdel241-242 cosegregated with the kindred's skeletal disease. The deletion is adjacent to a noncanonical splice site for exon 5 but does not alter splicing. Instead, it deletes 2 bp from the coding sequence, causing a frameshift. A maternal aunt and her three young sons were investigated subsequently. Radiographs showed subtle shaping abnormalities of her pelvis and knees, suggesting heterozygosity. X-rays of the spine and pelvis of her 8-year-old son revealed characteristic changes of SEDT, but her younger sons (aged 6 years and 3 years) showed no abnormalities. SEDL analysis confirmed that she and only her eldest boy had the 2-bp deletion. Molecular testing of SEDL enables carrier detection and definitive diagnosis before clinical or radiographic expression of SEDT. Although there is no specific treatment for SEDT, preexpression molecular testing of SEDL could be helpful if avoiding physical activities potentially injurious to the spine and the joints proves beneficial. [source] A review of nutrition in Duchenne muscular dystrophyJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 5 2009Z. E. Davidson Abstract Duchenne muscular dystrophy (DMD) is a recessive X linked genetic disorder characterised by progressive muscle weakness and reduced muscle tone. Affecting only boys, it limits life expectancy to approximately 20 years. A literature review was conducted using MEDLINE and the Cochrane Library, employing the term ,Duchenne muscular dystrophy'. A total of 1491 articles in English were recovered. These papers were searched thematically under the headings: body composition (n = 10), energy expenditure (n = 10), nutrition (n = 6), corticosteroid therapy (n = 55) and gene therapy (n = 199). Key dietetic practice points were identified relevant to nutritional management. Papers supporting these key themes were assigned a level of evidence and grade of recommendation. There is limited high-quality evidence to guide the nutritional management of boys with DMD. Currently, the majority of evidence is based on expert opinion and clinical expertise. Delayed growth, short stature, muscle wasting and increased fat mass are characteristics of DMD and impact on nutritional status and energy requirements. The early introduction of steroids has altered the natural history of the disease, but can exacerbate weight gain in a population already susceptible to obesity. Prior to commencing steroids, anticipatory guidance for weight management should be provided. Malnutrition is a feature of end stage disease requiring a multidisciplinary approach, such as texture modification and supplemental feeding. Micronutrient requirements are yet to be determined but, as a result of corticosteroid treatment, vitamin D and calcium should be supplemented. Some evidence exists supporting supplementation with creatine monohydrate to improve muscle strength. More research is needed to provide a higher quality of evidence for dietitians working within this area. [source] A15. Public attitudes towards the healthiness of fruit juicesJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 5 2000K. I. France Background Fruit juice is a major part of children's diets and accounts for a large proportion of their fruit and vegetable servings. People may confuse fruit juice with fruit drinks. This can cause problems as people could possibly substituting a portion of fruit for a drink, which contains little or no fruit. Studies have shown that excessive consumption of fruit juice can lead to health problems in children, including short stature, obesity, nonorganic failure to thrive and carbohydrate malabsorption. An increase in dental erosion has also been noted which appears to correlate with an increase in fruit juice and carbonated beverage consumption. Aims The aim of this study was to find out what the general public's attitudes are towards the healthiness of fruit juice. Methods A mini focus group and a questionnaire were the methods used for data collection. The subjects were parents of children aged 12 or under in a local primary school. Results Overall, the study group had a poor knowledge of the difference between fruit juice and drinks, and knowledge of sugar content was poor. The group had a good knowledge of fruit content. Fruit juice was regarded as being a health drink. They were unsure if excessive consumption could damage children's health or not. Their main concern was regarding their children's teeth. The factor identified as being most influential when choosing a drink was flavour, followed closely by healthiness. Nutritional knowledge was generally poor. The average daily intake of juice was 650 mL (22.8 floz), considerably more than the value recommended by several experts. Conclusion There is a need for nutritional education regarding the consumption of fruit juice. The public should be made more aware of the potential problems associated with excessive fruit juice consumption without discouraging fruit juice intake altogether, as it is an important source of fruit in the diets of young children. [source] Pituitary mRNA Expression of the Growth Hormone Axis in the 1-Year-Old Intrauterine Growth Restricted RatJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2006T. Prins Intrauterine growth restriction (IUGR) is one of the major causes of short stature in childhood. Abnormalities in the growth hormone (GH) axis have frequently been observed in children who are born intrauterine growth restricted and GH treatment is effective to improve final height. However, the way that the GH axis is involved is not fully understood. Previously, when investigating the effect of IUGR on the central somatotrophic axis, a hypothalamic effect was discovered with elevated somatostatin and decreased neuropeptide Y mRNA expression levels, whereas serum GH and insulin-like growth factor I (IGFI) were unaltered. These findings were thought to indicate a hypothalamic alteration of the GH axis due to IUGR, probably to compensate pituitary output, thereby normalising peripheral values of GH and IGFI. Therefore, the present study aimed to evaluate the effect of IUGR on the pituitary GH axis in this rat model. Pups from rats that underwent bilateral uterine artery ligation at day 17 of pregnancy were studied. Pituitary glands were collected from 1-year-old offspring for quantitative measurements of GH, GH-receptor (GH-R), GH-releasing hormone receptor (GHRH-R), somatostatin receptor subtype 2 and 5, IGFI and IGFI receptor mRNA levels using a real-time reverse transcriptase-polymerase chain reaction. In addition, liver GH-R and IGFI mRNA expression levels were measured and a radioimmunoassay was performed to determine serum IGFI levels. In the IUGR rat, levels of pituitary GH, GH-R and GHRH-R relative gene expression (RGE) were increased. No differences were found in the RGE level of all other pituitary growth factors, liver GH-R and IGFI, and serum IGFI concentration between IUGR and control rats. The present data show that intrauterine growth failure leads to changes in the pituitary that might counterbalance the effects found previously in the hypothalamus. [source] Precocious puberty in Turner syndromeJOURNAL OF PAEDIATRICS AND CHILD HEALTH, Issue 11 2007Matthew A Sabin Abstract: Turner syndrome (TS) affects approximately 1 in 2000 liveborn girls. It is a common cause of short stature and is often, but not universally, associated with characteristic dysmorphic features and ovarian dysgenesis. Genotype/phenotype correlation in TS is generally poor and girls with TS may occasionally have normal functioning ovarian tissue, with approximately 30,40% entering puberty, 4% achieving menarche and 1% being fertile. In this report, we describe a girl with mosaic TS who unusually experienced spontaneous precocious puberty with associated accelerated longitudinal growth during mid childhood. This case acts as a useful clinical vignette with which to highlight important aspects of diagnosis and treatment in children with TS, particularly in relation to future growth potential and issues relating to fertility. [source] Increased melatonin concentrations in children with growth hormone deficiencyJOURNAL OF PINEAL RESEARCH, Issue 2 2007Michal Karasek Abstract:, A relationship between melatonin and growth hormone (GH) is poorly understood. We compare circadian melatonin rhythms in short children with normal and decreased GH secretion. The analysis included 22 children (20 boys and 2 girls) aged 11.1,16.9 yr (mean ± S.E.M. = 14.1 ± 0.3 yr) with short stature (height SDS below ,2.0). Based on the GH peak in stimulation tests patients were divided into two groups: idiopathic short stature (ISS, n = 11; GH peak , 10 ng/mL) and GH deficiency (GHD, n = 11; GH peak < 10 ng/mL). In all patients the circadian melatonin rhythm was assessed on the basis of nine blood samples, collected in 4-hr intervals during the daytime and 2-hr intervals at night, with dark period lasting from 22:00 to 06:00 hr. Magnetic resonance imaging examination excluded organic abnormalities in central nervous system in all patients. Melatonin concentration at 24:00, 02:00 and 04:00 hr as well as the area under curve of melatonin concentrations (AUC) were significantly higher in the patients with GHD than in individuals with ISS. Significant correlations between GH secretion and melatonin concentrations at 24:00, 02:00 and 04:00 hr, and AUC were also observed. On the basis of these data it seems that the assessment of nocturnal melatonin secretion might be a valuable diagnostic tool used for the improvement of the difficult diagnosis of short stature in children. [source] Rare case of Alstrom syndrome without obesity and with short stature, diagnosed in adulthood (Case Report)NEPHROLOGY, Issue 2 2006EYUP KOÇ SUMMARY: Alstrom syndrome is a rare autosomal recessive disorder characterized by retinal degeneration, sensorineural hearing loss, obesity, type 2 diabetes mellitus and chronic nephropathy. It may be associated with acanthosis nigricans, hypergonadotropic hypogonadism, hepatic dysfunction, hepatic steatosis, hyperlipidaemia, dilated cardiomyopathy and short stature. We report a patient with Alstrom syndrome who had hypergonadotropic hypogonadism, hepatic dysfunction, hepatic steatosis and short stature with normal body weight, all of which are seen infrequently with this syndrome. [source] Pigmented Hypertrichotic Dermatosis and Insulin Dependent Diabetes: Manifestations of a Unique Genetic Disorder?PEDIATRIC DERMATOLOGY, Issue 2 2007F.A.C.D., Julie Prendiville M.B. Three patients were the offspring of consanguineous parents. All four boys had pigmented hypertrichotic patches or induration on the upper inner thighs, with variable involvement of the genitalia, trunk, and limbs. Two boys had episcleritis and orbital proptosis with similar facies and musculoskeletal abnormalities including clinodactyly, flat feet, and short stature. One child had paraaortic and inguinal lymphadenopathy and three patients had an enlarged liver and spleen. A large, swollen pancreas was observed on ultrasound imaging in one patient with insulin dependent diabetes who also had echocardiographic evidence of pericardial inflammation. Three boys had elevated laboratory markers of inflammation. Biopsy specimens from the skin and orbit showed a chronic inflammatory cell infiltrate composed of polyclonal lymphocytes, histiocytes, and plasma cells; fibrosis was observed in two patients, one of whom had previously received radiation therapy to the orbit. Two boys responded to treatment with subcutaneous interferon- ,, combined with a short course of oral prednisone in the child without diabetes. We believe these inflammatory pigmented skin lesions represent a unique dermatosis associated with diabetes mellitus and systemic disease. The pathogenesis is unknown. The presence of consanguinity in three of four families, and similar dysmorphic features in two boys, suggest a genetic disorder, possibly with autosomal recessive inheritance. [source] Use of intrapulmonary percussive ventilation (IPV) in the management of pulmonary complications of an infant with osteogenesis imperfectaPEDIATRIC PULMONOLOGY, Issue 11 2009Gustavo Nino MD Abstract Osteogenesis imperfecta (OI) is a genetic disorder characterized by abnormal collagen formation and short stature. These patients present with frequent vertebral, rib, and long bone fractures. There are many respiratory complications associated with OI including pneumonia, the most common cause of mortality in the severe forms of the disease. We present a case of an infant with OI (type III/IV) and significant tracheobronchomalacia who had required multiple hospitalizations for recurrent atelectasis and respiratory failure in the setting of acute respiratory infections. External chest percussion and vibration were avoided because of the risk of rib fractures. intrapulmonary percussive ventilation (IPV) was initiated during an acute illness with good effect, and continued successfully after discharge from hospital. We conclude that IPV represents a safe and effective alternative to airway clearance in infants with OI. Pediatr Pulmonol. 2009; 44:1151,1154. ©2009 Wiley-Liss, Inc. [source] Liver transplantation for progressive familial intrahepatic cholestasis: Clinical and histopathological findings, outcome and impact on growthPEDIATRIC TRANSPLANTATION, Issue 6 2007Sema Aydogdu Abstract:, In this study, we analyze the demographic features, clinical and histopathological findings in patients who underwent liver transplantation for progressive familial intrahepatic cholestasis. We also analyze outcome and impact of liver transplantation on growth and bone mineral content. Most of the patients were presented with jaundice mainly beginning within the first six months. At the time of initial admission; eight patients had short stature (height SD score <2), and four patients had weight SD score <2. Liver transplantation were performed at the age of 43.2 ± 27 months (range 9 to 96 mfonths), 6.5 ± 3.5 months later after the first admission. Infection, surgical complications and osmotic diarrhea associated with severe metabolic acidosis were noted in 41.4%, 16.6% and 33.3%, respectively. One patient developed posttransplant lymphoproliferative disorder. Overall; 1 year graft and patient survival was 69.2% and 75%, respectively. At the end of the 1st year only 2 patients had height SD score <2. Linear regression of height gain against increase in total body BMD measured at the time of transplantation and 1 year after liver transplantation gave a coefficient r = 0.588 (p = 0.074). No correlation was found between the height gain and age and PELD score at time of transplantation, and no difference was noted between the sexes and donor type. Liver transplantation is effective treatment modality with good outcome and little morbidity, and increases the growth acceleration in patients with PFIC associated with cirrhosis. [source] Turner syndrome phalangeal screening based on a two-stage linear regression conceptPEDIATRICS INTERNATIONAL, Issue 4 2009Chui-Mei Tiu Abstract Background:, Turner syndrome (TS) is a congenital chromosomal abnormality, resulting in short stature, short fourth metacarpal, and retarded skeletal maturation in children. The existing methods of diagnosis, which include carpal angle, metacarpal sign, and body mass index (BMI), cannot accurately diagnose TS. The authors propose a novel procedure for examining the hand skeleton to distinguish between normal individuals and patients with TS. Methods:, This investigation was divided into two parts. In the first part, existing methods (evaluation of the metacarpal sign, measurement of the carpal angle, and determination of BMI) were used. Examination in the second part was based on the two-stage screening method (TSSM). In the first stage in TSSM, the ratio of the lengths of the distal,middle phalanges of the fifth digit was determined in normal subjects with average range of satisfactory body height and TS patients. A suitable cut-off was found on linear regression and used to divide the plot into TS patients and normal subjects. In the second stage, the normal section was transferred to another group based on bone and chronological ages. A greater number of patients were diagnosed with TS using this method. Finally, four cut-off parameters were determined on linear regression analysis. Results with optimal sensitivity and specificity were automatically obtained. Results:, The combination of TSSM with optimal programming (sensitivity = 0.81 and specificity = 0.91) was satisfactory for diagnosing TS patients. Conclusion:, TSSM can suitably evaluate growth of the hand skeleton to distinguish between normal individuals and patients with TS. [source] Growth patterns in early childhood and final attained stature: Data from five birth cohorts from low- and middle-income countries,AMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2010Aryeh D. Stein Growth failure is cumulative, and short stature is associated with multiple indices of reduced human capital. Few studies have been able to address in a single analysis both consideration of the timing of growth failure and comparison across populations. We analyzed data from birth cohorts in Brazil, Guatemala, India, the Philippines, and South Africa (n = 4,659). We used data on length at birth (available for three of the five cohorts), 12 mo, 24 mo, and mid-childhood to construct cohort- and sex- specific conditional length measures. We modeled adult height as a function of conditional length in childhood. The five cohorts experienced varying degrees of growth failure. As adults, the Brazil sample was 0.35 ± 0.89 standard deviations (SD) below the World Health Organization reference, while adult Guatemalans were 1.91 ± 0.87 SD below the reference. All five cohorts experienced a nadir in height for age Z -score at 24 mo. Birth length (in the three cohorts with this variable), and conditional length at 12 mo (in all five cohorts) were the most strongly associated with adult height. Growth in the periods 12,24 mo and 24 mo to mid-childhood showed inconsistent patterns across tertiles of adult height. Despite variation in the magnitude of cumulative growth failure across cohorts, the five cohorts show highly consistent age-specific associations with adult stature. Growth failure prior to age 12 mo was most strongly associated with adult stature. These consistencies speak to the importance of interventions to address intrauterine growth failure and growth failure in the first 12 mo of life. Am. J. Hum. Biol. 2010. © 2009 Wiley-Liss, Inc. [source] Taller women do better in a stressed environment: Height and reproductive success in rural Guatemalan womenAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 3 2008Thomas V. Pollet Previous research on the relationship between height and reproductive success in women has produced mixed results. One possible explanation for these is mediation by ecological factors, such as environmental stress. Here we investigate female height and reproductive success under conditions of environmental stress (poverty) using a large scale dataset from Guatemala (n = 2,571). Controlling for educational attainment, age and ethnicity, we examined relationships between height and childlessness, occurrence of a stillbirth, fertility and child survival. There was no significant relationship between height and never haven given birth. Extremely short women had a significantly raised likelihood of experiencing stillbirth. There were curvilinear relationships between height and age at first birth, fertility, and survival rates for children. Overall, though, the penalties for short stature, particularly in terms of child survival, were far greater than those associated with extreme tallness, and so female height is positively associated with overall fitness in this population. Am. J. Hum. Biol., 2008. © 2008 Wiley-Liss, Inc. [source] Update on the clinical features and natural history of Wolf,Hirschhorn (4p-) syndrome: Experience with 87 patients and recommendations for routine health supervision,AMERICAN JOURNAL OF MEDICAL GENETICS, Issue 4 2008Agatino Battaglia Abstract Wolf,Hirschhorn syndrome (WHS) is a well-known multiple congenital anomalies/mental retardation syndrome, firstly described in 1961 by Cooper and Hirschhorn. Its frequency is estimated as 1/50,000,1/20,000 births, with a female predilection of 2:1. The disorder is caused by partial loss of material from the distal portion of the short arm of chromosome 4 (4p16.3), and is considered a contiguous gene syndrome. No single gene deletions or intragenic mutations have been shown to confer the full WHS phenotype. Since the disorder was brought to the attention of geneticists, many additional cases have been published. Only in 1999, however, were the first data on the natural history brought to the attention of the medical community. The purpose of the present study is to help delineate in more detail and over a longer period of time, the natural history of WHS, in order to establish appropriate health supervision and anticipatory guidance for individuals with this disorder. We have collected information on 87 patients diagnosed with WHS (54 females and 33 males) both in USA and Italy. Age at first observation ranged between newborn and 17 years. Twenty patients have been followed from 4 months to 23 years. The deletion proximal breakpoint varied from 4p15.32 to 4p16.3, and, by FISH, was terminal and included both WHSCR. Deletion was detected by standard cytogenetics in 44/87 (50.5%) patients, whereas FISH was necessary in the other 43 (49.5%). Array-CGH analysis at 1 Mb resolution was performed in 34/87 patients, and, in 15/34 (44%), showed an unbalanced translocation leading to both a 4p monosomy and a partial trisomy for another chromosome arm. Six more patients had been previously shown to have an unbalanced translocation by karyotype analysis or FISH with a WHS-specific probe. Sixty-five of 87 patients had an apparent pure, de novo, terminal deletion; and 1/87 a tandem duplication of 4p16.1p16.3 associated with 4p16.3pter deletion. Age at diagnosis varied between 7 months gestation and 16 years. Ninety-three percent had a seizure disorder with a good outcome; 80% had prenatal onset growth deficiency followed by short stature and slow weight gain; 60% had skeletal anomalies; 50% had heart lesions; 50% had abnormal tooth development; and 40% had hearing loss. Distinctive EEG findings were seen in 90%. Structural CNS anomalies were detected in 80%. Global developmental delay of varying degrees was present in all patients. Almost 50% was able to walk either alone or with support. Hypotonia was present in virtually all patients. A global improvement was observed in all individuals, over time. Our survey has also shown how the characteristic facial phenotype tends to be less pronounced in those patients with a smaller deletion, and microcephaly is not observed in the patients with certain cryptic unbalanced translocations. © 2008 Wiley-Liss, Inc. [source] A familial Xp+ chromosome detected during fetal karyotyping, which is associated with short stature in four generations of a Turkish familyPRENATAL DIAGNOSIS, Issue 4 2003B. Karaman Abstract The short-stature homeobox-containing gene (SHOX) on chromosome Xp22.3 was recently identified as an important determinant of the stature phenotype. Deletions of the SHOX gene, some of them due to structural chromosome abnormalities, have been described in patients with idiopathic short stature and Leri-Weill syndrome. Additionally, haploinsufficiency of SHOX is a main cause for short stature seen in patients with Turner syndrome. Here we report an unusual X-chromosome abnormality, which was detected during a fetal karyotyping performed because of a previous child with Down syndrome. GTG banding demonstrated an extra chromosome segment on the terminal part of the short arm of chromosome X in the index case (karyotype: 46,X,Xp+). The same chromosomal abnormality was found in the mother and the maternal grandmother. All carriers of this chromosomal abnormality presented with short stature but no other associated symptoms. Whole chromosome painting of X revealed a homogeneous painting of the abnormal X chromosome indicating that no other chromosome was involved. Additional FISH studies with probe DXS1140 (Kallmann probe at Xp22.3), Quint-Essential X-Specific DNA (DMD probe at Xp21.2), XIST (at Xq13.2), and Tel Xq/Yq were performed, and no abnormality was observed in the intensities or the localizations of the probes signals. However, applying a specific SHOX gene probe (derived from cosmid LLNONO3M34F5) showed a loss of signal on the derivative X chromosome. Our results show that the Xp+ generation led to a deletion of the complete SHOX gene and caused short stature in the presented family. Copyright © 2003 John Wiley & Sons, Ltd. [source] Ring chromosome 6 in three fetuses: Case reports, literature review, and implications for prenatal diagnosisAMERICAN JOURNAL OF MEDICAL GENETICS, Issue 2 2002Maik Urban Abstract Prenatal and postnatal findings in three fetuses with a ring chromosome 6 are presented, and the literature of this rare cytogenetic disorder is reviewed. The described fetuses illustrate the broad spectrum of the clinical manifestation of ring chromosome 6. In one fetus, the disorder was diagnosed incidentally by a routine amniocentesis due to advanced maternal age. The other two fetuses were hydrocephalic and had other congenital anomalies. Remarkably, the ring chromosome 6 tends to disappear in cultured amniotic fluid cells; karyotyping revealed complete or nearly complete monosomy 6. In contrast, the ring was preserved in high proportions of fetal leukocytes. Postnatal growth retardation is the only consistent finding of this chromosomal disorder. Maternal age is not significantly above average. An additional review of 20 literature cases revealed a striking tendency to hydrocephalus, either due to deficient brain growth or secondary to an aqueductal stenosis. Children with hydrocephalus and ring chromosme 6 tend to display facial dysmorphism and may have additional malformations, growth failure, eye anomalies, and seizures. In contrast, there are two reports on children with a ring chromosome 6 who had short stature, normal appearance, and a normal or almost-normal psychomotor development. In such patients at the mild end of the clinical spectrum, the phenotype is basically restricted to what Kosztolányi. [1987: Hum Genet 75:174,179] delineated as "ring syndrome," comprising "severe growth failure without major malformations, without a specific deletion syndrome, with only a few or no minor anomalies, and mild to moderate mental retardation." This "ring syndrome" is considered to occur independently of the autosome involved in the ring formation. The overall impression from our cases and from the literature review of cases with ring chromosome 6 is that the karyotype-genotype correlation is poor. This makes prognostic counseling of parents difficult and unsatisfactory. Serial targeted ultrasound examinations, especially of the brain, are decisive factors in elucidating the prognosis. © 2002 Wiley-Liss, Inc. [source] Detection of norbolethone, an anabolic steroid never marketed, in athletes' urineRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 13 2002Don H. Catlin Norbolethone (13-ethyl-17-hydroxy-18,19-dinor-17,-pregn-4-en-3-one) is a 19-nor anabolic steroid first synthesized in 1966. During the 1960s it was administered to humans in efficacy studies concerned with short stature and underweight conditions. It has never been reported by doping control laboratories. Norbolethone was identified in two urine samples from one athlete by matching the mass spectra and chromatographic retention times with those of a reference standard. The samples also contained at least one likely metabolite. The samples were also unusual because the concentrations of endogenous steroids were exceptionally low. Since norbolethone is not known to be marketed by any pharmaceutical company, a clandestine source of norbolethone may exist. Copyright © 2002 John Wiley & Sons, Ltd. [source] Developmental and degenerative features in a complicated spastic paraplegiaANNALS OF NEUROLOGY, Issue 4 2010M. Chiara Manzini PhD Objective We sought to explore the genetic and molecular causes of Troyer syndrome, one of several complicated hereditary spastic paraplegias (HSPs). Troyer syndrome had been thought to be restricted to the Amish; however, we identified 2 Omani families with HSP, short stature, dysarthria and developmental delay,core features of Troyer syndrome,and a novel mutation in the SPG20 gene, which is also mutated in the Amish. In addition, we analyzed SPG20 expression throughout development to infer how disruption of this gene might generate the constellation of developmental and degenerative Troyer syndrome phenotypes. Methods Clinical characterization of 2 non-Amish families with Troyer syndrome was followed by linkage and sequencing analysis. Quantitative polymerase chain reaction and in situ hybridization analysis of SPG20 expression were carried out in embryonic and adult human and mouse tissue. Results Two Omani families carrying a novel SPG20 mutation displayed clinical features remarkably similar to the Amish patients with Troyer syndrome. SPG20 mRNA is expressed broadly but at low relative levels in the adult brain; however, it is robustly and specifically expressed in the limbs, face, and brain during early morphogenesis. Interpretation Null mutations in SPG20 cause Troyer syndrome, a specific clinical entity with developmental and degenerative features. Maximal expression of SPG20 in the limb buds and forebrain during embryogenesis may explain the developmental origin of the skeletal and cognitive defects observed in this disorder. ANN NEUROL 2010;67:516,525 [source] Premature arthritis is a distinct type II collagen phenotypeARTHRITIS & RHEUMATISM, Issue 5 2010Peter Kannu Mutations in the gene encoding type II collagen (COL2A1) give rise to a spectrum of phenotypes predominantly affecting cartilage and bone. These chondrodysplasias are typically characterized by disproportionately short stature, eye abnormalities, cleft palate, and hearing loss. It is less recognized that mutations in COL2A1 can also present as degenerative joint disease in the absence of any other phenotypic clues. We report 2 Australian families presenting with an isolated arthritis phenotype, segregating as a dominant trait affecting both large and small joints, prior to age 30 years. Sequencing of COL2A1 in the propositi revealed 2 sequence changes resulting in glycine substitutions in the triple-helical domain of type II collagen. We review the increasing evidence implicating COL2A1 mutations in individuals presenting with isolated degenerative joint disease, aiming to alert physicians who assess these patients to this possibility. The importance of finding a COL2A1 mutation in such patients lies in the subsequent ability to accurately assess recurrence risks, offer early (including prenatal) diagnosis, and provide information regarding the natural history of the condition. Most importantly, it enables at-risk individuals to be identified for implementation of preventative strategies (i.e., weight loss, joint-friendly exercise programs) and early ameliorative management of their condition. [source] | ||||||||||||||||||||||||||||