kbg syndrome and growth hormone

The level of insulin-like growth factor 1 (IGF-1) was 42.0 ng/mL. This is probably due to a rapidly progressive pubertal development. Conclusion: Short stature is prevalent in KBG syndrome, and spontaneous catch-up growth beyond childhood appears limited. Although ANKRD11 appears to be a major gene associated with intellectual disability, KBG syndrome remains under-diagnosed. A 'new' malformation/retardation syndrome is described in 7 patients from 3 unrelated families. 11, Background: The mean (±SD) age and height SDS at treatment initiation were 12.4 (±3.0) years and -4.0 (±1.1) respectively, while median (IQR) serum insulin-like growth factor 1 (IGF-1) and peak growth hormone level on clonidine stimulation were 73 (25-167) ng/ml and 1.1 (0.4-3.6) ng/ml respectively. The roles of growth hormone include influencing our height, and helping build our bones and muscles. 2013;161A:835–840. Over the subsequent years, there was further graded fall in height velocity, declining to 4.8 ± 3.6 cm/year (n = 2) during the seventh year. Growth hormone (GH) or somatotropin, also known as human growth hormones (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. Our findings suggest that mutation of ANKRD11 is a common Mendelian cause of developmental delay. 8600 Rockville Pike Using the patients' initials, the condition has been designated the KBG syndrome. © 2008-2021 ResearchGate GmbH. KBG syndrome, due to ANKRD11 alteration is characterized by developmental delay, short stature, dysmorphic facial features, and skeletal anomalies. ANKRD11 expression was shown to be downregulated in breast cancer cell lines. Data on the therapeutic effects of growth hormone (GH) on children with KBG syndrome accompanied by short stature in the previous literature has not been summarized. Genomic microarray identified an intragenic 154 kb deletion at 16q24.3 within ANKRD11. We report the case of an Indian school-aged boy with dysmorphic features, intellectual disability and a clinical history characterized by seizures and hearing problems. Exogenous ANKRD11 expression enhanced the levels of acetylated p53 in both MCF-7 and MDA-MB-468 cells. It is characterized by macrodontia of the upper central incisors, distinctive facial dysmorphism, short stature, vertebral abnormalities, hand anomaly including clinodactyly, and various degrees of developmental delay. Am J Med Genet A. Case summary: Congenital heart defects, velopharyngeal insufficiency and hip anomalies were less frequent. Our findings support the role of ANKRD11 as a tumour suppressor gene and suggest that aberrant DNA methylation of three CpGs in a 19bp region within the ANKRD11 promoter may be responsible for its down-regulation in breast cancer. ANKRD11 is known to interact with nuclear receptor complexes to modify transcriptional activation. In 2011, heterozygous mutations in the ANKRD11 gene were identified in patients with KBG syndrome. Patient 5 showed no response to GH therapy without specific data of height velocity were not included in the figure. Broad knowledge of the clinical phenotype is essential for a correct interpretation of the molecular results. ... Endocrinologist – Short stature is somewhat common in KBG patients and families have opted for growth hormone therapies. The syndrome is pan-ethnic. Clin J Evid Based Pediatr. On the basis of our observations, we recommend cardiac assessment in children and regular hearing tests in all individuals with a molecular diagnosis of KBG syndrome. Growth hormone deficiency (GHD) is more likely to affect children rather than adults and is a symptom of several genetic diseases such as Prader-Willi syndrome and Turner Syndrome. The height velocity was highest during the first year of treatment (10.6 ± 3.0 cm/year), declining to 8.7 ± 2.7 and 7.9 ± 2.2 cm/year during second and third year, respectively. Soliman AT, Ramadan MA, Sherif A, Aziz Bedair ES, Rizk MM. Stature below the 3rd centile or -1.88 standard deviation score (SDS) was observed in 72% of KBG children and in 57% of KBG adults. There were ten children with KBG syndrome accompanied by short stature who received GH therapy in reported cases. Three patients required growth hormone treatment with a significant increase of height velocity. Here, we report two KBG patients who have different novel heterozygous mutations of ANKRD11 gene with wide range of clinical manifestations. She received GH therapy. ANKRD11 was shown to associate with the p53 acetyltransferases and cofactors, P/CAF and hADA3. All patients showed behavioral abnormalities and most had developmental delay. Kim SJ, Yang A, Park JS, Kwon DG, Lee JS, Kwon YS, Lee JE. Affected patients may not show the characteristic KBG phenotype and the diagnosis is therefore easily missed. Recently mutations in ANKRD11 have been documented in patients with KBG syndrome, and it has been proposed that haploinsufficiency of ANKRD11 is the cause of this syndrome. GH treatment is effective in our girl and most children with KBG syndrome accompanied by short stature during the first year of therapy. Materials and methods: Physical examination revealed mild dysmorphic features. Bethesda, MD 20894, Copyright The girl was referred to our department because of short stature. Height below -2.50 SDS was observed in 62% of KBG children and in 36% of KBG adults. Conclusions: Restoration of ANKRD11 expression in MCF-7 (wild-type p53) and MDA-MB-468 (p53(R273H) mutant) cells suppressed their proliferative and clonogenic properties through enhancement of CDKN1A (p21(waf1)/CIP1) expression. The former also received a gonadotropin-releasing hormone agonist due to medical necessity. North India. 2017 Dec;103:109-112. doi: 10.1016/j.ijporl.2017.10.017. This family has additional features that might expand the phenotype of KBG syndrome. There were no adverse reactions reported after GH treatment. The mean SDS of height in KBG children was -2.56 and in KBG adults -2.17. Human growth hormone (GH) is a substance that controls your body’s growth. A case of KBG syndrome caused by mutation of ANKRD11 gene and literature review. doi: 10.12998/wjcc.v8.i6.1172. 10.3969/j.issn.1673-5501.2018.06.011], Further delineation of the KBG syndrome phenotype caused by ANKRD11 aberrations, Ockeloen CW, Willemsen MH, de Munnik S, van Bon BW, de Leeuw N, Verrips A, Kant SG, Jones EA, -. KBG syndrome is an autosomal dominant disorder caused by pathogenic variants within ANKRD11 or deletions of 16q24.3 which include ANKRD11. Pycnodysostosis: clinical, radiologic, and endocrine evaluation and linear growth after growth hormone therapy. KBG syndrome is compatible with autonomous life in adulthood. ... At birth, auxological parameters are usually normal, as in our patient, and only later SS becomes evident. Through whole-exome sequencing, we identified deleterious heterozygous mutations in ANKRD11 encoding ankyrin repeat domain 11, also known as ankyrin repeat-containing cofactor 1. 1998 Jun;48(6):719-24. doi: 10.1046/j.1365-2265.1998.00407.x. We recognized a new feature of a wide anterior fontanelle with delayed closure in 22%. Patient 3 was followed by 9 mo, Patient 13 was followed by 8 mo, and three patients (P4, P9, and P10) did not show specific follow-up time. Most cases are identified in children. Am J Med Genet A. Aim: The relevant anthropometric, biochemical and radiological data at baseline and follow-up were recorded. See this image and copyright information in PMC. To date, KBG syndrome has been reported in 45 patients. Reynaert N, Ockeloen CW, Sävendahl L, Beckers D, Devriendt K, Kleefstra T, Carels CE, Grigelioniene G, Nordgren A, Francois I, de Zegher F, Casteels K. Horm Res Paediatr. KBG syndrome is a rare genetic disease characterized mainly by skeletal abnormalities, distinctive facial features, and intellectual disability. A splice-site mutation, c.7570-1G>C (p.Glu2524_Lys2525del), cosegregated with the disease in a family with three affected members, whereas in a simplex case a de novo truncating mutation, c.2305delT (p.Ser769GlnfsX8), was detected. Case presentation: Height SDS was improved in nine (9/10) of them. Epub 2017 Oct 12. In addition, ANKRD11 itself was found to be a novel p53 target gene. The constructs carrying -661 to -571bp promoter sequence showed significant transcriptional activity. Genetic analysis showed a c.2635 dupG (p.Glu879fs) mutation in the ANKRD11 gene. The exact cause of KBG syndrome is unknown, but most cases are believed to be autosomal dominant traits with variable degree of penetrance. Macrodontia of permanent upper central incisors was seen in 85%. Li QY, Yang L, Wu J, Lu W, Zhang MY, Luo FH. Brunner HG, van Loon RL, Smeets EE, van Haelst MM, van Haaften G, Nordgren A, Malmgren H, Approximately 60 patients have been reported since it was first described in 1975. Detailed orofacial phenotyping, including orthodontic evaluation, intra-oral photographs and orthopantomograms, was performed in 10 patients and revealed besides the hallmark feature of macrodontia of central upper incisors, several additional dental anomalies as oligodontia, talon cusps and macrodontia of other teeth. Mattei D, Cavarzere P, Gaudino R, Antoniazzi F, Piacentini G. Ital J Pediatr. KBG syndrome does not come with a set diagram of issues, or a clear-cut ... 4 KBG Foundation 2017 Growth is never by mere chance; it is the result of forces working together. Citation: Kim SJ, Yang A, Park JS, Kwon DG, Lee J-S, Kwon YS and Lee JE (2020) Two Novel Mutations of ANKRD11 Gene and Wide Clinical Spectrum in KBG Syndrome: Case Reports and Literature Review. ANKRD11 gene; Case report; Children; Growth hormone therapy; KBG syndrome; Short stature. De Boer H, Blok GJ, Voerman HJ, De Vries PM, van der Veen EA. Although it is uncommon, growth hormone deficiency may also be diagnosed in adults. Changes of height SDS of children with KBG syndrome accompanied by short stature in the reported literature and in our study. 2020 Nov 11;11:579805. doi: 10.3389/fgene.2020.579805. ANKRD11 gene and literature review. ANKRD11 enhanced the DNA-binding properties of mutant p53(R273H) to the CDKN1A promoter, suggesting that ANKRD11 can mediate the restoration of normal p53 function in some cancer-related p53 mutations. FOIA 2011;89:289–294. It is caused by an autosomal dominant mutant gene. 2001 Aug;50(8):905-11. doi: 10.1053/meta.2001.24924. Distinctive findings in this series included malrotation of the abdominal viscera, bilateral inguinal herniae in two patients, basal ganglia calcification and the finding of osteopenia in three patients. There were nine children with KBG syndrome accompanied by short stature who received growth hormone (GH) therapy (P1-P4 and P6-10) (black circle). Changes of height and weight in our patient with KBG syndrome during 2 years of growth hormone therapy. Here we studied a girl with KBG syndrome and collected the data of children with KBG syndrome accompanied by short stature from previous studies before and after GH therapy. Brain malformations were identified in 8 patients. Changes in serum IGF-I and IGFBP-3 concentrations during the IGF-I generation test performed prospectively in children with short stature. KBG syndrome is a rare condition characterised by a typical facial dysmorphism, macrodontia of the upper central incisors, skeletal (mainly costovertebral) anomalies and developmental delay. A case of KBG syndrome caused by mutation of It is characterized by distinctive facial features, developmental delay, short stature, and skeletal anomalies. Your child would need to be off GHT for 6 months to a year before having the stimulation test to prove growth hormone deficiency. Case presentation The pituitary gland is a structure in our brain that produces different types of specialised hormones, including growth hormone (also referred to as human growth hormone or HGH). Common features included hand anomalies, cryptorchidism, and a large number of palate abnormalities. Most deletions remove the 5'end or the entire coding region but never extend toward 16q telomere suggesting that distal 16q deletion could be lethal. 2020; 8 :1172–1179. COVID-19 is an emerging, rapidly evolving situation. We present the largest cohort of KBG syndrome cases confirmed by ANKRD11 variants reported so far, consisting of 20 patients from 13 families. Large upper central incisors were the diagnostic finding in all three patients along with mental retardation, cryptorchidism, skeletal abnormalities, and short stature. These findings demonstrate a role for ANKRD11 as a p53 coactivator and suggest the involvement of ANKRD11 in a regulatory feedback loop with p53. It is characterized by distinctive facial features, developmental delay, short stature, and skeletal anomalies. Whole exome sequencing (WES) was performed, and the novel heterozygous mutation, c3310dup, p. (Glu110GlyfsTer5) in ANKRD11 was identified. Among them, 19 were diagnosed after the detection of a 16q24.3 deletion encompassing the ANKRD11 gene by array CGH. Conflict-of-interest statement: The authors declare that they have no conflicts of interest.