Familial short stature caused by ACAN gene mutation:a familial case report / 临床儿科杂志

Objective To explore the clinical phenotype and genetic variation of familial short stature. Method The clinical data of a familial short stature pedigree in Guangxi Zhuang autonomous region were retrospectively analyzed. The disease-causing gene was identified using targeted high-throughput sequencing combined with Sanger sequencing in May 2017. The related literature were searched and the relationship between the clinical phenotype and genotype of the ACAN gene mutation were summarized. Results The two patients were brothers, one was 9-year and 10-month old boy and the other was 7-year-old boy. Both of them had short stature. Their parents were non-consanguineous marriage and both were 150 cm in height, with. Their uncle and grandpa are also short stature. Gene sequencing revealed a novel heterozygous variation c.6193delC (p.Gln2065Serfs*27) in exon 12 of ACAN gene in both brothers, which were inherited from their father. No report of this mutation was found by searching literature and databases. A total of 11 related articles in English were retrieved. Totally (including our study) 32 patients in 41 families were reported to have the pathogenic variants of ACAN gene, including 4 variants from Chinese children, but no such reports were found in Chinese literatures. The most common clinical manifestation is idiopathic short stature, which is mostly familial but could also be sporadic. Some children also suffered from osteoarthritis, disc herniation or degeneration. Most of the children had advanced bone age, but some of them were normal or even lagged. Treatment of postponing puberty by growth hormone combined with gonadotropin-releasing hormone analogues can effectively improve final height. Conclusion Heterozygous mutation of ACAN gene can cause short stature in children and has significant familial genetic characteristics, and the clinical characteristics have no relationship with genotypes.

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.

Etiology of short stature in Northern India / Journal of the ASEAN Federation of Endocrine Societies

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.

Controversias en el manejo de la talla baja idiopática

La talla baja idiopática (TBI) es un diagnóstico de exclusión que abarca un amplio y heterogéneo grupo de niños aparentemente sanos pero con talla inferior a -2 desviaciones estándar. En los Estados Unidos está aprobado el uso de hormona de crecimiento (HC) en niños con TBI, a diferencia de la mayoría de países Europeos. La respuesta terapéutica de los niños con TBI tratados con HC es muy variable y dependiente de múltiples factores al inicio y durante el tratamiento, por lo cual el beneficio de su uso no ha podido establecerse de forma consensual. Esta revisión recoge información actualizada sobre los más recientes estudios publicados en pacientes con TBI tratados con HC hasta alcanzar talla final, los diferentes factores asociados a la respuesta terapéutica, los efectos metabólicos, psicosociales y efectos adversos de la HC, y sobre otras opciones terapéuticas a considerar tales como HC con análogos de la GnRH, inhibidores de aromatasa e IGF1 humana recombinante.

Idiopathic short stature (ISS) is an exclusion diagnostic which includes a broad and heterogeneous group of supposedly healthy children with height below -2 standard deviations. In the United States, treatment with growth hormone (GH) is approved for children with ISS, as opposed to the majority of European countries. The final height of children with ISS whom are treated with GH is highly variable and dependent on multiples factors at the beginning and during the treatment. For this reason, the indication of GH therapy in ISS children is not consensual. This revision contains actual data about the most recently published studies in patients with ISS treated with GH until final height, associated factors to height gaining, metabolic, psychosocial and adverse events, and finally, other therapeutic options such as GH combined with GnRH analogues, aromatase inhibitors and recombinant human IGF1.

Uso de GH em pacientes com baixa estatura idiopática: [revisão] / GH treatment in patients with idiopathic short stature: [review]

Pacientes com baixa estatura idiopática podem ser tratados com GH. Os critérios clínicos e laboratoriais utilizados na decisão do uso do GH, bem como no reconhecimento da responsividade dos indivíduos ao tratamento, são discutidos. Não apenas os resultados antropométricos, mas também os aspectos éticos e psicossociais devem ser considerados na avaliação dos custos/benefícios envolvidos no tratamento com GH em pacientes com baixa estatura idiopática.

Growth hormone has been used in the treatment of patients with idiopathic short stature. Clinical and laboratorial criteria are discussed, taking into consideration the indication of GH and the evaluation of its efficacy and individual responsiveness. Anthropometric, psychosocial, ethical, and also cost/benefit aspects must be considered before GH prescription in idiopathic short stature patients.

Clinical Manifestation of Children with Failure to Thrive / 대한소아소화기영양학회지

PURPOSE: This study was to investigate the clinical manifestations of FTT in children. METHODS: From March 1997 to July 1999, clinical observations were made on patients with FTT who had visited to Samsung Medical Center. Detailed histories and through physical examinations were taken, and when suspected organic FTT, basic laboratory studies were done. RESULTS: Upon the review of medical records, we investigated the clinical manifestations of 74 children, aged 1 month and 13 year 1 month. The causes of FTT were composed of either physiologic (47.8%) or pathologic (52.2%) ones. Among the physiologic FTT, were there familial short stature (FSS, 14.5%), intrauterine growth retardation (IUGR, 14.5%), constitutional growth delay (CGD, 11.6%), idiosyncrasy and prematurity. Among pathologic causes, neurologic disorders (20%) are the most common causes of FTT, and then follow by GI (13.4%), allergic and infectious disorders in decreasing order. The data showed that average caloric intake in patients with FTT was 76.2% of recommended amount. FTT patients with CGD, IUGR, and idiosyncrasy had tendency to take small foods. The FTT children with prematurity, IUGR and pathologic FTT, were short and thin for their ages. However FTT children with CGD and FSS had tendency to be thin with relatively normal heights for their ages, in comparison with those of the children with prematurity, IUGR and pathologic FTT. CONCLUSION: The diagnosis of FTT was easily obtained with simple and through medical history, physical examination, and minimal laboratory tests. In this study, organic FTT was more prevalent than physiologic one. This results indicate that early intervention is mandatory, because children may develop significant long-term sequelae from nutritional deficiency.

Response of Growth Hormone Treatment to Final Height in Children with Growth Hormone Deficiency and Familial Short Stature / 대한소아내분비학회지

PURPOSE: A number of studies have been published on the effect of growth hormone therapy over 1-3 years in children with growth hormone deficiency(GHD) & Familial short stature(FSS). So far final height data are seldomly available. Final heights of GH treated children with GHD & FSS were evaluated. METHODS: 10 Children with GHD and 69 children with with FSS were enrolled for the study. They were treated with GH 0.1IU/kg/daily in 10 GHD and 20 children with FSS. They were grown up and reached adult height. 49 children with FSS were not treated at all. Facors influencing final height were investigated. RESULTS: 1) All patients with GHD(Idiopathic 8 cases, Organic 2 cases) had additional gonadotropin deficiency and had multiple pituitary hormone deficiency. 2) At start of GH treatment boys of idiopathic GHD were 9.8 years old and 12.4 years old in girls and their mean height was 114.8cm(-2.8SDS), 123.0cm(-2.9 SDS)in boys and girls respectively. Boy with orgnaic GHD was 11.1 years and 6.7 years old in girl. Their height were 126.0cm(-1.5SDS) and 104cm(-1.2SDS) respectively. 3) Mean final height of idiopathic GHD was 167.6cm(-0.5SDS) in male and 161.0 cm(0.7SDS) and that of organic GHD was 173.0cm(0.5SDS) in male and 157cm (0SDS) in girl. 4) Mean Final height in untreated children with FSS was 159.8+/-.2cm(-1.6 SDS)in male and 149.6+/-.3cm(-1.4SDS) in female. Mean final height of GH treated in FSS was 162.5+/-.1cm(-1.5SDS) in male and 152.0+/-.4cm(-1.2SDS) in female But there was no statiscally difference between untreated and treated children in final height. 5) The age of onset of menarche was 12.74+/-.78 years old in GH treated group (n=12) and 12.45+/-.16 years old in untreated group(n=34). CONCLUSION: The GH administration in patients with GHD has been confirmed for growth promotion. but in case of FSS there was no significant difference between treated and untreated group. More further studies are needed for the confirmation of the efficacy of GH therapy in patients with FSS.

Tibial Lengthening in Familial Short Stature ( Classic Ilizarov Method v . s . Combined Intramedullary Nailing ) / 대한정형외과학회잡지

Ilizarov technique has been successfully applied to limb lengthening for several decade, one of its main drawback is, however, long application of external fixator over 6 months. To lessen this time, simultaneous intramedullary fixation which convert later to static fixation by insertion of interlocking screws has been proposed. The indication for surgical limb lengthening includes familial short stature below the 3rd percentile. We compared the results of thirteen tibial lengthening with Ilizarov method to that of eleven hybrid methods. The hybrid system is composed of an unreamed AO intramedullary nail (IM) and ring fixator. Once the lengthening is completed, distal interlocking screws were inserted. In the group who were treated by hybrid system, the mean lengthening of tibia was 7.1cm (range, 6.3-9.5), the mean of external fixation period 7 months (range, 5-9), the mean healing index 1.2 month/cm (range, 1.1-1.4). On the other hand, the mean lengthening of tibia was 7.5cm (range, 5-10.3), the mean of external fixation period 9.8 months (range, 6-15), the mean healing index 1.4 month/cm (range, 1.1-1.8) in the group treated by Ilizarov method. Mean follow-up period was 23 months (range 14-47). There was no rotational or angular deformities and no loss of lengthening in the hybrid group. However we experienced three cases of angular deformity at the distraction site during lengthening in Ilizarov group. There was no deep infection in both groups. In the hybrid group we found several advantages such as no deformity, no loss of lengthening, and less scar by early removal of fixator, but some disadvantages such as need of subsequent procedures and limitation in intramedullary nailing.