Size Disproportion Research Articles

Abstract 11778: Comparison of Prenatal Diagnosis Rates and Cardiac Morphometry in Fetal Coarctation by Ultimate Surgical Repair Type

Background: Fetal diagnosis of coarctation of aorta is challenging, with limited data examining prenatal detection rates in patients requiring simple vs. extensive arch reconstruction. This study aims to evaluate prenatal detection rate s and fetal cardiac morphometric differences in neonates requiring simple vs. complex coarctation repair. Methods: Pre- and postnatal records of neonates with isolated coarctation repair from the Society of Thoracic Surgeons database from Jan 2010 - Dec 2020 at our center were reviewed. Patients were classified as requiring discrete (Group 1) or extended arch repair (Group 2). Fetal echocardiograms were measured by a single observer blinded to repair type. Results: Of 228 neonates requiring repair, 67 (29%) had a prenatal diagnosis. The proportion with prenatal diagnosis was not different in group 1 (28%) vs. group 2 (32%) (χ2 = 0.45, p = 0.5). At the first fetal echo (median gestational age (GA) of 21.9 wks in group 1 vs 23.6 wks in group 2, p = 0.2), there were no differences between groups when comparing right ventricular (RV) and left ventricular (LV) dimensions, valvular dimensions, or aortic arch dimensions. At the final fetal echo (median GA of 33.7 wks in both groups, p = 0.6), there were statistical differences between group 1 and 2 in RV geometry with ratio of RV minor to major axis (0.72 vs 0.83, p = 0.03) and ratio of LV to RV minor axis (0.68 vs 0.59, p = 0.02), ascending aorta Z score (-2.6 vs -3.4, p = 0.03), distal arch Z score (-3.9 vs -4.6, p = 0.048), and ratio of isthmus to distal arch dimension (0.88 vs 1.02, p = 0.045) (Figure). Conclusion: The rate of prenatal diagnosis in fetuses requiring neonatal coarctation repair remains low, regardless of ultimate surgical repair type. Fetuses ultimately requiring extensive arch repair have smaller aortic sizes, and greater RV/LV size disproportion in the third trimester. This data may be useful in counseling families with regard to postnatal surgical management in fetuses with suspected coarctation.

The Alexis\xae system for laparoscopic splenectomy in pediatric patients

The laparoscopic splenectomy in pediatric patients is performed worldwide but often the disproportion between size of patients and size of organs requires an extra laparotomic access for spleen removal. The aim of the present study was to evaluate the safety and effectiveness of the Alexis® system to retrieve the spleen without additional laparotomic access. The charts of all patients who underwent splenectomy at our center during the last 5 years were retrieved. In all the cases the Alexis® system was placed in the umbilicus, thru which a 10 mm camera was inserted. Three additional 5 mm standard trocars were inserted. Seven patients, affected by spherocytosis (3), epidermoid cyst (2), idiopathic thrombocytopenic purpura (2) and thalassemia (1), underwent laparoscopic splenectomy at a median age of 10 years (range: 8–17). Median patients’ weight was 32.5 kg (range: 25–71) and spleen size 15 cm (11–18). In all the cases, upon removal of the camera, the retrieval bag was inserted thru the umbilicus under direct view, the spleen retrieved, morcellated, and removed. No conversion nor enlargement of one of the ports nor an extra laparotomic access were required. The patients were discharged on the fifth post-operative day and the cosmetic results were excellent. Removal of the spleen can be safely performed without any additional laparotomy thru the Alexis® system placed in the umbilicus. This system is effective also in case of major patient/organ size disproportion and the final cosmetic aspect is excellent.

Fragility and sensitivity analysis of steel frames with bolted-angle connections under progressive collapse

Robustness is a key factor in the safety of structures and structural components or sub-assemblies against progressive or disproportionate collapse, the latter term being classically used to indicate a significant disproportion in size between the initial and final damage configurations. Particularly for a steel moment-resisting frame (MRF), the connections play a pivotal role in the robustness and redundancy of the structural system because an alternative load path could be mobilised when/if the beam-column joints have enough capacity to sustain the abnormal extra-loads developed following the loss or notional removal of a support element as consequence of a triggering event.Although the latter is usually but not exclusively related to terrorist attacks (e.g. faulty construction, uncontrolled gas releases, etc.) and the structural behaviour inherently involves uncertainties in loads and system capacity, progressive collapse has been probabilistically assessed in a few studies, mainly focussed on reinforced concrete structures. In light of this, delving more into probabilistic approaches could be timely, and this paper presents the main results of sensitivity and fragility analysis of steel MRFs featuring top-and-seat with web angle connections, leading to the derivation of both tornado diagrams as well as fragility models. The former ones quantify the progressive collapse sensitivity to design parameters, whilst the latter ones provide the probability of failure as a function of a given intensity measure. Uncertainties in material and geometrical properties of building portfolios were modelled and propagated through Monte Carlo simulation, whereas component-based modelling was integrated with the pushdown methodology for damage analysis of the randomly sampled building realisations. The obtained results show the influence of the studied parameters/random variables on progressive collapse behaviour/fragility and provide insights into the effect of changing the seismic intensity for the design and the column-removal scenario for the assessment of a bolted-angle joint system that has not been probabilistically treated up until now.

P.236Myofibres with subsarcolemmal rims and/or central aggregates of mitochondria (SRCAM) are prevalent in congenital titinopathies

With increasing use of massive parallel sequencing over recent years, congenital titinopathies due to recessively inherited truncating and/or splice-site pathogenic variants in TTN (which encodes titin) are emerging as a common cause of congenital myopathy (CM). The clinical phenotype is broad. Muscle biopsies show structural abnormalities including cores, central nuclei (CN) and fibre size disproportion. We report a novel structural abnormality prevalent in muscle biopsies from a cohort of patients with clinical and/or pathological features (cores and/or central nuclei and slow fibre predominance) of CM. Cases were classified genetically as "definite" (2 predicted pathogenic TTN variants), "probable" (1 predicted pathogenic and 1 missense variant) and ''possible'' (1 predicted pathogenic or 2 missense variants) titinopathy. The index case, a male with recessive splice-site TTN variants in trans, presented at birth, with profound hypotonia, respiratory weakness and cardiomegaly. CK was normal. EMG was myopathic. Quadriceps biopsy at 2 months showed mild CN and ill-defined cores. A novel observation concerned a striking sub-population of fibres, often smaller, with circumferential rims with/without central aggregates of oxidative staining. These were designated as myofibres with subsarcolemmal rims and/or central aggregates of mitochondria (SRCAM fibres). We subsequently identified SRCAM fibres in 35.7% of genetically definite or probable/possible TTN-CM cases (10/28 total; 4/9 definite, 2/3 probable and 4/16 possible). In stark contrast, SRCAM fibres were present in only 3.6% (2/56) of cases with pathogenic variants in other core/CN-CM genes (RYR1, SEPN1, MYH7, MYH2, DNM2, MTM1). They were most frequent in neonates. Analysis of additional cases and ultrastructural characterisation is ongoing. We recommend that patients with a clinicopathological picture compatible with CM and presence of SRCAM fibres in their muscle biopsy should be screened for TTN mutations.

OC26.05: The predominance of the fetal right heart chambers in the second and third trimester

To study the reasons for the disproportion of the size of fetal heart chambers with a pronounced predominance of the right ones and the perinatal outcomes of such cases. A prospective study in the tertiary centre. Echocardiography and Doppler velocimetry were performed in 63 fetuses with a right to left ventricles ratio more than 1.5. 30 fetuses had a disproportion of the chamber size at 21-28 weeks and 33 had it after 28 weeks. The perinatal outcomes of all the cases have studied. Among the reasons for the disparity in heart chambers size up to 28 weeks there were heart defects in 16/30 (53.3%) fetuses (hypoplastic left heart 11, coarctation of the aorta 4, Ebstein's anomaly 1), 14/30 (46.7%) of fetuses had early onset IUGR. In the early imbalance of the chambers, the outcomes were as follows: pregnancy termination in 13 cases, perinatal death in 12, cardiac surgery in 3 newborns. Among the reasons for the disparity in heart size after 28 weeks there were heart defects in 5/33 (15.1%) fetuses (coarctation of aorta 2, pulmonary stenosis 2, borderline left ventricle 1). In 2 fetuses, a premature (in utero) closure of the ductus arteriosus occurred, 1 fetus had an aneurysm of the vein of Galen (AVG), 14 had a late onset IUGR. 3 fetuses appropriated for term had placental dysfunction and metabolic acidosis. In fetuses with late imbalance of chambers, the outcomes were as follows: intrauterine death 2, neonatal death 1, preterm medical indicated delivery 9. 21/33 (63.6%) of newborns did not have any birth-related problems. Predominance of fetal cardiac right chambers in the 2nd trimester is mostly associated with heart defects and early IUGR. In the 3 rd trimester the asymmetry can be associated with late onset IUGR, AVG, premature closure of the ductus arteriosus, metabolic acidosis and can also be idiopathic and have no perinatal consequences. In the 3rd trimester the outcomes are better, but the risk of perinatal loss and the neonatal morbidity exists.

Postnatal outcome of fetal isolated ventricular size disproportion in the absence of aortic coarctation.

Cardiac ventricular size disproportion is a marker for aortic coarctation (CoA) in fetal life, but approximately 50% of fetuses do not have CoA after birth. The aim of this study was to evaluate the postnatal outcome of cases with fetal ventricular size disproportion in the absence of CoA after birth. All cases with fetal isolated ventricular size disproportion diagnosed between 2002 and 2015 were extracted from a prenatal congenital heart defects regional registry. Cases were stratified according to presence or absence (non-CoA) of aortic arch anomalies after birth. Postnatal outcome of non-CoA cases was evaluated by assessing the presence of cardiac and other congenital malformations, genetic syndromes and other morbidity after birth. Non-CoA cases were further classified according to whether they had cardiovascular pathology requiring medication or intervention. Seventy-seven cases with fetal ventricular size disproportion were identified, of which 46 (60%) did not have CoA after birth. Of these, 35 did not require cardiovascular intervention or medication, whereas 11 did. Of the 46 non-CoA cases, six presented with clinical pulmonary hypertension requiring treatment after birth, cardiac defects were present in 24 cases and syndromic features were seen in four. Overall, 43% of all non-CoA children were still under surveillance at the end of the study period. The postnatal course of cases with fetal ventricular size disproportion is complicated by prenatally undetected congenital defects (46%) and pulmonary or transition problems (35%) in a significant number of cases that do not develop CoA. Proper monitoring of these cases is therefore warranted and it is advisable to incorporate the risks for additional morbidity and neonatal complications in prenatal counseling. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

The third delay: understanding waiting time for obstetric referrals at a large regional hospital in Ghana

BackgroundDelay in receiving care significantly contributes to maternal morbidity and mortality. Much has been studied about reducing delays prior to arrival to referral facilities, but the delays incurred upon arrival to the hospital have not been described in many low- and middle-income countries.MethodsWe report on the obstetric referral process at Ridge Regional Hospital, Accra, Ghana, the largest referral hospital in the Ghana Health System. This study uses data from a prospectively-collected cohort of 1082 women presenting with pregnancy complications over a 10-week period. To characterize which factors lead to delays in receiving care, we analyzed wait times based on reason for referral, time and day of arrival, and concurrent volume of patients in the triage area.ResultsThe findings show that 108 facilities refer patients to Ridge Regional Hospital, and 52 facilities account for 90.5% of all transfers. The most common reason for referral was fetal-pelvic size disproportion (24.3%) followed by hypertensive disorders of pregnancy (9.8%) and prior uterine scar (9.1%). The median arrival-to-evaluation (wait) time was 40 min (IQR 15–100); 206 (22%) of women were evaluated within 10 min of arrival. Factors associated with longer wait times include presenting during the night shift, being in latent labour, and having a non-time-sensitive risk factor. The median time to be evaluated was 32 min (12–80) for women with hypertensive disorders of pregnancy and 37 min (10–66) for women with obstetric hemorrhage. In addition, the wait time for women in the second stage of labour was 30 min (12–79).ConclusionsReducing delay upon arrival is imperative to improve the care at high-volume comprehensive emergency obstetric centers. Although women with time-sensitive risk factors such as hypertension, bleeding, fever, and second stage of labour were seen more quickly than the baseline population, all groups failed to be evaluated within the international standard of 10 min. This study emphasizes the need to improve hospital systems so that space and personnel are available to access high-risk pregnancy transfers rapidly.

Fetal Maternal Size Disproportion: Explanation for the Racial Disparity of OASIS? [7R

INTRODUCTION: Obstetric anal sphincter injuries (OASIS) are a significant complication of vaginal deliveries. Asian race is a known independent predictor of perineal trauma. Limited data demonstrate a plausible explanation of this racial disparity. We aim to assess the relationship between the fetal maternal size disproportion as measured by fetal birth weight to prepregnancy BMI ratio (BW:BMI) and OASIS in mothers of different race groups. METHODS: Retrospective cohort study of vaginal deliveries between 2006 and 2015. Demographics and obstetrical data were abstracted and compared. The significance of BW:BMI to OASIS was evaluated. Results adjusted for confounding factors. RESULTS: 16,024 vaginal deliveries were included. 28.5% had no lacerations, 64.6% had 1st or 2nd degree lacerations, and 6.9% had OASIS. Demographic factors associated with OASIS included Asian race, nulliparity, increased age, increased birth weight, episiotomy, trial of labor after cesarean, and operative vaginal deliveries. Although BMI was not an independent risk factor, BW:BMI showed a significant relationship with OASIS. For every 10 unit increase in BW:BMI, the adjusted odds of having an OASIS increased by 16% (p= < .001). After adjusting for BW:BMI, Asian race had higher OASIS rates. Interaction between race groups and BW:BMI was only significant for 1st and 2nd degree lacerations, not OASIS. CONCLUSION: This study verified known risk factors associated with OASIS. Increasing BW:BMI is associated with OASIS. However, BW:BMI does not provide insight into OASIS racial disparities; further investigations are needed to understand why Asian race is an OASIS risk factor.

Multidisciplinary Alternatives to CPAP Program for CPAP-Intolerant Patients.

Continuous positive airway pressure (CPAP) intolerance remains a persistent problem for many obstructive sleep apnea patients. Clinicians and researchers continue to search for other effective treatment modalities given the well-documented sequelae associated with untreated obstructive sleep apnea. A multidisciplinary "Alternatives to CPAP program" (ALT) can facilitate systematic evaluation of non-CPAP therapies appropriate for an individual patient. We review successful strategies and barriers encountered during implementation of an ALT at our institution. Creation of similar programs in private practice and academic settings can help medical, dental, and surgical sleep medicine specialists coordinate evaluation and treatment of CPAP-intolerant patients.

Cliff-edge model of obstetric selection in humans

The strikingly high incidence of obstructed labor due to the disproportion of fetal size and the mother's pelvic dimensions has puzzled evolutionary scientists for decades. Here we propose that these high rates are a direct consequence of the distinct characteristics of human obstetric selection. Neonatal size relative to the birth-relevant maternal dimensions is highly variable and positively associated with reproductive success until it reaches a critical value, beyond which natural delivery becomes impossible. As a consequence, the symmetric phenotype distribution cannot match the highly asymmetric, cliff-edged fitness distribution well: The optimal phenotype distribution that maximizes population mean fitness entails a fraction of individuals falling beyond the "fitness edge" (i.e., those with fetopelvic disproportion). Using a simple mathematical model, we show that weak directional selection for a large neonate, a narrow pelvic canal, or both is sufficient to account for the considerable incidence of fetopelvic disproportion. Based on this model, we predict that the regular use of Caesarean sections throughout the last decades has led to an evolutionary increase of fetopelvic disproportion rates by 10 to 20%.

HACD1, a regulator of membrane composition and fluidity, promotes myoblast fusion and skeletal muscle growth.

The reduced diameter of skeletal myofibres is a hallmark of several congenital myopathies, yet the underlying cellular and molecular mechanisms remain elusive. In this study, we investigate the role of HACD1/PTPLA, which is involved in the elongation of the very long chain fatty acids, in muscle fibre formation. In humans and dogs, HACD1 deficiency leads to a congenital myopathy with fibre size disproportion associated with a generalized muscle weakness. Through analysis of HACD1-deficient Labradors, Hacd1-knockout mice, and Hacd1-deficient myoblasts, we provide evidence that HACD1 promotes myoblast fusion during muscle development and regeneration. We further demonstrate that in normal differentiating myoblasts, expression of the catalytically active HACD1 isoform, which is encoded by a muscle-enriched splice variant, yields decreased lysophosphatidylcholine content, a potent inhibitor of myoblast fusion, and increased concentrations of ≥C18 and monounsaturated fatty acids of phospholipids. These lipid modifications correlate with a reduction in plasma membrane rigidity. In conclusion, we propose that fusion impairment constitutes a novel, non-exclusive pathological mechanism operating in congenital myopathies and reveal that HACD1 is a key regulator of a lipid-dependent muscle fibre growth mechanism.

Severe protein aggregate myopathy in a knockout mouse model points to an essential role of cofilin2 in sarcomeric actin exchange and muscle maintenance

Mutations in the human actin depolymerizing factor cofilin2 result in an autosomal dominant form of nemaline myopathy. Here, we report on the targeted ablation of murine cofilin2, which leads to a severe skeletal muscle specific phenotype within the first two weeks after birth. Apart from skeletal muscle, cofilin2 is also expressed in heart and CNS, however the pathology was restricted to skeletal muscle. The two close family members of cofilin2 – ADF and cofilin1 – were co-expressed in muscle, but unable to compensate for the loss of cofilin2. While primary myofibril assembly and muscle development were unaffected in cofilin2 mutant mice, progressive muscle degeneration was observed between postnatal days 3 and 7. Muscle pathology was characterized by sarcoplasmic protein aggregates, fiber size disproportion, mitochondrial abnormalities and internal nuclei. The observed muscle pathology differed from nemaline myopathy, but showed combined features of actin-associated myopathy and myofibrillar myopathy. In cofilin2 mutant mice, the postnatal expression pattern and turnover of sarcomeric α-actin isoforms were altered. Levels of smooth muscle α-actin were increased and remained high in developing muscles, suggesting that cofilin2 plays a crucial role during the exchange of α-actin isoforms during the early postnatal remodeling of the sarcomere.

Frequency and phenotype of patients carrying TPM2 and TPM3 gene mutations in a cohort of 94 patients with congenital myopathy

Congenital myopathies are difficult to classify correctly through molecular testing due to the size and heterogeneity of the genes involved. Therefore, the prevalence of the various genetic causes of congenital myopathies is largely unknown. In our cohort of 94 patients with congenital myopathy, two related female patients and two sporadic, male patients were found to carry mutations in the tropomyosin 2 (TPM2) and tropomyosin 3 (TPM3) genes, respectively. This indicates a low (4.3%) frequency of TPM2 and TPM3 mutations as a cause of congenital myopathy. Compared to previously described patients carrying the same mutations as found in our study (c.503G>A, and c.502C>T in TPM3, and c.415_417delGAG in TPM2), clinical presentation and muscle morphological findings differed in our patients. Differences included variation in distribution of muscle weakness, presence of scoliosis and ptosis, physical performance and joint contractures. The variation in clinical profiles emphasizes the phenotypic heterogeneity. However, common features were also present, such as onset of symptoms in infancy or childhood, musculoskeletal deformities and normal or low plasma levels of creatine kinase.One patient had nemaline myopathy and fiber size disproportion, while three patients had congenital fiber type disproportion (CFTD) on muscle biopsies. TPM2-related CFTD has only been described in two cases, indicating that mutations in TPM2 are rare causes of CFTD.

Intraoperative floppy iris syndrome (IFIS): what complication rates can we expect?

Dear Editor, In a very interesting paper, Haridas et al. have shown that patients with intraoperative floppy iris syndrome (IFIS) receiving tamsulosin or doxazosin differ in terms of morbidity rates [1]. Among 2,785 cataract operations performed in 2,028 patients, the authors identified 52 (1.9 %) cases treated with tamsulosin and 109 (3.9 %) cases in which doxazosin was administered. They compared morbidity rates between these two groups. In our opinion, however, some aspects of this study need to be discussed. In their retrospective analysis, the authors found at least one IFIS feature in 17 out of 106 eyes (16 %) from the doxazosin group and in 25 out of 52 eyes (48 %) from the tamsulosin group. Alpha-1 antagonists, used in the symptomatic treatment of benign prostatic hyperplasia, may increase the surgical difficulties and risk of iris damage, corneal edema, posterior or anterior capsule rupture, and postoperative increase in intraocular pressure [2–4]. Nevertheless, analysis of data expressed as percentages can be misleading and provide false information on the prevalence of IFIS and expected intraoperative morbidity rate. In Table 1 of their paper, Haridas et al. presented data on the size of the pupil and status of the iris in the tamsulosin and doxazosin groups [1]. However, the prevalence of various abnormalities (large or small pupil, iris prolapse, etc.) was expressed as a percentage of IFIS cases in a given group, i.e. per 25 and 17 eyes in tamsulosin and doxazosin group, respectively. In our opinion, however, the prevalence should be rather expressed per the whole group administered a given agent, i.e. per 52 and 106 eyes of patients treated with tamsulosin and doxazosin, respectively. Only in this way can we estimate the potential risk of intraoperative complications in patients treated with α-1 antagonists. Furthermore, it should be noted that expressing seven cases of intraoperative complications in the tamsulosin group as 13.5 % (7 out of 52 eyes) suggests that such morbidity can be expected in patients subjected to cataract surgeries. This is not true, as intraoperative complications documented in the tamsulosin IFIS group (iris damage – 5 cases, anterior capsule rupture – 1 case, corneal edema – 1 case) corresponded to only 0.3 % of all 2,785 operated eyes, the average rate of cataract complications in non-IFIS patients. Takmaz analyzed a group of 858 operated eyes and identified intraoperative complications in 6 eyes of patients who were treated with tamsulosin [8]. However, he emphasized the lack of significant differences in the morbidity rates of tamsulosin-treated patients with and without IFIS (p = 0.245). According to Haridas et al., patients treated with tamsulosin differed significantly from the controls in terms of the morbidity rates (13.5 %, i.e. 7 out of 52 eyes vs. 3.3 %, i.e. 5 out of 150 eyes; p = 0.014) [1]. However, we postulate that statistical analyses are not justified in the case of such a large disproportion in group size. Furthermore, this analysis was not adjusted for surgeon’s experience and other intraoperative factors. Table 1 Studies reporting the rate of intraoperative floppy iris syndrome (IFIS) complications The exact data on the type and prevalence of intraoperative complications is missing in available literature. (Table 1) Chang et al. spoke to the intraoperative use of retractors in five cases but did not provide any data on the percentage of postoperative iris damage in patients with IFIS [2]. In turn, the report by Oshika et al. not only lacks any data on postoperative morbidity rates but does not provide any information about intraoperative strategies of performing cataract phacoemulsification in patients with IFIS [6]. Concluding: Although the use of α-1 antagonists, especially tamsulosin, can constitute a potential risk of intraoperative complications in cataract surgery, such complications occur sporadically, and therefore, the morbidity rates should be presented in a uniform manner in order to avoid their inadvertent overestimation.

Incidence of Alpha-1 Antitrypsin Z and S Alleles in Patients with Granulomatosis with Polyangiitis—Pilot Study

Inherited alpha-1 antitrypsin (AAT) deficiency is one of the three most common genetic disorders in Caucasians. It considerably increases the risk of progressive obstructive lung diseases, mostly chronic obstructive pulmonary disease. It has also been suggested that AAT deficiency might be instrumental vasculitis associated with the anti-neutrophil cytoplasm antibodies (cANCA) and subsequent lung tissue injury. We present the results from a pilot study involving 51 patients with granulomatosis with polyangiitis, formerly known as Wegener's granulomatosis (GPA), 43 of whom were cANCA positive. The control group consisted of 658 individuals. AAT blood concentration assessment by nephelometry, phenotyping by isoelectrofocusing and real-time PCR genotyping were performed. Deficiency alleles PI*Z and PI*S were detected in 3 (5.88%) and in 2 patients (3.92%) with GPA, respectively. All of them were cANCA positive. In the controls, PI*Z was observed in 2.8% while PI*S in 1.5% of cases. Accordingly, the increased incidence of main deficiency alleles was demonstrated in GPA, and particularly in cANCA+GPA patients, when compared to the controls. The estimated frequency for PI*Z in GPA, cANCA+GPA patients and controls was, respectively, 29.4/1000, 34.9/1000 and 13.7/1000, whereas for PI*S it was 19.2/1000, 23.2/10,00 and 7.6/1000. However, the observed differences did not reach statistical significance due to the considerable size disproportion between groups. CONSCLUSIONS: We believe that our preliminary data confirm the clinical importance of AAT deficiency in GPA patients and the need to screen for AAT deficiency alleles. The study is on-going.

G.P.124 Fiber type disproportion caused by LMNA mutations

<h2>Abstract</h2> Mutations in the gene encoding nuclear envelope proteins of A-type lamins (<i>LMNA</i>) are known to cause Emery–Dreifuss muscular dystrophy, limb girdle muscular dystrophy type 1B, and <i>LMNA</i>-related congenital muscular dystrophy. Pathological features of <i>LMNA</i>-myopathy are nonspecific dystrophic changes including variation in fiber size, necrotic and regenerating process, and increased muscle fibers with internal nuclei. Congenital fiber type disproportion (CFTD) is a congenital myopathy pathologically designated by smaller sized type 1 fibers at least 12% than type 2 fibers with no structural abnormalities. We recently came across a <i>LMNA</i>-myopathy patient whose earlier diagnosis was CFTD. In this study, we searched for <i>LMNA</i> mutations in 94 unrelated patients pathologically diagnosed as CFTD. Genetically confirmed 29 <i>LMNA</i>-myopathy patients were also reevaluated pathologically. We identified two patients carrying a novel heterozygous <i>LMNA</i> mutation (p.Glu33del or p.Lys123del) among 94 CFTD patients. On the other hand, 5 of 29 (17%) <i>LMNA</i>-myopathy patients showed fiber type disproportion (FTD) on muscle pathology. The age at onset of the 7 <i>LMNA</i>-myopathy patients with FTD was from 1y2m to 4y (mean 2y8m) except for one adult-onset patient. None of the <i>LMNA</i>-myopathy patients with FTD had high arched palate or respiratory involvement. Serum creatine kinase levels were mildly elevated (mean 915□} 698IU/L). The ratio of fiber size disproportion (%FSD) was not significantly different between <i>LMNA</i>-myopathy withFTD and 9 CFTD patients with <i>ACTA1</i> or <i>TPM3</i> mutations. Importantly, CFTD with <i>ACTA1</i> or <i>TPM3</i> mutations showed type 1 fiber atrophy compared to age-matched controls, while <i>LMNA</i>-myopathy with FTD showed type 2 fiber hypertrophy. From our results, we encourage <i>LMNA</i> mutation analysis in CFTD patients with no high arched palate and respiratory involvement.

Postcoital Rectovaginal Fistula: A Case Report

Abstract Background: Coital trauma cases reported in the literature mostly occur in the context of sexual violence, abuse, or rape. Consenting sexual intercourse is exceptional as the origin of a rectovaginal fistula. Such a fistula might be caused by the woman's virginity or sexual abstinence, the disproportion in size between the penis and vagina, or by vaginal dryness and the repeated aggressive use of foreign objects. Case: The case of a 22-year-old African woman from Senegal who was treated for rectovaginal fistula that had occurred in the context of consenting sexual intercourse, is presented. The couple did not have any anomaly or genital malformation. The patient was admitted 2 days after her first sexual intercourse for vaginal bleeding and release of fecal matter through vaginal route. Examination of the perineum showed a low rectovaginal fistula that was treated by a one-time repair. The patient had an uneventful postoperative course and was discharged 5 days after the surgical operation. Concl...

Mutations in TPM2 and congenital fibre type disproportion

The main diagnostic feature of congenital fibre type disproportion is that type 1 fibres are consistently smaller than type 2 fibres in the absence of other histological abnormalities. Mutations in the TPM3, RYR1 and ACTA1 genes are the most common established genetic causes. There has been one previous report of congenital fibre type disproportion due to a mutation in TPM2, although some atypical histological features were present. We present two cases in which novel de novo missense mutations in TPM2 are associated with marked fibre size disproportion. The finding of typical histological changes of congenital fibre type disproportion in association with a p.Ser61Pro mutation confirms that TPM2 can cause typical congenital fibre type disproportion. Although not seen on light microscopy studies, protein inclusions typical of small 'caps' were found on electron microscopy in a second patient with a p.Ala155Val mutation in TPM2. This case emphasises the importance of electron microscopy in patients with presumed congenital fibre type disproportion, to exclude the presence of caps, nemaline bodies or minicores, which, if present, may be very helpful in guiding genetic analysis.

Comprehensive intermaxillary tooth width proportion of Bangkok residents

Proper occlusion depends on the correct width ratio between upper and lower teeth, known as Bolton's ratio. In fact, this ratio can be calculated for each pair of teeth from the central incisor to the first permanent molar. This set of ratios, known as comprehensive cumulative percentage ratios (CPRs), can be used not only to determine which tooth or teeth have a tooth width discrepancy, but can also enable the partial graphical analysis of tooth width discrepancy when there is agenesis of certain permanent teeth. Although CPRs have been calculated for Caucasians, tooth width is known to vary depending on racial origin. Therefore, a test of differences between racial groups should be carried out. If these ratios of the Caucasians and Bangkokians are significantly different, the ratio of the Bangkokians is recommended. The objective of this study was to measure tooth size disproportion for Thai patients and to calculate a corresponding set of CPRs. Thirty-seven pairs of dental models were made from a group of Bangkok residents with normal occlusion. Mesiodistal tooth width was measured for each model. The intra- and inter-examiner measurement errors were ascertained as insignificant (p > 0.05). CPRs were then calculated and compared to those derived from other studies. Ten of thirteen CPRs were significantly different from corresponding values derived from Caucasians. We conclude that tooth width ratios vary between different racial groups, and therefore that these should be calculated specifically for each patient racial group.

P1.46 Genetic, clinical, and pathological features of congenital fiber type disproportion in Japan

Background: Congenital fiber type disproportion (CFTD) is a congenital myopathy of which diagnosis is based on smaller sized type 1 fibers (fiber size disproportion [FSD]>12%; FSD=100×[mean type 2 fiber diameter−mean type 1 fiber diameter]/mean type 2 fiber diameter) with no structural abnormalities on muscle pathology. Causative mutations have been reported in three genes, α-tropomyosin slow (TPM3), skeletal muscle α-actin (ACTA1), and selenoprotein N (SEPN1). In the previous literatures, TPM3 mutations are the most common, but SEPN1 mutation was reported only in one family.