Short Stature Patients Research Articles

Comparison of the clinical picture and hormonal test results in children with growth hormone deficiency and idiopathic short stature – diagnostic difficulties and brief overview

Introduction and objective: Short stature is a common paediatric problem. Some children with short stature present growth hormone (GH) deficiency (GHD), whereas others have no hormonal disturbances (idiopathic short stature, ISS). Distinguishing between these two conditions is the task of the paediatric endocrinology centres. The aim of this study was to compare the clinical picture and hormonal tests results in patients with short stature caused by GHD and ISS. Materials and methods: The study included 100 short stature children. In all the children, medical history was obtained and a physical examination was performed. Next, bone age, insulin-like growth factor type 1 (IGF-1) levels, and GH secretion in two stimulation tests were assessed. With respect to the GH results, the children were divided into two groups: GHD (n = 38) and ISS (n = 62). Results: There were no significant differences between the groups with respect to age, sex, puberty stage, bone age, birth length and birth weight. Growth retardation was observed in both groups with a similar frequency, but in the ISS group it occurred significantly earlier. The mother’s height was lower in the ISS group. Body mass was significantly higher, but IGF-1 significantly lower in the GHD group. In both groups, the maximum GH secretion in the stimulation tests was higher after clonidine than after glucagon, which indicates that this test is more reliable. Conclusions: A similar degree of growth deficiency, growth rate deceleration and bone age delay are observed in ISS and GHD children, though ISS children are thinner and have higher IGF-1 levels. Despite some differences in clinical presentation, all short stature patients with growth rate deceleration should undergo thorough diagnostic testing along with GH stimulation tests.

Simulation of Changes in Tensile Strain by Airbag Impact on Eyes After Trabeculectomy by Using Finite Element Analysis.

We studied the kinetic phenomenon of an airbag impact on eyes after trabeculectomy using finite element analysis (FEA), a computerized method for predicting how an object reacts to real-world physical effects and showing whether an object will break, to sequentially determine the responses at various airbag deployment velocities. A human eye model was used in the simulations using the FEA program PAM-GENERISTM (Nihon ESI, Tokyo, Japan). A half-thickness incised scleral flap was created on the limbus and the strength of its adhesion to the outer sclera was set at 30%, 50%, and 100%. The airbag was set to hit the surface of the post-trabeculectomy eye at various velocities in two directions: perpendicular to the corneal center or perpendicular to the scleral flap (30° gaze-down position), at initial velocities of 20, 30, 40, 50, and 60 m/s. When the airbag impacted at 20 m/s or 30 m/s, the strain on the cornea and sclera did not reach the mechanical threshold and globe rupture was not observed. Scleral flap lacerations were observed at 40 m/s or more in any eye position, and scleral rupture extending posteriorly from the scleral flap edge and rupture of the scleral flap resulting from extension of the corneal laceration through limbal damage were observed. Even in the case of 100% scleral flap adhesion strength, scleral flap rupture occurred at 50 m/s impact velocity in the 30° gaze-down position, whereas in eyes with 30% or 50% scleral flap adhesion strength, scleral rupture was observed at an impact velocity of 40 m/s or more in both eye positions. An airbag impact of ≥40 m/s might induce scleral flap rupture, indicating that current airbags may induce globe rupture in the eyes after trabeculectomy. The considerable damage caused by an airbag on the eyes of short-stature patients with glaucoma who have undergone trabeculectomy might indicate the necessity of ocular protection to avoid permanent eye damage.

A study on genotypes and phenotypes of short stature caused by epigenetic modification gene variants.

Mendelian disorders of the epigenetic machinery (MDEMs) are caused by genetic mutations, a considerable fraction of which are associated with epigenetic modification. These MDEMs exhibit phenotypic overlap broadly characterized by multiorgan abnormalities. The variant detected in genes associated with epigenetic modification can lead to short stature accompanied with multiple system abnormalities. This study is aimed at presenting and summarizing the diagnostic rate, clinical, and genetic profile of MDEMs-associated short stature. Two hundred and fourteen short-stature patients with multiorgan abnormalities were enrolled. Clinical information and whole exome sequence (WES) were analyzed for these patients. WES identified 33 pathogenic/likely pathogenic variants in 19 epigenetic modulation genes (KMT2A, KMT2D, KDM6A, SETD5, KDM5C, HUWE1, UBE2A, NIPBL, SMC1A, RAD21, CREBBP, CUL4B, BPTF, ANKRD11, CHD7, SRCAP, CTCF, MECP2, UBE3A) in 33 patients (15.4%). Of note, 19 variants had never been reported previously. Furthermore, these 33 variants were associated with 16 different disorders with overlapping clinical features characterized by development delay/intelligence disability (31/33; 93.9%), small hands (14/33; 42.4%), clinodactyly of the 5th finger (14/33; 42.4%), long eyelashes (13/33; 39.4%), and hearing impairment (9/33; 27.3%). Additionally, several associated phenotypes are reported for the first time: clubbing with KMT2A variant, webbed neck with SETD5 variant, retinal detachment with CREBBP variant, sparse lateral eyebrow with HUWE1 variant, and long palpebral fissure with eversion of the lateral third of the low eyelid with SRCAP variant.Conclusions: Our study provided a new conceptual framework for further understanding short stature. Specific clinical findings may indicate that a short-stature patient may have an epigenetic modified gene variant.

Efficacy and safety of GH treatment in Japanese children with short stature due to SHOX deficiency: a randomized phase 3 study.

We conducted a randomized phase 3 study to investigate the efficacy and safety of GH treatment in prepubertal Japanese patients with short stature due to SHOX deficiency. The patients were randomly allocated to the GH-GH group (n = 10), in which the patients were treated with GH (0.35 mg/kg/wk) subcutaneously once daily for 24 mo, or the no-treatment (NT)-GH group (n = 9), in which the patients were untreated for the first 12 mo and then administered the same dosage of GH for the next 12 mo. At month 12, the ∆height standard deviation score (SDS) for chronological age (CA) and serum IGF-1 level were significantly higher in the GH-GH group than those in the NT-GH group. In contrast, bone age (BA) and ΔBA/ΔCA were numerically higher in the GH-GH group but were not statistically significant. At month 24, these parameters were comparable between the two groups. The height velocity was significantly larger in the GH-GH group during the first year and in the NT-GH group during the second year. No serious adverse drug reactions were observed; however, one patient in the GH-GH group exhibited increased insulin resistance at month 24. These results indicated that GH is a promising treatment option for short stature in patients with SHOX deficiency.

Salt-Wasting Congenital Adrenal Hyperplasia in A 2-Year-Old Patient

Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder due to deficiencies of enzymes involved in steroidogenesis in the adrenal cortex. It is known that 90% of CAH are due to 21-hydroxylase enzyme deficiency caused by mutation of the CYP21A2 gene. A female patient aged two years and one month old was reported with a diagnosis of salt-wasting CAH. The diagnosis was based on complaints of genital enlargement since birth. The patient had developed repeated vomiting and severe dehydration since newborn. The patient was diagnosed with CAH and under treatment with glucocorticoid replacement therapy by a pediatrician since the age of 5 months. Body height/age < -3 Standard Deviation (SD) of the Z-score chart (very short stature) and ambiguous genitalia were reported. Laboratory tests indicated thrombocytosis (795x103/uL), mild hyperkalemia (5.4 mmol/L), and increased testosterone (110.1 ng/dL). Bone age study affirmed an advanced bone age. History of increased 17-hydroxyprogesterone (109.19 ng/mL) and decreased morning serum cortisol levels (1.7 ug/dL). History of gynecological ultrasonography (USG) showed uterus, no bilateral testicular structure, hyperplasia of the left adrenal gland, and suggestive of genital ambiguity. The 21-hydroxylase deficiency causes a decrease in aldosterone and cortisol and an increase in androgens. Hypoaldosteronism causes hypovolemia, hyponatremia and hyperkalemia. Hypocortisolime causes hypoglycemia, decreased response to infection, and stress. Hyperandrogenism causes virilization of the genitalia and short stature in patients. A female patient aged two years and one month old was reported with a salt-wasting congenital adrenal hyperplasia diagnosis. Chromosome analysis was the recommended test in this case.

Short stature is a risk factor for heart transplant morbidity and mortality.

Short stature is associated with mortality after cardiac surgery and may increase size mismatch risk among transplant recipients. Yet, stature's impact on heart transplant outcomes is not well-characterized. The Scientific Registry of Transplant Recipients was queried for data on all adult heart transplants in the United States from 2000 to 2022. Recipients were stratified into five cohorts by sex-corrected stature. Morbidity was assessed with Kruskal-Wallis and chi-squared tests. Mortality was analyzed using Kaplan-Meier estimation. Risk factors for mortality were assessed with multivariable Cox regression. Among 43,420 transplant recipients, 5321 (12.2%) had short stature (females >4'11″ & ≤5'1″; males >5'4″ & ≤5'7″) and 765 (1.8%) had very short stature (females ≤4'11″; males ≤5'4″). Very short stature patients had higher waitlist status (1A and 1), more congenital heart disease, and received more oversized donor hearts than other cohorts (all p < 0.05). Very short stature patients had decreased 30-day, 1-, 5-, and 10-year survival (94.6%, 84.3%, 69.3% and 52.5%, respectively, all p < 0.001), but less acute rejection (p = 0.005) and comparable stroke rates (p = 0.107). On multivariable regression adjusting for congenital heart disease and oversized donor hearts, very short and short stature were associated with 10-year mortality (hazard ratios: 1.40 and 1.12, respectively, both p < 0.005). Short stature confers increased mortality risk for heart transplant recipients and merits inclusion in prognostic models.

EZ blocker failure in short-stature patient: Is the gap sufficient? - A case study.

EZ blocker failure in short-stature patient: Is the gap sufficient? - A case study.

Novel pathogenic NPR2 variants in short stature patients and the therapeutic response to rhGH

ObjectiveHeterozygous loss-of-function variants in the NPR2 gene cause short stature with nonspecific skeletal abnormalities and account for about 2 ~ 6% of idiopathic short stature. This study aimed to analyze and identify pathogenic variants in the NPR2 gene and explore the therapeutic response to recombinant growth hormone (rhGH).MethodsNPR2 was sequenced in three Chinese Han patients with short stature via exome sequencing. In vitro functional experiments, homology modeling and molecular docking analysis of variants were performed to examine putative protein changes and the pathogenicity of the variants.ResultThree patients received rhGH therapy for two years, and two NPR2 heterozygous variants were identified in three unrelated cases: c.1579 C > T,p.Leu527Phe in patient 1 and c.2842dupC,p.His948Profs*5 in patient 2. Subsequently, a small gene model was constructed, and transcriptional analysis of the synonymous variant (c.2643G > A) was performed in patient 3, which revealed the deletion of exon 17 and the premature formation of a stop codon (p.His840Gln*). Functional studies showed that both NPR2 variants, His948Profs*5 and His840Gln*, failed to produce cGMP in the homozygous state. Furthermore, the Leu527Phe variant of NPR2 was almost unresponsive to the stimulatory effect of ATP on CNP-dependent guanylyl cyclase activity. This loss of response to ATP has not been previously reported. The average age of patients at the start of treatment was 6.5 ± 1.8 years old, and their height increased by 1.59 ± 0.1 standard deviation score after 2 years of treatment.ConclusionIn this report, two novel variants in NPR2 gene were described. Our findings broaden the genotypic spectrum of NPR2 variants in individuals with short stature and provid insights into the efficacy of rhGH in these patients.

Obstetric and perinatal outcome in short-stature patients.

Scarce data exist regarding obstetric complications of short-stature patients. This study aimed to investigate obstetric and perinatal outcomes in women with short stature; specifically, to investigate whether short-stature patients are at an increased risk for cesarean delivery. A population-based cohort study was conducted, including all singletons born between the years 1991 and 2021 at a tertiary medical center. Obstetric and perinatal outcomes of short-stature patients were compared with those of non-short patients. A generalized estimation equation binary logistic model was constructed to adjust for confounders and maternal recurrence in the cohort. The study population included 356 356 parturient; among them, 14 035 (3.9%) were short-stature patients. Short-stature patients had significantly higher rates of cesarean delivery (20.7% vs 13.7%, odds ratio = 1.64, 95% confidence interval 1.57-1.71, P < 0.001), induction of labor, pathologic presentations, prolonged second stage of labor, non-reassuring fetal monitoring, and meconium-stained amniotic fluid. Newborns of short-stature patients had a significantly higher risk of being small for gestational age as compared with those of non-short patients. In the generalized estimation equation models, the association between short stature and risk of cesarean delivery remained significant (adjusted odds ratio = 1.32, 95% confidence interval 1.27-1.38, P < 0.001), as well as the risk of small for gestational age newborns (adjusted odds ratio = 1.51, 95% confidence interval 1.40-1.63, P < 0.001), but not for the other adverse outcomes. Maternal short stature is an independent risk factor for cesarean delivery and is associated with small for gestational age newborns.

Quality of life in children and adolescents with growth hormone deficiency and their caregivers: an Italian survey

PurposeThe aim of this study was to produce evidence on quality of life (QoL) among Italian growth hormone deficiency (GHD) children and adolescents treated with growth hormone (GH) and their parents.MethodsA survey was conducted among Italian children and adolescents aged 4–18 with a confirmed diagnosis of GHD and treated with GH therapy and their parents. The European Quality of Life 5 Dimensions 3 Level Version (EQ-5D-3L) and the Quality of Life in Short Stature Youth (QoLISSY) questionnaires were administered between May and October 2021 through the Computer-Assisted Personal Interview (CAPI) method. Results were compared with national and international reference values.ResultsThe survey included 142 GHD children/adolescents and their parents. The mean EQ-5D-3L score was 0.95 [standard deviation (SD) 0.09], while the mean visual analogue scale (VAS) score was 86.2 (SD 14.2); the scores are similar to those of a reference Italian population aged 18–24 of healthy subjects. As for the QoLISSY child-version, compared to the international reference values for GHD/ idiopathic short stature (ISS) patients, we found a significantly higher score for the physical domain, and lower scores for coping and treatment; compared to the specific reference values for GHD patients, our mean scores were significantly lower for all domains except the physical one. As for the parents, we found a significantly higher score for the physical domain, and a lower score for treatment; compared to reference values GHD-specific, we found lower score in the social, emotional, treatment, parental effects, and total score domains.ConclusionsOur results suggest that the generic health-related quality of life (HRQoL) in treated GHD patients is high, comparable to that of healthy people. The QoL elicited by a disease specific questionnaire is also good, and comparable with that of international reference values of GHD/ISS patients.

Downregulation of ACAN is Associated with the Growth hormone pathway and Induces short stature.

ACAN heterozygous mutations can cause short stature in patients with or without advanced bone age and have recently attracted researchers' attention. Growth hormone can be used to treat short stature induced by ACAN mutations; however, few studies have focused on the underlying mechanism of this treatment. Four patients with new mutations were reported based on clinical data and genetic tests. We investigated the expression and Gene Ontology biological process enrichment of ACAN and GH pathways based on GTEx databases through bioinformatics analyses. The effect of ACAN on the growth hormone response evaluated in ATDC5 cells with a growth hormone stimulation test. Four mutations were reported in this study: c.619C > A, c.1967A > G, c.1888G > A, and c.1308_1309del. All patients' heights were under -2.5 SD, with one had advanced bone age, and two had GH deficiency. Two individuals received growth hormone therapy acquired variable levels of height SD score improvement. ACAN and the GH pathway were strongly associated; ACAN does not affect GHR but regulates the response to GH. Downregulating ACAN inhibited ATDC5 cell proliferation induced by GH. ACAN is associated with the GH pathway, revealing the potential mechanism underlying GH-targeted treatment for ACAN mutation-induced short stature. GH-promoting therapies may increase patients' heights.

An Observational Study on Response to Growth Hormone Therapy in Indian Patients of Short Stature with Special Emphasis on Biochemical Parameters and Bone Biomarkers.

There is a lack of Indian data on short stature treatment using recombinant human growth hormone (rhGH). We explored the effects of such treatment in eastern Indian patients, with emphasis on biochemical parameters and bone biomarkers in addition to basic anthropometry. Our descriptive study covered 50 short stature patients of varied aetiology attending endocrine outpatient department (OPD) of a tertiary care teaching hospital. Patients were followed up for 1 year after the index visit, and prospective data were reconciled with past medical records. A dose of rhGH used was 0.18-0.375 mg/kg as standard, starting dose mostly being 0.2 mg/kg. Dosing was adjusted if the physician judged the clinical outcome to be less favourable than expected. Anthropometric parameters (height, weight, body mass index (BMI) and skeletal age) were recorded clinically, and various biochemical parameters and bone biomarkers were estimated from blood. Among 50 subjects, 60% had idiopathic growth hormone (GH) deficiency and 26% had Turner's syndrome. The median age at treatment start was 10 years, and the median treatment duration was 25.5 months. The height increased more in the first year of therapy. In the last 6 months, the height velocity was approximately 0.5 cm/month. Although the weight increased significantly, the increment slowed down in the last 6 months. Both remained less than age- and gender-matched references throughout. The skeletal age was on average 2 years behind chronological age (CA)-being 8.7, 9.6 and 11.3 years, respectively, at therapy start, after one year and at study end. Fasting blood glucose (FBG), total cholesterol and calcium level changes were not statistically significant. Serum cortisol and phosphate showed a modest but statistically significant rise, while thyroid-stimulating hormone (TSH) level declined. Insulin-like growth factor 1 (IGF-1) increase was relatively pronounced. Among bone biomarkers, a decrease in CTx and an increase in vitamin D were significant. Dual-energy X-ray absorptiometry (DEXA) data indicated that bone mineral density was less than that of age-matched controls despite treatment. The therapy was well tolerated. rhGH treatment leads to significant improvement in anthropometry in Indian children comparable with Western data. Bone biomarker changes indicate decreased bone resorption and increased bone formation although bone mineral density still lags behind age-matched controls.

Robot-assisted laparoscopic repair in hiatal hernia with kyphosis: A case report with meta-analysis

Abstract BACKGROUND: Hiatal hernia is a high incidence disease, of which, partial patients requiring surgery have gastroesophageal reflux or dysphagia. Although minimally invasive surgery has been widely utilized in recent years, the optimal surgical therapy still remains controversial. In this study, we reported a kyphosis patient undergoing robot-assisted laparoscopic hiatal hernia repair and launched a meta-analysis aiming to evaluate the advantages of this surgery strategy. MATERIALS AND METHODS: Six databases (Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, EMBASE, ClincialTrials.gov database and Web of Science) were searched from inception to September 20, 2022. All studies describing the patients undergoing robotic hiatal hernia or laparoscopic hiatal hernia were included. And the meta-analysis was performed using R package meta (v6.0.0). RESULTS: We reported a 75-year-old female patient of short stature and with severe kyphosis was diagnosed with hiatal hernia and underwent a robotic surgery. For meta-analysis, 1,128 articles were identified in the initial database search, and among them, 6 articles were included in the final analysis. The results showed that robotic surgery had no advantage in operation time and intraoperative complications rate compared with traditional laparoscopic surgery (both P &lt; 0.01). Regardless of the statistical significance, robotic surgery tended to have a lower conversion and postoperative complication rate, as well as the length of hospital stay. CONCLUSIONS: Robotics have some advantages in the surgical treatment of hiatal hernia compared with the conventional laparoscopic surgery, the use of which can facilitate the treatment for some challenging cases.

Wrist radiography for hand bone age tells a lot; a girl with SHOX deficiency

Madelung's deformity (MD) occurs as a result of premature closure of the medial and volar aspects of the distal radial physis.1 It is more frequent and severe in girls, and usually develops in middle/late childhood.2 MD is one of the most characteristic features of he short-stature homeobox gene (SHOX) deficiency, which causes short stature3. Radial bowing is one of the well-known radiological futures. On the other hand, there are three typical radiological sign of the hand radiograph for SHOX deficiency; triangularization, pyramidalization of the os lunatum, and radiolucency at the distal radius4.&#x0D; In the evaluation of a 9-year-old girl who was investigated for precocious puberty, her height measurement was 18th percentile. On the wrist X-ray taken for the determination of the bone age of the patient, there was an appearance compatible with MD (Figure 1). In the genetic studies of the patient with MD, normal female karyotyping (46, XX) was demonstrated by Trypsin G banding Technique. Heterozygous SHOX deletion was detected by Fluorescence In Situ Hybridization technique using a probe specific to the SHOX gene region (Xp22.33).&#x0D; Interpreting the direct X-ray is important in recognizing the MD. Thus, it will be easier to detect SHOX gene deletion in the etiology of short stature patients with this deformity.

PSAT107 Evaluating Pituitary Volume and the Growth Hormone Stimulation Test in Siblings. Both Together Better Define the Etiology of Short Stature.

Abstract We have shown that short children have significantly reduced pituitary volume (PV)s and have speculated PV as a cause for diminished chronic growth hormone (GH) secretion and poor growth. In this study, we further elucidate the role of PV in the etiology of short stature (SS) in a larger cohort of siblings (SBs).The database of a Peds Endo Center between 2013-21 was queried for siblings with SS who underwent a GH Stimulation test (GHST) and MRI evaluation. Their results were compared with normal controls (NCs) as previously reported. 129 SBs of 60 families were compared to 170 NCs. SBs were divided into 3 groups (GPs). GP1 (n=79) consisted of families with only GHD. GP2 (n=12) contained families with only ISS SBs. GP3 (n=38) comprised families with mixed GHD and ISS. SBs &amp;lt;11 yrs and &amp;gt;11 yrs were considered prepubertal (prePB) and pubertal (PB), RSP. The mean (MN) and median (MD) age for both prePB and PB SBs were significantly different (p 0.05). The 32 PB patients in GP3 had a mean PV of 316.17± 197.53 mm3, which was significantly different from that of the PB NCs of 424.6 ± 138.4 mm3 (p&amp;lt;0.001). Out of 38 children in GP3, 18 passed the GHST and 11 of those children who passed demonstrated a small pituitary gland (61%). 78% of prePB SBs had small PVs, while 88% were GHD. 66% of PB SBs had small PVs, while 70% of PB SBs were GHD. 71% of all SBs had small PVs, while 77% were GHD. When combined, GHST and PV identify the etiology for SS in 92% of subjects. The GHST and PV together identify more patients of SS who should qualify and benefit from GH therapy than the GHST alone. Since ages were significantly different and present as a limitation to this study, future studies should strive for age match control Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Association of Spastic Paraplegia and Short Stature in Patients of Autosomal Recessive Intellectual Disability

Background: Intellectual Disability “ID” is a genetic disorder, which lead to arrested or incomplete development of the brain. It is the limitation of cognitive skills impairment and decline ability of a person in learning process. ID is the most common health problem in worldwide. These patients have decline intellectual functions and at least limitation in their two or more adoptive skills such as reading, writing abilities, social interactions, Behavioral habits, self-care, communication ability etc. The time period for the diagnosis of ID is the onset of disease before the eighteen years of age. Spastic Paraplegia and short stature is a general terminology using for a group of an uncommon inherited diseases that cause stiffness and weakness in the lower limbs muscles. Gradually its symptoms get worse with the passing of time. It's also called as familial spastic paraparesis or Strümpell-Lorrain syndrome. SP is classified clinically as “complicated" (syndromic) or "uncomplicated" (nonsyndromic) Spastic Paraplegia. Methods: This study was started in March 2014 to Aug 2015. The criteria for the selection of families were consanguineous families with two or more than two ID patients. The patients were examined, interviewed one by one in friendly atmosphere. Then the blood samples were taken by aseptic method. Blood samples were processed in laboratory. DNA extraction and PCR was done. After that Exome sequencing was used to find the pathogenic variants. The data was analyzed by CATCH. Sanger Sequencing was applied to see the segregation. Results: In ID-family1 the variant of AP4B1 was segregated with the disease phenotype. These ID patients have short stature and Spastic Paraplegia. Mutation in AP4B1 is known to cause intellectual disability. In ID-family2 the variants of WDR62, EML2 and KCNK6 were co-segregated with disease phenotype. But only mutations in WDR62 are known to cause intellectual disability. ID family2 also identified as short stature. In ID-family3 Exome sequencing data reveal no putative variants. Conclusion: The present study was conducted in three consanguineous families for the determination of the responsible genes for intellectual disability. Exome sequencing revealed putative mutations in AP4B1 and WDR62 in two out of three families. In third family we could not locate any putative mutation. Keywords: Intellectual disability ID, Autosomal recessive disorders, Autosomal recessive nonsyndromic ID, Behavioral Abnormality, Segregation, Exome sequencing, Spastic Paraplegia, Short stature.

Genetic characterization of short stature patients with overlapping features of growth hormone insensitivity syndromes

Genetic characterization of short stature patients with overlapping features of growth hormone insensitivity syndromes

Anaesthesia Management for Acquired Internal Hernia A Rare Cause of Subacute Intestinal Obstruction

Internal hernia are a rare cause of subacute intestinal obstruction in adults. Internal hernia has reported autopsy incidence of 0.2 – 0.9 % and is cause of small bowel obstruction in 0.6 – 5.8 % of cases. In this case report we present successful anaesthetic management of a 39-year-old Indian male with internal hernia presenting as subacute intestinal obstruction who underwent exploratory laparotomy under combined spinal epidural anaesthesia. This case provides that combined spinal epidural can be an effective technique for gastrointestinal surgery with spontaneous respiration in short stature patients. Keywords: Internal hernia, Sub­acute intestinal obstruction, Combined spinal epidural anaesthesia

Clinical impact of variants in non-coding regions of SHOX - Current knowledge.

The short stature homeobox-containing (SHOX) is the most frequently analysed gene in patients classified as short stature patients (ISS) or diagnosed with Leri-Weill dyschondrosteosis (LWD), Langer mesomelic dysplasia (LMD), or Madelung deformity (MD). However, clinical testing of this gene focuses primarily on single nucleotide variants (SNV) in its coding sequences and copy number variants (CNV) overlapping SHOX gene. This review summarizes the clinical impact of variants in noncoding regions of SHOX. RECENT FINDINGS: CNV extending exclusively into the regulatory elements (i.e., not interrupting the coding sequence) are found more frequently in downstream regulatory elements of SHOX. Further, duplications are more frequent than deletions. Interestingly, downstream duplications are more common than deletions in patients with ISS or LWD but no such differences exist for upstream CNV. Moreover, the presence of specific CNVs in the patient population suggests the involvement of additional unknown factors. Some of its intronic variants, notably NM_000451.3(SHOX):c.-9delG and c.-65C>A in the 5'UTR, have unclear clinical roles. However, these intronic SNV may increase the probability that other CNV will arise de novo in the SHOX gene based on homologous recombination or incorrect splicing of mRNA. SUMMARY: This review highlights the clinical impact of noncoding changes in the SHOX gene and the need to apply new technologies and genotype-phenotype correlation in their analysis.

Very Short Stature Predicts Morbidity and Mortality After Heart Transplant

<h3>Purpose</h3> Short stature has been linked to increased transplant waitlist times and operative mortality after heart surgery. We aim to describe the relationship between stature and heart transplant outcomes. <h3>Methods</h3> The United Network for Organ Sharing was queried for data on adult heart transplant recipients from 2000 to 2021. Recipients were stratified into five groups by height: very short stature (height ≥2 standard deviations [SD] below the mean), short stature (≥1 and <2 SD below the mean, average stature (within 1 SD of the mean), tall stature (≥1 and <2 SD above the mean), and very tall stature (≥2 SD above the mean). Morbidity was analyzed using Kruskal-Wallis and chi square tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests, and Cox regression. <h3>Results</h3> 2,033 (4.3%) heart transplant recipients from 2000 to 2021 had very short stature, 8,551 (18.0%) had short stature, 5,783 (12.2%) had tall stature and 667 (1.4%) had very tall stature. The very short stature group was younger, more commonly female, weighed less, had higher rates of congenital heart disease and restrictive cardiomyopathy, lower rates of pre-transplant mechanical ventilation, and lower serum creatinine than other groups (p<0.05). The very short stature group had increased 30-day mortality (8.1%, p<0.001), rejection rate (31.4%, p<0.001), postoperative stroke rate (3.9%, p=0.015), and median length of stay (16 days, p<0.001). Five-year survival rates ranged from 72.8% to 79.4% with the lowest in very short stature patients (p<0.001; Figure 1). On Cox regression, very short stature and short stature were associated with five-year mortality (HR 1.4, p<0.001 and HR=1.2, p<0.001 respectively), but donor/recipient height mismatch, weight mismatch, and predicted heart mass mismatch were not (HR 1.1, p=0.194; HR=1.0, p=0.709; and HR 1.0, p=0.772 respectively). <h3>Conclusion</h3> Very short stature is associated with increased morbidity and mortality after heart transplant. The mechanism explaining this effect requires further study.