Small Thorax Research Articles

Prenatal diagnosis of recurrent Kagami–Ogata syndrome inherited from a mother affected by Temple syndrome: a case report and literature review

BackgroundKagami–Ogata syndrome (KOS) and Temple syndrome (TS) are two imprinting disorders characterized by the absence or reduced expression of maternal or paternal genes in the chromosome 14q32 region, respectively. We present a rare prenatally diagnosed case of recurrent KOS inherited from a mother affected by TS.Case presentationThe woman’s two affected pregnancies exhibited recurrent manifestations of prenatal overgrowth, polyhydramnios, and omphalocele, as well as a small bell-shaped thorax with coat-hanger ribs postnatally. Prenatal genetic testing using a single-nucleotide polymorphism array detected a 268.2-kb deletion in the chromosome 14q32 imprinted region inherited from the mother, leading to the diagnosis of KOS. Additionally, the woman carried a de novo deletion in the paternal chromosome 14q32 imprinted region and presented with short stature and small hands and feet, indicating a diagnosis of TS.ConclusionsGiven the rarity of KOS as an imprinting disorder, accurate prenatal diagnosis of this rare imprinting disorder depends on two factors: (1) increasing clinician recognition of the clinical phenotype and related genetic mechanism, and (2) emphasizing the importance of imprinted regions in the CMA workflow for laboratory analysis.

Prenatal phenotype and genetic analysis of a fetus with Fibrochondrogenesis 1 due to compound heterozygous variants of COL11A1 gene

To explore the genetic etiology of a fetus with short limbs identified by prenatal ultrasonography. A fetus detected with short limb malformations at Shengjing Hospital Affiliated to China Medical University on October 25, 2021 was selected as the study subject. Prenatal ultrasound and post-abortion imaging were carried out to determine the phenotypic characteristics of the fetus. Amniotic fluid sample of the fetus and peripheral blood samples of its parents were collected. Following extraction of genomic DNA, whole-exome sequencing was carried out. Candidate variants were verified by Sanger sequencing. Online software was used to predict the structural changes of the mutant proteins. Prenatal ultrasound showed that the fetus had a small bell-shaped thorax, markedly shortened limbs, flat midface, a small nose with anteriorly tilted nostrils, and a small mandible. Post-abortion CT showed typical short and wide fetal ribs, cupped metaphyses at both ends, short long bones with wide metaphyses, resulting in a dumbbell-shaped appearance and curved thoracic vertebrae. Whole-exome sequencing revealed that the fetus had harbored compound heterozygous variants of the COL11A1 gene, namely c.2251G>T and c.3790G>T, both of which were predicted to alter the important Gly-X-Y structure of collagen protein. Sanger sequencing confirmed that the variants were respectively inherited from its parents. A rare fetus with Fibrochondrogenesis type 1 due to compound heterozygous variants of the COL11A1 gene has been diagnosed. Above finding has enabled genetic counseling and reproductive guidance for this family.

Stem chewing lice on Cretaceous feathers preserved in amber

Phthirapteran lice (true lice or parasitic lice) are a major group of ectoparasitic insects living on their bird or mammal hosts during their entire life cycle.1 Due to their highly specialized lifestyles, they are extremely poorly represented in fossil records.2 Molecular clock estimations have speculated extensively about the origin time of parasitic lice,3,4 yet none have been confirmed unequivocally. Herein, we report a new family of stem chewing lice, based on two adult insects associated with several semiplume feathers preserved within a piece of Kachin amber from the mid-Cretaceous. They display some defining characteristics of the Amblycera, an early-diverging lineage of the crown lice group. These features include a wingless body, chewing mouthparts, narrow and small thorax, and short tarsus with elongated euplantulae. Our phylogenetic analysis places the new taxa in the Amblycera, and the discovery thus pushes back the lice fossil records by at least 55 million years. Furthermore, the new specimens show primitive characters such as compressed and club-shaped terminal segments of antennae, maxillary and labial palps, and unmodified femora of hind legs, providing key information for the evolutionary relationship between free-living booklice and parasitic lice. This suggests that some ectoparasitic characters defining the crown lice group might have evolved among amblyceran and non-amblyceran lice in parallel. These newly described fossil specimens imply at least a Cretaceous age of Phthiraptera.

Thanatophoric Dysplasia – Rare Fatal Skeletal Dysplasia Detected on Prenatal Ultrasound

Abstract Skeletal dysplasias form an assorted cluster of bone dysplasias that result in atypical and aberrant skeletal size and shape. The case discussed here was diagnosed as thanatophoric dysplasia during the second-trimester ultrasound examination and the medical termination of pregnancy was subsequently done. The fetus had shortening of the limbs (micromelia) with long bones (shaped like a telephone receiver), a small conical thorax, a protuberant abdomen, increased skin thickness with a cloverleaf skull, and macrocephaly. The relevant details and review of literature pertinent to the case are hereby discussed.

Comparison of small female PMHS thoracic responses to scaled response corridors in a frontal hub impact

Objective The purpose of this study was to generate biomechanical response corridors of the small female thorax during a frontal hub impact and evaluate scaled corridors that have been used to assess biofidelity of small female anthropomorphic test devices (ATDs) and human body models (HBMs). Methods Three small female postmortem human subjects (PMHS) were tested under identical conditions, in which the thorax was impacted using a 14.0 kg pneumatic impactor at an impact velocity of 4.3 m/s. Impact forces to PMHS thoraces were measured using a load cell installed behind a circular impactor face with a 15.2 cm diameter. Thoracic deflections were quantified using a chestband positioned at mid-sternum. Strain gages installed on the ribs and sternum identified fracture timing. Biomechanical response corridors (force-deflection) were generated and compared to scaled small female thoracic corridors using a traditional scaling method (TSM) and rib response-based scaling method (RRSM). A BioRank System Score (BRSS) was used to quantify differences between the small female PMHS data and both scaled corridors. Results Coefficients of variation from the three small female PMHS responses were less than 2% for peak force and 7% for peak deflection. Overall, the scaled corridor means determined from the TSM and RRSM were less than two standard deviations away from the mean small female PMHS corridors (BRSS < 2.0). The RRSM resulted in smaller deviation (BRSS = 1.1) from the PMHS corridors than the TSM (BRSS = 1.7), suggesting the RRSM is an appropriate scaling method. Conclusions New small female PMHS force-deflection data are provided in this study. Scaled corridors from the TSM, which have been used to optimize current safety tools, were comparable to the small female PMHS corridors. The RRSM, which has the great benefit of using rib structural properties instead of requiring whole PMHS data, resulted in better agreement with the small female PMHS data than the TSM and deserves further investigation to identify scaling factors for other population demographics.

COASY related pontocerebellar hypoplasia type 12: A common Indian mutation with expansion of the phenotypic spectrum.

Pontocerebellar hypoplasia (PCH) type 12 is a rare, perinatal lethal neurodegenerative genetic disorder caused by biallelic mutations in the COASY gene. Herein, we describe the clinical and neuroradiological profile of nine affected fetuses/neonates from five families identified with a common COASY: c.1486-3C>G biallelic variant. Four of the five families were identified after data reanalysis of unresolved, severe PCH like phenotype and the fifth family through collaboration. The common antenatal phenotype was cerebellar hypoplasia. Microcephaly, arthrogryposis, and intrauterine growth restriction were the shared postnatal findings. The neurological manifestations included seizures, poor sucking, and spasticity. Novel findings of corpus callosum agenesis, simplified gyral pattern, normal sized pons, optic neuropathy, and a small thorax are reported in this series. The allele frequency of the COASY: c.1486-3C>G variant was 0.62% in the available Asian Indian database. We describe this as a possible common Indian origin variant. To the best of our knowledge, this is the largest PCH12 series reported.

EP459: Rare clinical gene variant of SOX9: Acampomelic campomelic dysplasia

eP459: Rare clinical gene variant of SOX9: Acampomelic campomelic dysplasia

Abstract 9731: Improved Risk Stratification with Vendor Independent Coronary Calcium Scores: Data from the Multi-Ethnic Study of Atherosclerosis (mesa)

Introduction: Coronary calcium score (CCS) plays a role in cardiovascular disease (CVD) risk calculators, but also reclassifies patients when considering statin therapy. However, CCS is still calculated following the Agatston methodology as developed on electron beam tomography (EBT) in the early 1990s. EBT has been replaced by multidetector computed tomography (MDCT). It is known that CCS differs substantially between MDCT-systems from different manufacturers, which can lead to risk reclassifications for 6.5% of examined individuals Aims: Our first aim was to identify CT system specific conversion factors to calculate a vendor-neutral Agatston score (rCCS). Second, we aimed to validate rCCS risk stratification for participants of the Multi-Ethnic Study of Atherosclerosis (MESA). Methods: As a first step, we calculated conversion factors between six state-of the-art CT systems and the reference EBT system used in the MESA study. For this purpose, we scanned two calcium-containing inserts, which were placed in a small and large anthropomorphic thorax phantom. Linear regression was used to find a model which converts vendor-specific CCS to vendor-independent rCCS. As a second step, we recalculated the non-zero Agatston scores of 550 MESA participants. Following the Youden method, we calculated an optimal cut-off point for rCCS. Results: The linear model for each CT system allowed for prediction of Agatston scores as measured on the EBT system (p=0.001). rCCS for GE LightSpeed, used in MESA, was calculated as rCCS=0.049+1.97xMESA Agatston score and rCCS=1.903+1.37xMESA Agatston score for small and large size, respectively. The median MESA Agatston score was 100.5 (26.3-379.5), and the median rCCS was 135.8 (35.6-508.6). Participants were assigned to a high Agatston category with Agatston scores exceeding 100 (50.2%) and 187 (43.1%) for CCS and rCCS, respectively. The hazard ratio for CVD of individuals with high Agatston scores increased from 1.88 (95%CI: 1.31-2.68, p=0.001) with MESA scores to 2.15 (95%CI: 1.52-3.05, p=0.001) with rCCS. rCCS reclassified 39 participants into the lower risk group, without statin therapy. Conclusions: In conclusion, based on these preliminary results, rCCS may improve patient classification for statin therapy.

VP16.14: Diagnosis of short rib polydactyly syndrome type IV (Beemer‐Langer syndrome): a case report

Short rib-polydactyly syndrome (SRPS) is a rare congenital autosomal recessive inherited disease classified in four subtypes. Prenatal ultrasonography findings and postnatal examinations may help classify in one of four subtypes. We present a case of an infant who presented multiple congenital anomalies and the postnatal radiography helped to classify the SRPS as type IV (Beemer-Langer). A 23-year-old was referred for prenatal ultrasound which showed cystic hygroma, small omphalocele and choledocal cyst. Chromosomal analysis revealed a normal male karyotype. Morphological scan revealed small thorax, short ribs, micromelic shortening of limbs with the tibia slightly longer than the fibula, unilateral clubfoot, hidrocephalus and renal hiperechogenicity. Magnetic Resonance performed at 35 weeks revealed micrognathia and mesenteric lymphangioma. The infant delivered at 38 weeks of gestation and died within 60 minutes due to respiratory failure. Postmortem radiography showed marked shortening of all long bones, strikingly narrow thorax with short and horizontal ribs, highly placed clavicles, small scapulae, small ilia and the tibia was longer then the fibula. Identification of the SRPS subtype can be difficult due to overlap of clinical and pathologic findings. This case may help understanding Beemer-Langer type's phenotypic features such as micrognathia, cleft lip, hydrops, hydrocephalus and omphalocele. The most common radiological findings include narrow thorax with short ribs, short tubular bones, highly placed clavicle, small scapulae and ilia and bowing of radius and ulna with the tibia being longer than the fibula. The prognosis of Beemer-Langer syndrome is poor as infants usually die shortly after birth because of respiratory failure secondary to marked pulmonary hypoplasia.

Distrofia torácica asfixiante o Síndrome de Jeune

La distrofia torácica asfixiante (DTA), también denominada Síndrome de Jeune, es una enfermedad genética autosómica recesiva, cuya causa se desconoce en muchos casos. Sin embargo, se han identificado mutaciones en al menos 11 distintos genes.[1,2] Su frecuencia se estima en 1:130000 recién nacidos vivos.[3] La afección clínica se manifiesta en los huesos, principalmente en el tórax y las costillas. El tórax pequeño y las costillas cortas, son causa de la cavidad torácica, característicamente en “forma de campana” que, restringe el crecimiento y la expansión de los pulmones, lo que causa dificultad respiratoria.[3,4] La forma letal de este síndrome se debe a insuficiencia respiratoria secundaria a la hipoplasia pulmonar y al estrechamiento de la caja torácica.[4] La DTA se puede asociar también con brazos y piernas cortas, formas inusuales de los huesos pélvicos, dedos adicionales de pies o manos y problemas renales, cardíacos, hepáticos y oculares.[1,2,3] El objetivo es reportar un caso clínico de la forma letal de DTA.

VP13.05: Prenatal ultrasound diagnosis of fetal limb skeletal dysplasia

To explore the characteristics of fetal limb skeletal deformities by prenatal ultrasound. The prenatal ultrasound results of fetuses with skeletal dysplasia of extremities from October 2016 to January 2019 were retrospectively analysed. A total of 164 cases of abnormal limb skeletal development were detected from 12 weeks to 37 weeks of pregnancy. 15 cases presented with short and angled long bone, short ribs, small thorax, low ossification of skull, short nasal bone or abnormal spine, which were fatal skeletal malformations. There were four cases of fetal limb long bones less than -4SD and 51 cases of club foot. There were 12 cases of overlapping fingers, 4 of which were confirmed to be Trisomy 18. There were seven cases of middle phalangeal bone loss in both hands and 10 cases of dysplasia or deletion of radius with carpal abnormality. In addition, we found three cases of metacarpal and phalangeal abnormalities. Four cases of amniotic band syndrome were characterised by finger shortage, toe shortage, lower extremity abnormality, skull deformation, encephalocele, abdominal fissure, etc. A case of six fingers and six toes with bilateral fetal polycystic kidney and occipital encephalocele was confirmed as Meckel–Gruber syndrome after delivery. Two cases of cleft hand and foot were found. There were four cases of lower extremity rigidity, two cases of which were combined with femur less than -2SD, excessive amniotic fluid, mild neck edema and bilateral small lung, suspected of Pena Shokeir syndrome. One fetus was diagnosed as spinal stenosis, combined with extremely flat face and absent nasal bone. Postnatal x-ray showed that the terminal finger was short and gene chip examination showed no abnormality, which was a rare abnormality of macular achondroplasia. The common missed cases were polydactyly and syndactyly. Three-dimensional ultrasound is intuitive and can provide more information. Prenatal two-dimensional and three-dimensional ultrasound play an important role in the detection and classification of fetal limb skeletal malformations.

Pacemaker-generated stress fracture of the second rib: a case report

BackgroundPocket-related complications following the implantation of cardiovascular implantable electronic devices primarily include pocket hematoma, infection, skin erosion or decubitus, device migration, and Twiddler's syndrome, with other pathologies such as nerve impairment or bone lesions being extremely rarely encountered. We report a case of a 20-year old asthenic, non-athlete female patient presenting with a device-generated fracture of the second rib several months after sub-muscular permanent pacemaker implantation due to repeated bilateral pre-pectoral pocket infections.Case presentationA 20-year old female patient was readmitted to our institution 9 months following sub-pectoral implantation of a permanent pacemaker, complaining of severe pocket-related pain, which arose spontaneously in the absence of direct trauma, intense physical activity or vigorous coughing, and was associated with normal day-to-day activity. To rule out a pacemaker re-infection, a native computed tomography and a positron emission tomography—computed tomography of the thorax were performed. Both modalities excluded an infection but showed a healing fracture and a focus of enhanced metabolic activity in the anterolateral part of the right second rib, indicating a non-traumatic or stress fracture of the bone. Consequently, a complete extraction of the pulse generator and both leads was performed and the smallest available single-chamber pulse generator with a single atrial electrode was implanted in the sub-fascial, pre-muscular pocket in the now recovered and uninfected left subclavicular region, alleviating patient’s severe pain symptoms and significantly enhancing her quality of life.ConclusionsIn the absence of direct trauma, intense physical activity or vigorous coughing, we assume that in this asthenic girl a normal day-to-day motion of the right shoulder has persistently forced the sub-muscularly placed pulse generator toward thoracic wall, putting increased repetitive pressure force on the underlying bones, finally causing a fatigue stress fracture of the second rib. In asthenic phenotype patients with small thorax and short subclavicular distance, a sub-muscular pacemaker implantation can potentially cause unique and unexpected pocket-related adverse events necessitating advanced diagnostics and timely treatment.

Embolization of peripheral arteriovenous malformations and fistulas with precipitating hydrophobic injectable liquid (PHIL®).

This paper reports on the preliminary experience of a single center in the embolization of peripheral AVMs and fistulas with precipitating hydrophobic injectable liquid (PHIL®), focusing on technical aspects and short-term clinical outcomes. Seven males and five females were included in this study, mean age 42.16years. For ten of them, it was the first embolization treatment; two had been previously treated with Onyx® embolization. PHIL® was injected with a transarterial approach without other embolics during the same procedure. Lesions were localized in small bowel (1), colon (1), head face (5), forefoot (1), uterus (1) and thorax (3); all were symptomatic. After 30-day clinical follow-up, a contrast-enhanced CT or MR was acquired at 3months from intervention to detect eventual lesion residual. After a single embolization procedure, complete technical success was obtained in 50%, while clinical improvement without additional therapies was appreciable in all patients. No technical failure occurred; in two cases, a small amount of PHIL® proximally refluxed in nontarget vessels without clinical effects. No tattooing effects of superficial lesions neither artifacts at CT and cone-beam CT controls were evident. PHIL® seems to be a safe and effective liquid embolic agent for the treatment of peripheral AVMs and fistulas; although a direct comparison between PHIL and Onyx was not performed, PHIL might present the advantages of reduced artifacts at postprocedural CT scan and no need for shaking time preparation, but it is more expensive due to lower volume of product for each package and slightly less radiopaque at fluoroscopy.

Jeune syndrome: Asphyxiating thoracic dystrophy and its genetic diagnosis – A rare case report

Jeune syndrome, also known as asphyxiating thoracic dystrophy, is a rare multisystem potentially lethal skeletal dysplasia. It has an estimated incidence of 1/100,000–130,000 live births. A term outborn female neonate born by vaginal delivery to a primigravida mother, presented to our neonatal intensive care unit with severe respiratory distress since birth. The baby was noticed to have multiple characteristic skeletal anomalies including small bell-shaped thorax and short limbs leading to the clinical diagnosis of Jeune syndrome. Whole genome sequencing was done which confirmed the diagnosis. A correct clinical and genetic diagnosis in index cases of Jeune syndrome should be established to facilitate prenatal diagnosis and genetic counseling.

Thanatophoric Skeletal Dysplasia: A Case Report

Thanatophoric skeletal dysplasiais the most lethal, rare, sporadic birth defect due to de novo mutation in the fibroblast growth factor receptor-3. Clinically this is characterized by shortening of the limbs (micromelia), small conical thorax, flat vertebral bodies and macrocephaly at birth. We encountered a similar case with ultrasonographic findings suggestive of Thanatophoric Skeletal Dysplasia which resulted in the death of the baby within an hour of birth. Almost all cases of this condition have been reported to have died interuterinally or a few days after birth.

Kagami\u2013Ogata syndrome in a fetus presenting with polyhydramnios, malformations, and preterm delivery: a case report

BackgroundKagami–Ogata syndrome is also known as paternal uniparental disomy 14 and related disorders and is caused by abnormal genomic imprinting in the long arm of the chromosome 14q32.2 region. Its clinical manifestations include polyhydramnios in the fetal stage, respiratory insufficiency because of a small thorax, abdominal wall abnormalities, and peculiar facial features after birth.Case presentationA 38-year-old Japanese primigravida woman was referred to our hospital in the 19th week of pregnancy for suspected omphalocele. She had a history of hypothyroidism but was prescribed orally administered levothyroxine (50 μg/day) prior to conception and was euthyroid. Her ultrasound scan prior to visiting our hospital revealed fetal omphalocele, heavy for date, and polyhydramnios. The mother was advised to be admitted for observation from 28 weeks of gestation for threatened premature delivery. She required amniodrainage at 29 and 32 weeks of gestation. At 35 weeks of gestation, the fetal membrane prematurely ruptured and she gave birth after an emergency Cesarean section. The infant was a male child with a birth weight of 3188 g, and was suspected to have Kagami–Ogata syndrome after birth based on thoracic hypoplasia, swallowing function abnormalities, and peculiar facial features. A definitive diagnosis was established by performing genetic testing of the infant after obtaining informed written consent from both the parents; the results of the genetic testing revealed hypermethylated intergenic-differentially methylated region and maternally expressed gene 3-differentially methylated region in the corresponding chromosome 14 region. Both the parents were genetically tested after adequate genetic counseling, which revealed a de novo microdeletion in a differentially methylated region.ConclusionKagami–Ogata syndrome should have been suspected because of the presence of polyhydramnios and omphalocele during pregnancy. Respiratory insufficiency soon after birth, because of a small thorax, is expected in this disease and a diagnosis during pregnancy may have enabled appropriate care after birth.

X-linked dominant chondrodysplasia punctata 2 with severe phenotype in one female fetus: a case report

We reported a female fetus diagnosed with X-linked dominant chondrodysplasia punctata 2 with severe phenotype. The fetus was found with abnormal short limbs, thick metaphysis on the right lower limb and a narrow and small thorax by prenatal ultrasound at 24+5 weeks of gestation. Non-invasive prenatal test indicated the risks of trisomies 21, 18 and 13 were low. The pregnancy was terminated at 27 weeks of gestation and postnatal X-ray imaging showed that the fetus had short femur and humerus, a narrow and small thorax, thickened metaphysis with a splashed paint spot pattern, and asymmetric shortened lower limbs. Whole-exome analysis showed that the fetus carried a heterozygous pathogenic mutation c.440G>A (p.Arg147His) in the EBP gene. The mutation was confirmed to be a de novo mutation as neither of her parents carried the same mutation. Thus, the patient was diagnosed as having X-linked dominant chondrodysplasia punctata 2. The severe phenotype of this case migh be related to random X chromosome inactivation. Key words: Chondrodysplasia punctata; Ultrasonography, prenatal; Whole exome sequencing; Female

Full wave 3D inverse scattering: 21st century technology for whole body imaging

Quantitative high resolution (QHR) images of speed of sound and attenuation in human breast have been made using full wave inverse scattering in three-dimension (FWIS3D), where only soft tissue is present. The FWIS3D technology and method are reviewed. Recent QHR images in the presence of bone and gas have been obtained with FWIS3D and are shown. Transmission mode quantitative and refraction corrected reflection images of small piglet abdomen, thorax, and head are shown. QHR images of the human knee using the same technology are shown. Human Knee is difficult due to the predominant presence of bone. With low frequency FWIS3D, the meniscus, structure within the Femur-Tibia (F-T) space, ligaments, and the infrapatellar fat pad can be seen. The intra-condyle space in the Femur is visible. It was earlier established that 3D modelling was necessary for breast. It is shown to be even more important for F-T space and whole body imaging. Quantitative estimates of high speed early development bone are made, and imaging through neo-natal skull is performed. Clear correspondence with known structures even in the presence of gas is displayed. This reveals FWIS3D ultrasound tomography as a 21st century whole body imaging modality.

Thanatophoric skeletal dysplasia: A case report

Thanatophoric skeletal dysplasiais the most lethal, rare, sporadic birth defect due to de novo mutation in the fibroblast growth factor receptor-3. Clinically this is characterized by shortening of the limbs (micromelia), small conical thorax, flat vertebral bodies and macrocephaly at birth. We encountered a similar case with ultrasonographic findings suggestive of Thanatophoric Skeletal Dysplasia which resulted in the death of the baby within an hour of birth. Almost all cases of this condition have been reported to have died interuterinally or a few days after birth.

Fetal thanatophoric dysplasia

Thanatophoric dysplasia (TD) is a rare autosomal dominant lethal skeletal dysplasia with two subtypes. Mutations in the fibroblast growth factor receptor 3 gene (FGFR3) results in both subtypes. In prenatal diagnosis of TD by three-dimensional ultrasound examination in second trimester aids in visualizing facial features and other soft tissue findings such as cloverleaf skull, very short extremities and small thorax. Most of the affected fetuses die in utero or shortly after birth due to either respiratory insufficiency or brain stem compression or combination of both. We report one such rare case of type I TD encountered at 32 weeks of gestational age.