Familial Short Stature Research Articles

Diagnostic Accuracy of Growth Rate in Differentiating Etiologies of Short Stature in Children

Background Short stature is a manifestation of a wide variety of conditions that some of which may be amenable to timely treatment and a suboptimal growth rate may be an early marker pointing to the cause of growth retardation. This study was conducted to evaluate the diagnostic utility of growth rate in differential diagnosis of children with short stature. Materials and Methods All children between the ages of 2 and 18 years who visited in pediatric endocrinology clinic in a five years period were recruited in a prospective cohort study. Children with standing height Results One hundred forty three patients fulfilled the inclusion criteria. Mean follow up period was 14.4±10.9 months. Etiologies of short stature were: constitutional growth delay (CGD) 46.9%, familial short stature (FSS) 28.7%, hypothyroidism 4.2%, growth hormone deficiency (GHD) 4.2% and miscellaneous causes in 16% of patients. Mean Z- score for children with constitutional growth delay was -2.3±0.69, in familial short stature was -2.3±0.65 and for other condition was -2.7±1.49. There was a meaningful statistical correlation between growth rate and etiology of short stature (P 0.05). Conclusion There was significant difference in growth rate between children with constitutional growth delay and familial short stature in comparing to short stature due to endocrine problem and other etiologies. Assessment of growth rate has some utility in diagnosing the etiology of short stature.

Etiology of Short Stature in Northern India

Objective. Short stature can be caused by a great variety of congenital and acquired conditions, some of which present with additional symptoms and signs. Overall, the number of patients seeking medical attention for short stature may be considered as the tip of the iceberg. The objective of this study was to determine the pattern and etiological factors of short stature in children. Methodology. A cross-sectional study was carried out in the Department of Endocrinology at a tertiary care health center in north India from August 2012 to June 2015. Four hundred and fifty one children (280 boys and 171 girls), ranging from 4 to 18 years presenting with short stature were studied. Anthropometric measurements were plotted on Indian standard growth charts. Results. In this study, the male to female ratio was found to be 1.6:1, with mean chronological age of 11.6+3.2 years, and mean bone age of 7.8+2.8 years. The common etiologic factors in the order of frequency were constitutional delay in growth and puberty (41.2%), familial short stature (15.9%), type 1 diabetes mellitus (9.9%), and hypothyroidism (8.6%) while growth hormone deficiency (2.4%) was a relatively uncommon cause. The most common pathological cause for proportionate short stature was type 1 diabetes and for disproportionate short stature was hypothyroidism. Hypothyroidism caused the maximum retardation of bone age while the least bone age retardation was noticed in familial short stature. Conclusion. Physiological/normal variants outnumbered the pathological causes of short stature. Endocrinological causes were found in almost one fourth of children with short stature; however, growth hormone deficiency was found in only 2.4% of the children.

Etiology of Short Stature in First Five Years of Life

Dear Editor, Short stature (SS) is one of the common causes of referrals to pediatric endocrinologists. The most common causes of SS included familial SS and constitutional growth delay, but a wide spectrum of the diseases can result to SS. It is evident that the correct understanding of the etiology of short stature in any society can be a good guide for diagnostic and therapeutic policies. So, many endocrine centers attempted to study the etiology of SS in their areas. This is a descriptive study and conducted in Kashan University of Medical Sciences. Any child under 5 years with a height less than the 3rd percentile of standard growth curves has been enrolled. Data including age, gender, family history of short stature, history of chronic diseases such as bowel disease, malnutrition, celiac disease and drug history from the parents or the child were obtained. The height and weight of the children and parents were measured. The physical examination was performed to find the cause of short stature. Preliminary tests were performed for all children including CBC, thyroid function tests, electrolytes, urinalysis and creatinine. Other tests based on the suspected disorders. A left wrist and hand X-ray was performed for all cases to determine bone age and evidences of bone dysplasia. A total of 67 children were included, the mean age was 2.5 ± 1.45 years (39 male and 28 female). Average height was 77.36 ± 14.6 cm and mean weight was 9.26 ± 3.4 kg. Overall the most common cause was short stature in a background of low birth weight (LBW) (23.9%) followed by constitutional growth delay (14.9%), familial short stature (11.9%) and growth hormone deficiency (10.5%). Most common causes of short stature in different age groups included: 0 2 years: Short stature in a background of low birth weight was the most common (n = 12, 44.4%) followed by the metabolic disorders and syndromes each of the 4 patients (14.8%). 2-5 years: Familial short stature (20.5 %), different syndromes (20.5 %) and constitutional short stature (17.9%). Metabolic disorders: Cystinosis, phenylketoneuria and organic academia. Syndromes: Down syndrome (most common), Noonan syndrome, Turner syndrome and unknown syndromes. Other causes: Nephrogenic diabetes insipidus, pycnodysostosis, chronic hepatitis, achondroplasia and hypochondroplasia. One case of hypochondroplasia also had hypothyroidism. One patient with achondroplasia had also growth hormone deficiency. Growth hormone deficiency is a quietly treatable cause of short stature in children and had a relatively high prevalence in our study (10.5%). Growth hormone deficiency has been reported in other studies with a prevalence of 34.3% in Majcher et al. study, 15% in Chowdhury et al. study and 30% in Mohammadian et al. study [1-3]. An interest finding in our study was the association of two important cause of short stature in some cases such as hypothyroidism in a girl with achondroplasia and growth hormone deficiency in another girl. The prevalence of chromosomal abnormalities in our work was relatively high (9%) and Down syndrome was the most common disorder. A prevalence of 20% of chromosomal abnormalities in short stature children also has been reported [2].

Syndromes with short stature

At present, factors that have been recognized as being able to influence growth are: nutritional, physical, chemical, psychological and genetic. The causes of short stature are numerous, with about 90% of cases classified as Idiopathic Short Stature and divided into 2 types familial short stature and constitutional short stature. Part of the population with growth disorders are SGA newborns (10%) who don't show recovery growth that physiologically should occur within 2-3 years in 90% of cases. Generally in this group there are both children small due to severe prematurity and children afflicted by genetic syndromes. Syndromes are the subject of our interest and we thought it would be useful to distinguish different prenatal and postnatal patterns of growth. In fact, some specific patterns can characterize syndromes. For example, very slow prenatal and postnatal growth is typical of Silver-Russell Syndrome; low prenatal and childhood growth followed by obesity after 3 years of life is typical of Prader–Willi syndrome; prenatal and postnatal overgrowth is typical of Beckwith–Wiedemann syndrome; and prenatal overgrowth followed by low postnatal growth is typical of Costello syndrome. Short stature can be harmonious or disharmonious; harmonious ones include familiar short stature, constitutional growth delays, GH deficiency, intrauterine growth restriction, dysmorphic or genetic syndrome and short stature in the presence of chronic diseases. In this paper we discuss the growth patterns of some genetic syndromes, such as achondroplasia, CHARGE syndrome, Cornelia de Lange syndrome, 22q11.2 deletion syndrome, Downs syndrome, Fetal – alcohol syndrome, Kabuki syndrome, Noonan syndrome, Prader-Willi syndrome, Rubistein–Taybi syndrome, Silver–Russell syndrome, Turner syndrome, Williams syndrome and VACTERL/VATER association.

Update on Common Childhood Endocrine Disorders

This issue focuses on a number of common childhood endocrine disorders. Dr. Stacy Meyer and her contributing colleagues have done an excellent job putting together a very readable overview of those disorders. The article begins with a topic that is “front and center” on most parents minds when they see their child’s primary clinician: is my child growing normally? Following the formula for estimating genetic linear growth potential (for both boys and girls) and tips on an appropriate physician examination when there are concerns about linear growth, Dr. Meyer reviews the differential diagnosis and treatment of children with short stature—including familial short stature and growth hormone deficiency. This practical approach for primary care clinicians continues throughout the article. Growth is followed by an overview of normal pubertal development, another common parental concern (for teens too!) in primary care. The management of precocious puberty (central and peripheral) and delayed puberty are addressed in this section. Dr. Meyer then reviews conditions that produce euthyroid states in which the efficacy of treatment is controversial—e.g., TSH elevation in obese children. Of course, there are numerous hypothyroid and hyperthyroid diseases of childhood that respond to therapy and Dr. Meyers carefully reviews important aspects of the management of these childhood diseases, including childhood thyroid cancer. As Dr. Meyer and her colleagues note in their conclusion, pediatric endocrinology is evolving with new effective treatment options for children with endocrine disorders. Because the presentation of pediatric endocrine disease can be quite variable the primary care clinician must have an index of suspicion to identify children who will benefit from therapy early in their disease. Within this issue Dr. Meyer and her contributing colleagues have given the primary care clinician the “gift” of a well organized, easily readable compendium of childhood endocrine disorders as well as an overview of normal growth and pubertal development. This issue is a valuable resource for all clinicians who provide primary health care to children and their families.

Failure to thrive in babies and toddlers.

Failure to thrive in a child is defined as 'lack of expected normal physical growth' or 'failure to gain weight'. Diagnosis requires repeated growth measurements over time using local, age-appropriate growth centile charts. Premature babies with appropriate growth velocity and children with 'catch-down' growth, constitutional growth delay or familial short stature show normal growth variants, and usually do not require further evaluation. In Singapore, the most common cause of failure to thrive in children is malnutrition secondary to psychosocial and caregiver factors. 'Picky eating' is common in the local setting and best managed with an authoritative feeding style from caregivers. Other causes are malabsorption and existing congenital or chronic medical conditions. Child neglect or abuse should always be ruled out. Iron deficiency is the most common complication. The family doctor plays a pivotal role in early detection, timely treatment, appropriate referrals and close monitoring of 'catch-up' growth in these children.

CO-84 – Retard statural en milieu scolaire: prévalence et étiologies

Statural growth is underpinned by development of the growth plate during the process of endochondral ossification, which is strongly regulated by numerous local factors (intracellular, paracrine and extracellular matrix factors) and systemic factors (nutrition, hormones, proinflammatory cytokines and extracellular fluids). This explains why growth retardation can be associated with numerous pathologies, particularly genetic syndromes, hormonal or inflammatory conditions, or gastrointestinal disorders having a nutritional impact. However, in most cases (80%), no specific aetiology is found after clinical investigation and conventional additional tests have been carried out. In such cases, “idiopathic” short stature is diagnosed, which includes patients presenting with constitutional delay of growth and development and familial short stature, but also patients with very subtle constitutional skeletal dysplasia which are not easily identifiable. In recent years, new methods of genetic investigation (e.g. gene panels, exome or genome sequencing) have made it possible to identify many genetic variants associated with apparently isolated short stature. Indeed, it is still difficult to estimate the proportion of patients presenting with idiopathic short stature for which a molecular diagnosis of monogenic conditions could be made. This estimate varies hugely depending on the thoroughness of the clinical, laboratory and radiological assessments performed prior to molecular analysis, since retrospective analysis of positive cases usually reveals subtle signs of underlying syndromes or rare skeletal disorders. Molecular diagnosis in children is important to be able to offer genetic counselling and to organise patient management. Moreover, improved understanding of the molecular basis of these cases of short stature opens up numerous possibilities for more specific treatments targeting the growth plate.© 2022 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Assessment of bone turnover markers and bone mineral density in normal short boys.

To investigate whether there is a change in bone turnover-related biochemical markers and bone mineral density of children with constitutional delay of growth and puberty (CDGP) in the prepubertal period. We measured serum calcium, phosphorus, alkaline phosphatase, parathormone, 25-OH vitamin D, osteocalcin, osteoprotogerin and urinary deoxypyridinoline levels (D-pyd), and bone mineral density (BMD) in 31 prepubertal boys with CDGP. These children were compared with 22 prepubertal boys with familial short stature (FSS) and 27 normal prepubertal boys. Urinary D-pyd was significantly high in CDGP group as compared to control group (p=0.010). Volumetric BMD did not significantly differ between CDGP, FSS, and control groups (p=0.450). Volumetric BMD and urinary D-pyd levels of FSS and control groups were similar. Mean or median levels of calcium, phosphorus, alkaline phosphatase, parathormone, and osteoprotegerin did not significantly differ between CDGP, FSS, and control groups. Our data suggest that prepubertal boys with CDPG have normal bone turnover. However, their significantly higher urinary D-pyd levels relative to those of FSS and control groups might be an indicator of later development of osteoporosis. Therefore, long-term follow-up studies monitoring bone mineral status of prepubertal boys with CDPG from prepuberty to adulthood are needed to better understand bone metabolism of these patients.

Etiologies and characteristics of children with chief complaint of short stature.

PurposeShort stature is a very common reason for visits to pediatric endocrine clinics. It could be the first sign of an underlying disease. The purpose of this study is to investigate the etiologies and general characteristics of subjects who visited an outpatient clinic due to short stature.MethodsWe retrospectively reviewed the medical records of 3,371 patients who visited Severance Children's Hospital with the chief complaint of short stature from 2010 to 2012. Medical history, auxological data, and laboratory tests including bone age were collected and analyzed. Chromosome studies or combined pituitary function tests were performed if needed.ResultsApproximately 89.4% of the subjects with the chief complaint of short stature who visited the outpatient clinic were of normal height, and only 10.6% of subjects were identified as having short stature. Of the subject of short stature, 44.7% were classified as having normal variant short stature; that is, familial short stature (23.0%), constitutional delay in growth (17.7%), and mixed form (3.9%). Pathological short stature was found in 193 subjects (54.2%). Among pathological short stature, most common etiology was growth hormone deficiency (GHD) (38.9%).ConclusionA majority of children had a normal height. Among children with short stature, pathological short stature and normal variants occupied a similar percentage. GHD was the most common cause of pathological short stature and found in about 20% of the children with short stature. In pathological short stature, the height, height velocity, and IGF-1 level were lower than in normal variants.

Baixa Estatura e haploinsuficiência do gene SHOX

Introduction: SHOX gene (short stature homeobox gene) deficiency is one of the most frequent genetic causes of isolated or familial short stature, with highly variable clinical severity.Case-report: The authors describe a 14 year-old-girl, with short limbs and short stature. The wrist X-ray showed Madelung deformity. The molecular study showed deletion of the SHOX gene (FISH del (X) (Xp22.3Xp22.3) (SHOX). A very careful physical examination, including measurement of body proportions, is of extreme importance in the clinical evaluation of short stature. The Madelung deformity can only appear in the adolescence. Treatment with growth hormone can improve the final height.Discussion/Conclusions: The prevalence of short stature due to SHOX gene mutations among children with short stature appears to be similar to that of Growth Hormone deficiency or Turner syndrome. The authors’ intention is to draw attention to this clinical entity, since a timely diagnosis can have therapeutic implications.

Measuring agreement between cervical vertebrae and hand-wrist maturation in determining skeletal age: Reassessing the theory in patients with short stature

The objective of this study was to determine the degree of agreement between hand-wrist radiography and cervical vertebral maturation analysis in patients diagnosed with short stature. A cross-sectional study was designed; 178 patients (90 girls, 88 boys) diagnosed with short stature and seeking treatment were selected. The patients were divided into 2 groups (76 with familial short stature, 102 with nonfamilial short stature). Hand-wrist and lateral cephalometric radiographs were obtained from the patients. The hand-wrist radiographs were analyzed using the Fishman method, and the lateral cephalometric views were categorized according to the method of Hassel and Farman. The degree of agreement between the 2 methods of predicting skeletal maturation was measured by calculating the contingency coefficient and the weighted kappa statistic. A high degree of agreement was observed between the 2 methods of analyzing skeletal maturation. It was also observed that agreement was higher in girls in the familial short-stature group, whereas boys had higher agreement in the nonfamilial short-stature group. Cervical vertebral maturation can be a valuable substitute for hand-wrist radiography in patients with short stature.

Growth hormone significantly increases the adult height of children with idiopathic short stature: comparison of subgroups and benefit.

BackgroundChildren with Idiopathic Short Stature do not attain a normal adult height. The improvement of adult height with treatment with recombinant human growth hormone (rhGH), at doses of 0.16 to 0.28 mg/kg/week is modest, usually less that 4 cm, and they remain short as adults. The benefit obtained seems dose dependent and benefits of 7.0 to 8.0 cm have been reported with higher doses of 0.32 to 0.4 mg/kg/week, but the number of studies is limited. The topic has remained controversial.ObjectiveThe objective was to conduct a retrospective analysis of our experience with 123 children with ISS treated with 0.32 ± 0.03 mg/kg/week of rhGH, with the aim of comparing the different subgroups of non-familial short stature, familial short stature, normal puberty, and delayed puberty and to assess the benefit by comparison with 305 untreated historical controls, from nine different randomized and nonrandomized controlled studies.ResultsEighty eight of our children (68 males and 20 females) attained an adult height or near adult height of -0.71 SDS (0.74 SD) (95% CI, -0.87 to -0.55) with a benefit over untreated controls of 9.5 cm (7.4 to 11.6 cm) for males and 8.6 cm (6.7 to 10.5 cm) for females.In the analysis of the subgroups, the adult height and adult height gain of children with non-familial short stature were significantly higher than of familial short stature. No difference was found in the cohorts with normal or delayed puberty in any of the subgroups, except between the non-familial short stature and familial short stature puberty cohorts. This has implications for the interpretation of the benefit of treatment in studies where the number of children with familial short stature in the controls or treated subjects is not known.The treatment was safe. There were no significant adverse events. The IGF-1 values were essentially within the levels expected for the stages of puberty.ConclusionOur experience was quite positive with normalization of the heights and growth of the children during childhood and the attainment of normal adult heights, the main two aims of treatment.

Bone Marrow Aspirate Concentrate and Platelet-rich Plasma Enhanced Bone Healing in Distraction Osteogenesis of the Tibia

During lower limb lengthening, poor bone regeneration is a devastating complication. Several local or systemic applications have been used to promote osteogenesis, and biologic stimulations are gaining attention, but their utility has not been proven in this setting. In patients undergoing bilateral tibial lengthening, we compared those receiving an osteotomy site injection of autologous bone marrow aspirate concentrate (BMAC) plus platelet-rich plasma (PRP) with those not receiving such an injection in terms of external fixator index (time in external fixation divided by amount of lengthening), full weightbearing index (time until a patient was permitted to do full weightbearing divided by amount of lengthening), four cortical healing indexes (time until each cortical union divided by amount of lengthening), and callus shape and type. Twenty-two patients (44 tibias) undergoing bilateral tibial lengthening enrolled in this randomized trial. Two patients were excluded, one due to insufficient radiographic evaluation and one who was lost to followup, leaving 20 patients (40 segments) for inclusion. Ten patients (20 segments) received BMAC combined with PRP injection (treatment group) and 10 patients (20 segments) received no injection (control group). All patients underwent stature lengthening for familial short stature with the lengthening over nail technique. Autologous BMAC combined with PRP was injected at the tibial osteotomy site at the end of the index surgery. Mean distraction rates were similar between groups (0.75 mm/day in the treatment group versus 0.72 mm/day in the control group; p = 0.24). Full weightbearing was permitted when we observed radiographic evidence of healing at two cortices; this assessment was made by the surgeon who was blinded to the treatment each patient received. Minimum followup was 24 months (mean, 28 months; range, 24-34 months). There was no difference in mean external fixator index between groups. However, mean cortical healing indexes (anterior/posterior/medial/lateral) were 1.14/0.81/0.96/0.88 months/cm in the treatment group and 1.47/1.26/1.42/1.22 months/cm in the control group (all p < 0.001), showing faster healing in the treatment group at each cortex. Full weightbearing was permitted earlier in the treatment group than in the control group (index: 0.99 months/cm and 1.38 months/cm, respectively, p < 0.001). Callus shape and type were not different between groups. Autologous BMAC combined with PRP injection at the osteotomy site helped improve bone healing in distraction osteogenesis of the tibia, although the effect size was small. Level I, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Quality of referral of short children to the paediatric endocrinologist and impact of a fax communication system

In 2001, a chart review of children referred to the authors' endocrine clinic because of short stature revealed that many were referred with insufficient baseline data, had normal height velocity and were within genetic target height. Therefore, a two-way fax communication system was implemented between referring physicians and the authors' service before the first visit. Aspects that were assessed included whether this system increased the information accompanying the patient at referral, resulted in children with nonpathological shortness not being seen in the clinic, and was used differently by paediatricians and general practitioners. Between January and December 2006, 138 referrals for short stature, diagnosed with familial short stature, constitutional delay or idiopathic short stature, were audited (69 with and 69 without previous fax communication). Data collected included source of referral, clinical information provided, available growth measurements, and results from laboratory and imaging studies. Fax communication resulted in growth curves being provided more often (95.6% of cases versus 40.5% of cases without fax communication [P<0.001]) and more investigations being performed by the referring physician (median [range]: six [zero to 13] investigations versus one [zero to 11]; P<0.001), as well as a diagnosis of nonpathological short stature being given to 31 children based on the growth curve, laboratory and imaging results, without the children being seen in the endocrine clinic. Fax communication was also used more frequently by paediatricians (84%) than by general practitioners (15%). The fax communication system resulted in a more complete evaluation of referred patients by their physicians and reduced the number of unnecessary visits to the authors' specialty clinic while promoting medical education.

Clinical and Nutritional Assessment of Short Statured Indian Children with Celiac Disease

Introduction: Celiac disease is an autoimmune disease, which is increasingly recognized as a cause of short stature in genetically susceptible population. The present study was undertaken to look for prevalence of celiac disease among the pediatric population with short stature (SS) and to study characteristics of these short statured children with celiac disease. Materials and Methods: This is a prospective study conducted at a tertiary teaching hospital at Bikaner, Rajasthan to look for the occurrence of celiac disease amongst the pediatric population (&lt;15 years) with short stature (n=100). Other common causes of short stature were also identified. Results: Out of 100 short statured children, 38 (38%) had celiac disease and other major causes responsible were hypothyroidism, pituitary disorders, constitutional growth delay, and familial short stature. Chronic diarrhea, anorexia, anemia and behavioral changes were statistically more common in short statured children (&lt;15 years) having celiac disease than non celiac patients. Conclusion: We conclude that celiac disease is not an uncommon cause of short stature and stunted growth in this region. All short statured patients should be screened for celiac disease. DOI: http://dx.doi.org/10.3126/jnps.v33i2.7912 J Nepal Paediatr Soc. 2013; 33(2):91-94

Heterozygous Mutations in Natriuretic Peptide Receptor-B (NPR2) Gene as a Cause of Short Stature in Patients Initially Classified as Idiopathic Short Stature

Based on the stature observed in relatives of patients with acromesomelic dysplasia, type Maroteaux, homozygous for mutations in natriuretic peptide receptor B gene (NPR2), it has been suggested that heterozygous mutations in this gene could be responsible for the growth impairment observed in some children with idiopathic short stature (ISS). The objective of the study was to investigate the presence of NPR2 mutations in a group of patients with ISS. The NPR2 coding region was directly sequenced in 47 independent patients with ISS. The functional consequences of NPR2 nonsynonymous variations were established using in vitro cell-based assays. Three novel heterozygous NPR2 mutations were identified: c.226T>C (p.Ser76Pro), c.788G>C (p.Arg263Pro), and c.2455C>T (p.Arg819Cys). These allelic variants were not found in our controls or in the 1000 Genomes database. In silico analysis suggested that the three missense mutations are probably damaging. All of them were selected for in vitro functional evaluation. Cells transfected with the three mutants failed to produce cyclic GMP after treatment with C-type natriuretic peptide. Cells cotransfected with mutant and wild-type-NPR-B (1:1) showed a significant decrease in cGMP levels after C-type natriuretic peptide stimulation in comparison with cells cotrasnfected with empty vector and wild type, suggesting a dominant-negative effect. These three mutations segregated with short stature phenotype in an autosomal dominant pattern (height SD score ranged from -4.5 to -1.7). One of these patients and two relatives have disproportionate short stature, whereas in another patient a nonspecific skeletal abnormality was observed. All three of these patients were treated with recombinant human GH (33-50 μg/kg · d) without significant height SD score change during therapy. We identified heterozygous NPR2 mutations in 6% of patients initially classified as ISS. Affected patients have mild and variable degrees of short stature without a distinct phenotype. Heterozygous mutations in NPR2 could be an important cause of nonsyndromic familial short stature.

Familial short stature is associated with a novel dominant‐negative heterozygous insulin‐like growth factor 1 receptor (IGF1R) mutation

Familial short stature is associated with a novel dominant‐negative heterozygous insulin‐like growth factor 1 receptor (<scp>IGF</scp>1<scp>R</scp>) mutation

Clinical expression of familial Williams-Beuren syndrome in a Turkish family

Williams-Beuren syndrome (WBS) is a rare genetic disorder characterized by distinctive facial features, intellectual disability with a typical neurobehavioral profile, cardiovascular anomalies, and occasional infantile hypercalcemia. Majority of cases occur sporadically, and only a few cases of familial WBS have been reported. Although pre- and post-natal growth retardation is a common clinical feature of the syndrome, growth hormone deficiency is detected only in a few patients. To our knowledge, there has only been one report about familial Williams-Beuren syndrome in the Turkish population. Here, we report on the three molecular cytogenetically confirmed familial Williams-Beuren syndromes detected in a family with familial short stature. The father, daughter, and son analyzed with clinical and laboratory findings, and reasons of the short stature in Williams-Beuren syndrome are discussed through the literature.

Low Incidence of Pathology Detection and High Cost of Screening in the Evaluation of Asymptomatic Short Children

To determine the incidence of pathology during routine screening of healthy short children, testing adherence to a consensus statement on the diagnosis and treatment of children with idiopathic short stature, and the cost per identified diagnosis resulting from comprehensive screening. Retrospective chart review of 1373 consecutive short stature referrals evaluated at the Cincinnati Children's Hospital Medical Center Pediatric Endocrinology Clinic between 2008 and 2011. We identified 235 patients with a height of <3rd percentile, negative history and review of systems, and normal physical examination. Outcome measures were incidence of pathology detection, diagnostic group characteristics, clinicians' adherence to testing guidelines, and screening costs. ANOVA and χ(2) were used to analyze the data. Nearly 99% of patients were diagnosed as possible variants of normal growth: 23% with familial short stature, 41% with constitutional delay of growth and maturation, and 36% with idiopathic short stature. The incidence of newly diagnosed pathology was 1.3%: 1 patient with biopsy-proved celiac disease, 1 with unconfirmed celiac disease, and 1 with potential insulin-like growth factor I receptor defect. On average, each patient had 64.3% of the recommended tests for age and sex; 2.1% of patients had all of the recommended testing. The total screening tests costs were $315321, yielding $105107 per new diagnosis entertained. Healthy short children do not warrant nondirected, comprehensive screening. Future guidelines for evaluating short stature should include patient-specific testing.

Profile and Height Outcomes of Children with Short Stature in North India: An Experience from a Tertiary Care Centre

To the Editor: The ongoing dynamicity in the populationin terms of change in nutritional status, improved edu-cation, awareness and access to health care is expectedto bring changes in the etiologies causing short stature(SS). This study aimed to evaluate the current etiolog-ical trends for SS and the effect of treatment on finalheight. Retrospective analysis of records of childrenreferred for SS from2003–2007withatleast4yearsfollowup was done in the Department of Endocrinology,Vardhman Mahavir Medical College & Safdarjung Hos-pital, New Delhi. (Fig. 1). SS was defined as height<3rd percentile and/or height velocity <5th percentilefor chronological age.Records of 139 children [68 girls; 71 boys; age of pre-sentation: 11.34±3.71 y (Range 2–21 y)] were analyzed ofwhich74(53.24%)hadreached18yage.Thisstudyhighlights the predominantly late presentation of childrenwith SS in India. Familial short stature (FSS)(36, 26 %) wasthe most common cause of SS followed by hypothyroidism(26, 19 %), growth hormone deficiency (GHD) (19, 14 %),constitutional delay in growth and puberty (CDGP) (17,12 %), genetic syndromes [Turner’s(n=7); Down’ssyndrome (n=4)] (11, 8 %), Celiac disease (8, 6 %),nutritional (8, 6 %), achondroplasia/hypochondroplasia(6, 4 %), chronic disease (2, 1 %) and idiopathic(6,4 %). FSS and CDGP together constitute normalvariant SS (NVSS) and is the most common cause ofSS in our country, constituting 9 % [3], 16 % [4]and20 % [5] of all SS children in different studies and38 % in our study. This increased proportion of childrenwith NVSS in our series may reflect the increasedawareness in the society and increased healthcare seek-ing. Being a referral centre our patient profile is likelyto be skewed and it is likely that NVSS is even morecommon in the population.There was a significant difference in the presenting heightstandard deviation score (SDS) (P=0.002), final height SDS(P<0.001) and the change in height SDS (Δ Ht SDS)(P<0.001) depending on the etiology of SS (Table 1). Maxi-mum height improvement (ΔHt SDS) was seen in treatedGHD children followed by treated hypothyroid andCDGP. Poor height outcomeofchildrenwithCeliacdiseaseinourstudymaybetheresultofdelayeddiagnosisandlackofcompliance to gluten free diet. Poor height outcomes in chil-drenwithachondroplasia/hypochondroplasia and SS due tosyndromes reflect the limited growth potential in thesechildren. Endocrine disorders should be actively lookedfor, since they comprise of a third of children with SS andshowmaximumimprovementinheightontreatment.Thoughthere has been increased healthcare seeking,it is quite late asevident from our study. Increased awareness among generalpopulation and pediatricians would help early detection oftreatable cases and better height of the population.