Cause Of Short Stature Research Articles

Changing Scenario in Aetiological Profile of Short Stature in India-Growing Importance of Celiac Disease: A Study from Tertiary Care Centre

To compare the etiological profile of short stature at a tertiary care hospital of North India over a decade from 1995-2007. Children attending the Post Graduate Institute of Medical Education and Research and also fulfilling the criteria for short stature over the two time periods of 1995-96 and 2005-07 were analyzed retrospectively for causes of short stature. The age group of children ranged from 10 to 15 years. Appropriate screening and definitive tests were performed to establish the etiology of short stature. In the year 1995-1996, 190 children with short stature were diagnosed. The common causes of short stature were primary hypothyroidism in 35(18.4%) followed by pituitary disorders in 29(15.2%) and nutritional disorders in 33(17.4%) while in year 2005-2007, 256 children were diagnosed with short stature. The etiology of short stature in these children were pituitary disorders in 51(19.2%) followed by celiac disease in 35(13.7%) and hypothyroidism in 35(13.7%) cases. In majority of celiac disease patients growth retardation was the presenting manifestation rather than gastrointestinal symptoms. Etiology of short stature significantly changed over a decade probably due to high index of suspicion and wide and better availability of screening tests for celiac disease. We propose all growth retarded children should be screened for celiac disease irrespective of gastrointestinal symptoms as well as periodic review of etiology of short stature.

Isolated Short Stature As a Presentation of Celiac Disease in Saudi Children

The aim of this study is to assess the prevalence of isolated short stature as a clinical presentation of celiac disease in Saudi Arab children and whether some of the routine laboratory tests performed to determine the cause of short stature could suggest the diagnosis of celiac disease. A total of 91 children with short stature were included in the study. Extensive endocrine and biochemical assessments, including total protein, serum albumin, calcium phosphate and alkaline phosphatase assays; renal function tests; coagulation profile; anti-endomysial antibodies and anti-tissue transglutaminase antibody, growth hormone, thyroid stimulating hormone, free-thyroxin (FT4) assays; stool tests for giardiasis; bone age; and endoscopic intestinal biopsies, were done for all children. Ten of the 91 children had positive intestinal biopsies in the form of total villous atrophy, an increase in crypt height, and an increase in intra-epithelial lymphocyte (IEL) numbers up to >40 IEL/100 EC (Type 3C) according to the Oberhuber classification, confirming the diagnosis of celiac disease. Five children had mild villous atrophy according to this classification (Type 3A), and they were considered to have potential celiac disease. Seventy-six children had normal intestinal biopsies. Therefore, the prevalence of celiac disease among Saudi children with short stature was 10.9%, and 4.3% of the children were diagnosed as having potential celiac disease. After confirming the diagnosis of celiac disease, all children were kept on a gluten-free diet and all of them showed improvement in their growth rate. We concluded that celiac disease is a very important cause of short stature in children without gastrointestinal complaints in Saudi Arabia. We highly recommend anti-tissue transglutaminase and anti-endomysial antibody screening tests, and a small bowel biopsy to confirm the diagnosis of celiac disease irrespective of the results of the antibody assays, in children with short stature in Saudi Arabia. Once the diagnosis is confirmed, children should be kept on a gluten-free diet so they can catch up their growth early before they develop permanent short stature.

The spectrum of clinical paediatric endocrinology: 28 years of referrals to an individual consultant

To review referrals throughout the career of an individual paediatric endocrinologist. A retrospective cohort study in metropolitan clinics in Queensland analysed details of all 9062 patients aged<18 years referred between January 1980 and December 2007 to determine the proportion of diagnoses in major disease categories and changes in referral patterns over time. Short stature (29%), type-1 diabetes mellitus (20%) and pubertal disorders (12%) accounted for most cases, with thyroid disorders (7%), obesity (6%), tall stature (5%) and hypothalamic-pituitary disorders (4%) the next commonest. An organic cause for short stature, early puberty, late puberty, tall stature and obesity was found in 39%, 32%, 19%, 15% and 6% of cases, respectively. Boys were more likely to present with short stature or delayed puberty, and girls with tall stature and early puberty. Substantially fewer boys than girls were diagnosed in infancy with congenital adrenal hyperplasia, suggesting that some may be dying undiagnosed. Comparisons between 1980 and 1984, and 2000-2004 revealed increases in the percentage of referrals for type-1 diabetes mellitus (particularly in the young), early puberty, hypothalamic-pituitary and bone disorders, and decreases in those for short and tall stature. Disorders of growth and puberty accounted for 52% of referrals and many have an organic cause. A neonatal screening programme for congenital adrenal hyperplasia is overdue. Changing attitudes to short and tall stature and a profound increase in new cases of diabetes mellitus indicate that substantially greater resources for treatment of childhood diabetes mellitus will be required in future.

Short stature in Saudi Arabia: Etiologic profile in adult endocrine clinic

To determine causes of short stature (SS) in adult endocrine service at a Saudi Arabian tertiary center. A retrospective analysis was made of data from 104 subjects who were primarily evaluated for causes of SS in the endocrinology unit of King Khalid University Hospital Riyadh from January 1 997 to December 2006. Growth hormone deficiency (GHD) and normal variant short stature (NVSS) were the leading causes of SS contributing 90 subjects (86%; 43% for each), followed by celiac disease in 4 subjects (4%). Other etiologies of short stature included primary hypothyroidism, diabetes mellitus, and Turner's syndrome (2% each). We conclude that GHD and NVSS are the commonest causes of SS in Saudi Arabia. In view of the need to differentiate the two major etiologies, it is suggested that growth hormone stimulatory tests be conducted on all patients with SS associated with delayed bone age. Further prospective study in a larger population is needed to characterize this finding.

Congenital Growth Hormone Deficiency - A Review with a Focus on Neuroimaging.

Growth hormone deficiency is an important cause of short stature in childhood. It is characterised by low growth velocity in childhood and is diagnosed by stimulation testing. Individuals with growth hormone deficiency may have other pituitary hormone deficits in addition to growth hormone deficiency. When multiple pituitary hormone deficiencies are present, abnormal pituitary anatomy, as visualised on magnetic resonance imaging (MRI), is a frequent finding. The classic triad (ectopic posterior pituitary, hypoplastic or aplastic anterior pituitary and absent/thin pituitary stalk) or variants of the classic triad are commonly seen in these patients. Volumetric sequencing allows all three planes of visualisation to be reconstructed in post-processing, allowing the radiologist to more fully evaluate pituitary anatomy. The normal dimensions of the pituitary gland vary by age and precise definitions of what constitutes a hypoplastic gland are not clearly defined in the medical literature. Having an experienced neuroradiologist interpret the MRI in patients with pituitary dysfunction is very important.

Enhancer deletions of the SHOX gene as a frequent cause of short stature: the essential role of a 250 kb downstream regulatory domain

Background:Mutations and deletions of the homeobox transcription factor gene SHOX are known to cause short stature. The authors have analysed SHOX enhancer regions in a large cohort of short stature...

Effectiveness of the Combined Recombinant Human Growth Hormone and Gonadotropin-Releasing Hormone Analog Therapy in Pubertal Patients with Short Stature due toSHOXDeficiency

Isolated heterozygous SHOX defects are the most frequent monogenic cause of short stature, and combined therapy with recombinant human GH (rhGH) and GnRH analog (GnRHa) in pubertal patients has been suggested, but there are no data on final height. The aim of the study was to analyze adult height after rhGH and GnRHa therapy in patients with SHOX haploinsufficiency. Ten peripubertal patients with isolated SHOX defects participated in the study. Five patients were followed without treatment, and five were treated with rhGH (50 mug/kg/d) and depot leuprolide acetate (3.75 mg/month). Adult height sd score (SDS) was measured. All patients followed without treatment had marked downward growth shift during puberty (height SDS, -1.2 +/- 0.7 at 11.4 +/- 1.4 yr; adult height SDS, -2.5 +/- 0.5). Conversely, four of five patients treated with rhGH for 2 to 4.9 yr associated to GnRHa for 1.4 to 5.8 yr improved their height SDS from -2.3 +/- 1.3 at 11.8 +/- 2.1 yr to a final height SDS of -1.7 +/- 1.6. The difference between the mean height SDS at the first evaluation and final height SDS was statistically significant in nontreated vs. treated patients (mean height SDS change, -1.2 +/- 0.4 vs. 0.6 +/- 0.4, respectively; P <0.001). A gain in adult height of patients with isolated SHOX defects treated with combined rhGH and GnRHa therapy was demonstrated for the first time, supporting this treatment for children with SHOX defects who have just started puberty to avoid the loss of growth potential observed in these patients during puberty.

Imaging ofSHOX-Associated Anomalies

Human growth is a multifactorial trait influenced by environmental, hormonal, and genetic factors. Although it is clear that multiple factors contribute to an individual's final height and limb development, genetic factors play a crucial role. One such gene is the short stature homeobox ( SHOX) containing gene. Knowledge about the SHOX gene has rapidly increased since its discovery in 1997, and we now know that SHOX haploinsufficiency affects the development of the extremities and is an important cause of short stature. Currently, SHOX mutations occur with an estimated incidence of roughly 1 in 1000 newborns, making mutations of this gene one of the most common genetic defects associated with growth failure and skeletal deformities. Heterozygous mutations of SHOX have been implicated in patients with Madelung's deformity, Leri-Weill dyschondrosteosis (77%), Turner's syndrome (66%), and idiopathic short stature (3%), and homozygous mutations of SHOX gene have been identified in patients with Langer's mesomelic dysplasia (100%). Recognition of the early radiographic features encountered in SHOX haploinsufficiency maybe pivotal for the diagnosis. In this article, we summarize the genetic and clinical features of the various SHOX haploinsufficiency-associated disorders. We present the characteristic imaging features of these disorders and the results of growth hormone treatment trials.

A 12 year old girl with acrodysostosis: a rare cause of short stature

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ACMG practice guideline: Genetic evaluation of short stature

Short stature is a common indication for genetic evaluation. The differential diagnosis is broad and includes both pathologic causes of short stature and nonpathologic causes. The purpose of genetic evaluation for short stature is to provide accurate diagnosis for medical management and to provide prognosis and recurrence risk counseling for the patient and family. There is no evidence-based data to guide the geneticist in an efficient, cost-effective approach to the evaluation of a patient with short stature. This guideline provides a rubric for the evaluation of short stature evaluation and summarizes common diagnoses and clinical testing available.

Prevalence of IGF1 deficiency in prepubertal children with isolated short stature

'Primary IGF1 deficiency (IGFD)' is defined by low levels of IGF1 without a concomitant impairment in GH secretion in the absence of secondary cause. The aims of this study were to evaluate the prevalence of non-GH deficient IGFD in prepubertal children with isolated short stature (SS) and to describe this population. This retrospective study included all children with isolated SS seen in our Pediatric Endocrinology Unit from January 2005 to December 2007. Children were included based on the following criteria: i) SS with current height SDS < or = -2.5, ii) age > or = 2 years, and iii) prepubertal status. Exclusion criteria were: i) identified cause of SS and ii) current or past therapy with rhGH. IGF1-deficient children were defined as children without GH deficiency and with IGF1 levels below or equal to -2 SDS. Among 65 children with isolated SS, 13 (20%) had low IGF1 levels, consistent with a diagnosis of primary IGFD, four of which were born small for gestational age and nine were born appropriate for gestational age. When compared with non-IGFD children, IGFD children had higher birth weight (-0.7 vs -1 SDS, P=0.02) and birth height (-1.7 vs -2 SDS, P=0.04) and more delayed bone age (2.6 vs 1.7 years, P=0.03). The prevalence of primary IGFD was 20% in children with isolated SS. Concerning the pathophysiology, our study emphasizes that IGFD in some children may be secondary to nutritional deficiency or to maturational delay.

Etiology of short stature in children.

To determine the causes of short stature in children with special emphasis on growth hormone deficiency. Case series. Department of Paediatrics, Military Hospital, Rawalpindi and Combined Military Hospital, Multan from September 2004 to January 2007. Two hundred and fourteen children (140 boys and 74 girls), ranging from 02 to 15 years presenting with short stature were studied. Height and weight were plotted on appropriate growth charts and centiles determined. Relevant hematological and biochemical investigations including thyroid profile were done. Bone age was determined in all cases. Growth hormone axis was investigated after excluding other causes. Karyotyping was done in selected cases. Data was analyzed by SPSS 10.0 by descriptive statistics. Mean values were compared using t-test. In this study, the five most common etiological factors in order of frequency were Constitutional Growth Delay (CGD), Familial Short Stature (FSS), malnutrition, coeliac disease and Growth Hormone Deficiency (GHD). In 37.4% of patients, the study revealed normal variants of growth - CGD, FSS or combination of both, 46.7% cases had nonendocrinological and 15.9% had endocrinological etiology. CGD (22.1%) in males and FSS (27%) in females were the most common etiology. GHD was found in 6.1% children and it comprised 38.2% of all endocrinological causes. Children with height falling below 0.4th centile were more likely to have a pathological short stature (79.2%) compared to 39.3% whose height was below 3rd centile but above 0.4th centile (p < 0.05). CGD and FSS are most common causes of short stature in boys and girls respectively, whereas, GHD is a relatively uncommon etiology.

Does every short stature child need screening for celiac disease?

To study the etiological profile of short stature at a tertiary care hospital in north India. In this prospective study, 176 children with short stature were enrolled from January 2005 to December 2006. Appropriate screening and definitive tests were performed to establish the etiology of short stature. Celiac disease (CD) emerged as the single most common (15.3%) cause of short stature, followed by various endocrine disorders. It was interesting to note that none of the CD patients presented with gastrointestinal symptoms. All short children should be screened for CD irrespective of gastrointestinal symptoms.

Baixa estatura por haploinsuficiência do gene SHOX: do diagnóstico ao tratamento

Studies involving patients with short stature and partial deletion of sex chromosomes identified SHOX gene in the pseudoautosomal region of the X and Y chromosomes. SHOX haploinsufficiency is an important cause of short stature in a diversity of clinical conditions. It explains 2/3 of short stature observed in Turner syndrome (TS) patients. Heterozygous mutations in SHOX are observed in 77% of patients with Leri-Weill dyschondrosteosis, a common dominant inherited skeletal dysplasia and in 3% of children with idiopathic short stature, indicating that SHOX defects are the most frequent monogenetic cause of short stature. The sitting height/height ratio (SH/H) standard deviation score is a simple way to assess body proportions and together with a careful exam of other family members, effectively selected a group of patients that presented a high frequency of SHOX mutations. Growth hormone treatment of short stature due to TS is well established and considering the common etiology of short stature in patients with isolated defects of SHOX gene, this treatment is also proposed for these patients. Here, we review clinical, molecular and therapeutic aspects of SHOX haploinsufficiency.

The diagnostic work up of growth failure in secondary health care; An evaluation of consensus guidelines

BackgroundAs abnormal growth might be the first manifestation of undetected diseases, it is important to have accurate referral criteria and a proper diagnostic work-up. In the present paper we evaluate the diagnostic work-up in secondary health care according to existing consensus guidelines and study the frequency of underlying medical disorders.MethodsData on growth and additional diagnostic procedures were collected from medical records of new patients referred for short stature to the outpatient clinics of the general paediatric departments of two hospitals (Erasmus MC – Sophia Children's Hospital, Rotterdam and Spaarne Hospital, Haarlem) between January 1998 and December 2002. As the Dutch Consensus Guideline (DCG) is the only guideline addressing referral criteria as well as diagnostic work-up, the analyses were based on its seven auxological referral criteria to determine the characteristics of children who are incorrectly referred and the adequacy of workup of those who are referred.ResultsTwenty four percent of children older than 3 years were inappropriately referred (NCR). Of the correctly referred children 74–88% were short corrected for parental height, 40–61% had a height SDS <-2.5 and 21% showed height deflection (Δ HSDS < -0.25/yr or Δ HSDS < -1). In none of the children a complete detailed routine diagnostic work up was performed and in more than 30% no routine laboratory examination was done at all. Pathologic causes of short stature were found in 27 children (5%).ConclusionExisting guidelines for workup of children with suspected growth failure are poorly implemented. Although poorly implemented the DCG detects at least 5% pathologic causes of growth failure in children referred for short stature. New guidelines for referral are required with a better sensitivity and specificity, wherein distance to target height should get more attention. The general diagnostic work up for short stature should include testing for celiac disease in all children and for Turner syndrome in girls.

Sind kleinwüchsige Jungen als Erwachsene benachteiligt? - Nachuntersuchung von 77 Männern mit konstitutioneller Entwicklungsverzögerung und (oder) familiärem Kleinwuchs

Out of a total of 119 adult males seen in our clinic for short stature in childhood, but not treated (no organic cause for short stature and no endocrine failure), 77 (mean age 24.5 [20-30] years) were re-evaluated. At initial presentation (mean age 13.7 years) their heights were 2.4 (1.5-4.0) SDs below the mean height for age. The mean final height attained was 167.4 (158.3-181.2) cm, or -1.5 (-2.85 to +0.45) SDs from the population mean. Objective parameters (marital status, number of children, school leaving qualifications, career development) and subjective attitudes of the former patients to their height were assessed. The proportion of subjects who were married (15.6%) and the number of children (a total of 16) did not differ significantly from the population mean (18.1% married, expected number of children = 12. There was a trend towards higher educational achievement (23.4% vs. 19.5% "Abitur" [academic school leaving examination] or "Fachabitur" [technical school leaving examination]). Between 80 and 95% of the former patients reported that their height presented no handicap in daily life, in seeking a partner or in their careers. On the hypothetical question of treatment with a growth accelerator, enthusiasm was negatively correlated with height in childhood and the final height attained (Spearman rank correlation, P less than 0.01). The explanations concerning disordered growth given at the time were seen as useful by only about half of the former patients.

Precocious puberty in Turner syndrome

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.

An Etiologic Evaluation of Children with Short Stature in Gorgan (Northeast Iran), 2005

Growth is an important biological process during childhood. Short stature is the most common cause of a child to be examined by an endocrinologist. This cross-sectional study was performed to determine the short stature causes in children aged 6-14 years old in 2005 who were referred to Talghani Medical-Educational Center. Demographic characteristics, history of any serious problem (prematurity), clinical feature, biochemical and endocrinological test results and radiological findings were evaluated. Standard Deviation Score (SDS) was calculated and written down in an information recording form. From 100 children under study (66%) were girls with the average age of 10.84 year. Their average of bone age was 8.4 year. Most common causes for short stature were constitutional (57%), growth hormone deficiency (30%) and familial (8%). There was not significant difference between two sexes in this view. According to the findings, after ruling out of Constitutional and familial causes, we strongly recommended the provocative growth hormone test for early detection and timely prevention of permanent short stature.

Genetic disorders in the GH–IGF-I axis in mouse and man

Animal knockout experiments have offered the opportunity to study genes that play a role in growth and development. In the last few years, reports of patients with genetic defects in GH-IGF-I axis have greatly increased our knowledge of genetically determined causes of short stature. We will present the animal data and human reports of genetic disorders in the GH-IGF-I axis in order to describe the role of the GH-IGF-I axis in intrauterine and postnatal growth. In addition, the effects of the GH-IGF-I axis on the development and function of different organ systems such as brain, inner ear, eye, skeleton, glucose homeostasis, gonadal function, and immune system will be discussed. The number of patients with genetic defects in the GH-IGF-I axis is small, and a systematic diagnostic approach and selective genetic analysis in a patient with short stature are essential to identify more patients. Finally, the implications of a genetic defect in the GH-IGF-I axis for the patient and the therapeutic options will be discussed.

Squamous Cell Carcinoma of the Vulva in Turner Syndrome

Turner syndrome (gonadal dysgenesis) is an important cause of short stature in girls and primary amenorrhoea, which is usually caused by loss of part or all the X-chromosome. It is well known that women with Turner syndrome are liable to develop various diseases such as autoimmune diseases like thyroiditis, and cardiovascular, urologic and bone structural diseases in addition to hypertension and diabetes 1 However the risk of cancer, with the exception being in the case of colonic and rectal cancers, does not seem to be elevated in Turner syndrome 1. Carcinoma of the vulva is a rare gynaecological cancer and in Turner syndrome it is extremely rare. We report a case of squamous cell carcinoma (SCC) of the vulva in a 61 year old Caucasian woman diagnosed with Turner syndrome at the age of 15. Radical vulvectomy with en-block inguinal femoral lymphadenectomy was carried out. Histopathological examination of the specimen confirmed complete excision of the tumour with absence of metastasis to the lymph nodes. Conclusion: This seems to be the first reported case of SCC of the vulva in a patient with Turner syndrome.