Symmetrical Shortening Research Articles

Role of tectonic burial and temperature on the inversion of inherited extensional basins during collision

AbstractThe style of inversion of inherited extensional basins in the Western Alps is investigated through thermo-mechanical modelling. Two-dimensional models consist of a half-graben embedded in a relatively strong crust (basement) and filled with weak syn-rift sediments (cover). We investigate the relative influence of the internal friction (µ) of the basin-bounding normal fault, tectonic burial (h) under an overlying nappe and the geothermal gradient. We use a viscoplastic model with symmetrical shortening. The inherited normal fault is implemented as a curved thin body with a variable friction coefficient (µ) ranging from 0.1 to 0.6. The style of basin inversion is controlled at shallow depth by the internal friction coefficient, whose influence decreases with the increase of both burial depth and geothermal gradient. With increasing burial and/or geothermal gradient, fault reactivation is inhibited and distributed deformation in the basement induces the vertical extrusion of the cover. The basin inversion is accompanied by distributed deformation in the cover and by the shearing of the basin and basement interface. The results are consistent with the style of inversion of inherited half-grabens in the external Western Alps, where no significant fault reactivation occurred owing to tectonic burial underneath the Alpine internal units during the early Alpine collision.

Hexasomy 13q31.3q34 due to two marker chromosomes with inverted duplication in a fetus with increased nuchal translucency

Small supernumerary marker chromosomes are structurally rearranged chromosomes that can be formed from different chromosomal fragments and cannot be identified using chromosomal banding analysis. Their examination has to be complemented by additional analyses like fluorescent in situ hybridization or array comparative genomic hybridization. We report on partial hexasomy of chromosome 13q in a fetus of a pregnant woman referred to genetic counseling because of increased fetal nuchal translucency and increased risk of trisomy 21 and trisomy 18 in first-trimester combined prenatal screening. Using chromosome banding analysis, in situ hybridization and array comparative hybridization we revealed the presence of two marker chromosomes with inverted duplication resulting in hexasomy of a 22.6 Mbp fragment in chromosomal region 13q31.3-13q34 with the lack of chromosome 13 centromere. The fetus presented dysmorphic facial features, head and body disproportion, wide neck, ambiguous genitalia, incorrect position of the anus, and symmetrical shortening of the long bones were present in our described case. Some of these features were in accordance with other published cases. Other most often described features in tetrasomy were: microphtalmia or other major eye defects, ear abnormalities and deafness, hemangiomata, hypotelorism, severe learning disability and seizures. Despite a low risk of recurrence for small supernumerary marker chromosomes the possibility of germ line mosaicism exists, thus genetic counseling was offered to the examined family. A full characterization of small supernumerary marker chromosomes in fetal karyotype is necessary for pregnancy prognosis and genetic counseling.

Case report on short limb dwarfism - Rhizomelic chondrodysplasia punctata

We are reporting a case of rhizomelic chondrodysplasia punctata, which is a rare form of peroxisomal disorder. It is an autosomal recessive disorder with distinct clinical phenotype of dwarfism due to symmetrical shortening of the proximal long bones (rhizomelia), cataracts and specific radiological abnormality like punctate epiphyseal calcification. [1] A Hindu male baby, born at term (40 weeks) by vaginal delivery, had a weak cry at birth referred to Neonatal Intensive Care Unit for fast breathing. Baby had proximal shortening of upper limbs and lower limbs. Other dysmorphic features included depressed nasal bridge, broad nose, coarse facial features, long philtrum, and macrostomia. Baby had contractures at thigh and elbow. On ophthalmological examination, there was bilateral megalocornea and near mature cataract.

Bilateral short fourth metacarpal and metatarsal in a case of idiopathic primary hypoparathyroidism

A case of bilateral symmetrical shortening of fourth metacarpal and metatarsal bones in a 25 year old female is described. She initially presented with symptoms of hypocalcaemia. Metabolic and endocrine work up concluded the underlying disorder to be idiopathic primary hypoparathyroidism contrary to the belief of psedohypoparathyroidism. The function of hand and feet were normal without any discomfort. So treatment of only hypocalcaemia was done and metacarpal, metatarsal lengthening seemed unnecessary.

Fahr's Disease: Pediatric Presentation of a Rare Neurodegenerative Disorder (IN10-1.008)

Objective: Fahr9s disease is a well-described neurodegenerative disorder in adults, but few reports describe it in pediatric patients. We present two children with Fahr9s disease. Background Fahr9s disease is a rare progressive disorder characterized by idiopathic bilateral calcification of the basal ganglia. The underlying etiology is unknown. Patients typically exhibit a movement disorder and psychiatric symptoms. Diagnosis is based on characteristic imaging findings and the exclusion of systemic causes of secondary basal ganglia calcification. Design/Methods: We describe two teenagers who presented to an academic center with neurologic complaints, and who were diagnosed with Fahr9s disease. Results: Case one. DJ is a 14 year old girl with a two year history of slowly progressive movement disorder characterized by dystonia, poor balance and bradykinesia, and progressive psychiatric symptoms of aggression and impulse control disorder. Brain MRI showed symmetrical T2 shortening in bilateral globus pallidi. Head CT showed heavy mineralization within bilateral globus pallidi consistent with calcium deposits. Systemic causes of secondary basal ganglia calcification were ruled out, and family history was non-contributory. Case two. TU is a 14 year old boy with a two year history of severe anxiety and difficulty with social interactions. He recently developed simple motor tics, but has no other movement disorder. Head CT showed bilateral calcifications in the deep grey nuclei, mostly within globus pallidi, but also involving the thalamus and white matter. Brain MRI confirmed the presence of bilateral mineralization within bilateral globus pallidi. Systemic causes of secondary basal ganglia calcification were ruled out, and family history was non-contributory. Conclusions: Fahr9s disease, a neurodegenerative disorder typically diagnosed in late adulthood, has rarely been described in children. We present two teenagers with classic clinical and radiographic features of Fahr9s disease. Children with a movement disorder and psychiatric symptoms should be evaluated for Fahr9s disease. Disclosure: Dr. Singhal has nothing to disclose. Dr. Van Haren has nothing to disclose. Dr. Wu has nothing to disclose.

Reply

We thank Drs Salomon and Bernard for their interest in our paper. In fetuses with a short femur, the outcome was primarily dependent on the coexistence of other abnormalities. So, while the risk of an underlying skeletal dysplasia, genetic syndrome or chromosomal abnormality was high in fetuses with non-isolated short femur, no such outcomes were found in fetuses in which the short femur was isolated (defined as bilateral and symmetrical shortening of the femur in the absence of associated fetal abnormalities). We would therefore like to qualify their statement that ‘One should not fear such a high incidence of abnormalities when finding an isolated short femur in a first-trimester screened woman.’ In such cases with isolated short femur we showed that in about half the cases this will remain unexplained (defined as cases in which intrauterine growth restriction (IUGR) did not develop, or no postnatal diagnosis of skeletal dysplasia or genetic abnormality was made), in about 10% of the cases subsequent re-measurement will find the femur length to be within the normal range, while in the remainder (about 40%) severe IUGR will develop (defined in our study as fetal abdominal circumference below the 5th centile with abnormal fetal umbilical artery Doppler requiring delivery before 37 weeks). Uterine artery Doppler was a useful tool in predicting which pregnancies were at particular risk of subsequent severe IUGR and associated pre-eclampsia and abruption. We agree that the referral population was likely to be biased to some degree, and in the discussion we highlight this: ‘One of the limitations of this study is that there may have been a degree of referral bias. This, in combination with the policy of first-trimester screening for chromosomal abnormalities, may change the relative proportions of pregnancy outcomes. However, the outcomes in each group will be similar…’. In other words, the proportion of isolated to non-isolated short femur may be higher, but the relative proportions of outcomes within these two groups should be similar to those that we report; this is of particular relevance in the isolated group. On the issue of normal ranges, we regret that Salomon and Bernard felt that these were discussed inadequately, and the reference for these is given (reference 7). Some light research would have shown that the population from which these normal ranges were constructed was from the same geographical area as that of our hospital (the two main hospitals are fewer than 10 km apart and have overlapping catchment areas2). We therefore believe that the reference charts used do fit our practice. We accept the importance of providing locally relevant normal ranges. However, one could question from how narrow a geographical area such ranges need to come to be sufficiently accurate, and whether using ranges derived from a very narrow segment of the population can be generalized sufficiently for use. Regarding identification of cases, as we explain in the methods (Page 508): ‘we performed a search of our computerized database in order to identify all cases of short femur diagnosed between 18 and 24 weeks of gestation during the study period’, and this is what was done. Given the likely appropriate charts, it is difficult for us to hypothesize why the number of pregnancies with a femur length < 5th centile was lower than expected. One possible explanation is that sonographers with ‘real time’ charts (i.e. when measurements are plotted on a chart at the time of the scan, as is the case in the referring units) may be more likely to re-measure and ‘normalize’ values that are borderline, when the finding is isolated. As our population was screened previously by first-trimester nuchal translucency measurement it is also likely that the most severe cases associated with chromosomal abnormalities or multiple abnormalities had undergone pregnancy termination before the time of the anomaly scan. Finally, we were impressed with the ability of the authors to back-calculate the number of scans needed, and were amused to find that we may be doing fractions of scans! A. T. Papageorghiou*, N. Fratelli*, A. Bhide*, B. Thilaganathan*, * St George's Hospital, Fetal Medicine Unit, Lanesborough Wing, Blackshaw Road, London SW17 0QT, UK

Campomelic Dysplasia

Campomelic dysplasia is a rare congenital skeletal disorder. It is an autosomal dominant condition caused by mutation of the SOX9 gene on chromosome 17. Many different body systems can be harmfully affected, resulting in a variety of skeletal and extraskeletal anomalies attributable to the gene mutation. The most evident characteristics of the condition are symmetrical shortening and anterior bowing of the femurs and tibias. For most affected fetuses, death occurs in the fetal period or in the neonatal period shortly after birth. The primary cause of death is respiratory distress due to many possible factors such as micrognathia and hypoplastic chest cavity, lungs, or airways. Fetal sonography is fundamental in the detection of related defects and the ultimate diagnosis of the disorder.

Epstein-Barr virus-associated smooth muscle tumours in a patient with an immuno-osseous dysplasia

A term female baby born via a normal delivery to consanguinous parents, presented with a lower respiratory tract infection in the neonatal period. At this time the patient was noted to have a low white cell count associated with short limbs. Immunological investigation revealed lymphopenia and markedly reduced lymphocyte proliferation in keeping with a T-cell immunodeficiency. This episode of lower respiratory tract infection responded well to antibiotic therapy and the patient remained well until 15 months of age. At 15 months of age the patient developed jaundice and was noted to have haemoglobin of 3.0 g/dl, which was treated with transfusion. Laboratory indices revealed an autoimmune haemolytic anaemia. This caused repeated anaemic episodes, requiring blood transfusions on multiple occasions. In an attempt to control the autoimmune haemolytic anaemia, therapy in the form of cyclosporin A and steroids were commenced. The autoimmune haemolytic anaemia was controlled on this regimen until the age of 3 years when it was noted that the patient was developing increasing abdominal distension and breathlessness. Plain film radiography of the limbs was performed to investigate the nature of her limb shortening, which demonstrated generalized osteopenia, delayed bone age and symmetrical limb shortening. The metaphyses were noted to be flared, with under modelled, wide diaphyses and wide ribs. In the hands ivory and cone-shaped epiphyses were seen. These features were consistent with an immuno-osseous dysplasia, most likely to be metaphyseal chondrodysplasia McKusick type (Figs. 1 and 2). An abdominal ultrasound was performed which showed hepatomegaly, with multiple well-defined reduced reflectivity focal lesions throughout both liver lobes, which were hypovascular on colour Doppler. No biliary dilatation was seen and the remaining abdominal viscera had a normal ultrasound appearance. Owing to her breathlessness a chest radiograph was performed which revealed a right lower zone soft-tissue density. Computed tomography (CT) of the thorax was then performed, demonstrating multiple soft-tissue density masses within the lungs. Percutaneous biopsy of both a chest lesion and a liver lesion was performed, revealing the lesions to be leiomyomata. The tumours were demonstrated to be positive for EBV using insitu hybridization (Figs. 3–5). This case presents a grave dilemma for future management. The optimal treatment for the congenital immunodeficiency and auto-immune haemolytic anaemia is ablation of the native bone marrow, followed by bone marrow transplant. The danger of this treatment strategy in this patient is the risk of unchecked proliferation of further smooth muscle tumours, which could become overwhelming. In patients with solitary EBV-associated leiomyomata, surgical excision is a viable option. In this patient with mutiple EBV-driven leiomyomata this is not a treatment option. Currently the patient is not receiving treatment for the tumours, and they are not rapidly progressing.

Mutational Spectrum in the PEX7 Gene and Functional Analysis of Mutant Alleles in 78 Patients with Rhizomelic Chondrodysplasia Punctata Type 1

Rhizomelic chondrodysplasia punctata (RCDP) is a genetically heterogeneous, autosomal recessive disorder of peroxisomal metabolism that is clinically characterized by symmetrical shortening of the proximal long bones, cataracts, periarticular calcifications, multiple joint contractures, and psychomotor retardation. Most patients with RCDP have mutations in the PEX7 gene encoding peroxin 7, the cytosolic PTS2-receptor protein required for targeting a subset of enzymes to peroxisomes. These enzymes are deficient in cells of patients with RCDP, because of their mislocalization to the cytoplasm. We report the mutational spectrum in the PEX7 gene of 78 patients (including five pairs of sibs) clinically and biochemically diagnosed with RCDP type I. We found 22 different mutations, including 18 novel ones. Furthermore, we show by functional analysis that disease severity correlates with PEX7 allele activity: expression of eight different alleles from patients with severe RCDP failed to restore the targeting defect in RCDP fibroblasts, whereas two alleles found only in patients with mild disease complemented the targeting defect upon overexpression. Surprisingly, one of the mild alleles comprises a duplication of nucleotides 45-52, which is predicted to lead to a frameshift at codon 17 and an absence of functional peroxin 7. The ability of this allele to complement the targeting defect in RCDP cells suggests that frame restoration occurs, resulting in full-length functional peroxin 7, which leads to amelioration of the predicted severe phenotype. This was confirmed in vitro by expression of the eight-nucleotide duplication-containing sequence fused in different reading frames to the coding sequence of firefly luciferase in COS cells.

Chondrodysplasia Punctata

Ten cases of chondrodysplasia punctata seen at the Royal Alexandra Hospital for Children between 1935 and 1972 were reviewed. According to the classification of Spranger et al., 2 are of the rhizomelic and 7 of the Conradi-Hünermann type. The tenth patient, radiographed at 17 months of age, shows, in addition to the changes characterized by the Conradi-Hünermann type, symmetrical shortening of the humeri, slight ossification disturbances of the metaphyses of the long bones of the lower extremities and humeri, shortening of the vertebral column with coronally cleft vertebrae, and flaring of the iliac wings. The authors are uncertain as to whether it represents the Conradi-Hünermann type, a milder form of the rhizomelic type, or a third type of the disorder.

Regional contraction patterns in the normal and ischemic left ventricle in man

An angiographic method is introduced that permits detection and quantification of regional disorders of ventricular wall motion in man. The left ventricle is visualized as a muscular cone suspended freely from the atrioventricular ring. This ring, outlined partially by a coronary sinus catheter, serves as a fixed plane of reference for the motion of endocardial segments during systole. Regional motion of the left ventricle is analyzed by plotting the displacement of the apex and 6 hemiaxes during 4 sequential phases of systole. The nonischemic left ventricle (6 patients) revealed synchronous and symmetrical shortening of all segments. The middle and apical hemiaxes of the posterior wall shortened to a greater extent (62 and 70 percent, respectively) than the anterior wall segments (40 to 45 percent), and there was a slight angular displacement (5 °) of the apex toward the anterior wall. Of the ischemic hearts, 6 with predominant right coronary arterial lesions demonstrated posterior akinesis and dyskinesis during early systole and an exaggerated shortening, particularly in the posteroapical segment, during late systole. These findings were associated with a significant apical displacement (23 °) toward the wall opposite the ischemic zone. Six patients with major occlusive disease of the left anterior descending artery showed the same abnormal segmental pattern in an opposite direction. The study provides a simple technique for examining and quantitating localized disorders of wall motion, and the data indicate an association between the sites of major coronary occlusions and characteristic patterns of regional contraction.

Thanatophoric dwarfism II.

A ‘new’ type of lethal bone osteochondrodysplasia — Thanatophoric Dwarfism II — is described. — Symmetrical shortening of both the trunk and extremities and coarse facial features are the most important morphologic findings. The fetuses are stillborn, premature, or die soon after the birth. In radiographic examination some shortening of the long and tubular bones with flaring, cupping and irregularity of the metaphyseal areas is present. The ischial and pubic bones are unossified but in contrast the iliac bones are fairly well developed and show triradiate acetabular roofs. The vertebral column in the lateral projection shows a wide ossification gap between the vertebral bodies and vertebral arches. Anterior shortening and flaring of the ribs is present. The ossification of the cranium and clavicles is grossly normal. Thanatophoric Dwarfism II is usually confused with Achondrogenesis as described by Parenti. Further diagnostic difficulties may arise with Thanatophoric Dwarfism of Maroteaux and Achondroplasia. — The authors point out that more types of lethal osteochondrodysplasias exist.

Hemodynamic Effects of Exercise in Isolated Valvular Aortic Stenosis

Hemodynamic data, including simultaneously measured left ventricular and aortic pressures, were obtained from 20 patients with isolated valvular aortic stenosis at rest and during supine leg exercise. Changes in left ventricular end-diastolic pressure during exercise were not significantly related to the severity of aortic stenosis but were correlated with age; patients with abnormal left ventricular end-diastolic pressures during exercise were significantly older than those in whom this variable remained normal. Exercise resulted in significant increases in both the mean rate of systolic aortic blood flow and the mean systolic pressure gradient across the aortic valve. Analysis of this pressure gradient demonstrated symmetrical shortening of the ejection time per beat with an increase of the maximal systolic pressure gradient during exercise. Although changes in mean systolic aortic pressure gradient and mean aortic flow were significantly positively correlated, the increases in mean systolic pressure gradient during exercise were less than predicted from corresponding increases in mean aortic flow; thus the result was an apparent increase in computed aortic valve area.

Physiological and morphological properties of motoneurones in the central nervous system of the leech.

1. A number of motor cell bodies have been identified in the segmental ganglia of the ventral nerve cord of the medicinal leech. These motoneurones supply either excitatory or inhibitory innervation to the muscles in the body wall.2. Several tests were made to establish that each of the identified motoneurones directly innervates muscle fibres. (a) By injecting a fluorescent dye into the cell bodies of motoneurones, their axons were traced through one or both contralateral roots. (b) Electrical stimulation of a motoneurone by an intracellular electrode caused a single nerve impulse to travel through the roots to the muscles where it set up an excitatory or an inhibitory junctional potential. (c) Impulses set up in the roots were conducted antidromically to the cell body. (d) If the preparation was bathed in 20 mM-Mg(2+), which blocks chemical synapses, conduction from the cell body to the muscles was not interrupted. Thus it is unlikely that an interneurone was interposed in the pathway within the ganglion.3. Fourteen pairs of excitatory cells and three pairs of inhibitory cells can be identified in each of the twenty-one segmental ganglia. These neurones together supply the five different muscle layers in each segment which execute the movements of the leech. Each neurone innervates a territory of muscle fibres which has a consistent size and location from segment to segment. Several lines of evidence suggest that the identified cells form a major fraction of the total number of excitatory motoneurones in the ganglion.4. The territories of the motoneurones are arranged in a quilt-like pattern closely resembling that already found for the receptive fields of sensory cells on the skin. Within the longitudinal muscle sheet, individual cells supply narrow or wide strips. The firing of each cell thus could produce bending of the segment in various directions or symmetrical shortening of it, depending on which of the motoneurones were active.5. It is possible to deduce which motoneurones are firing to produce a particular movement of the animal. Thus these experiments provide a basis for studying reflex integration between motoneurones and the identified mechanosensory cells in the ganglion.

Bilateral humerus varus; with report of a case.

Humerus varus is a comparatively rare condition. A case of bilateral humerus varus occurring in an adult African male therefore seems worthy of publication. A Ganda male, aged about 30 years, was admitted to Mulago Hospital, Kampala, with chronic gonorrhoea. It was noticed that he had symmetrical shortening of the upper arms and that he walked with a slight limp. He gave several contradictory histories, but he dated his limp from a fall at about the age of seven years. He also stated that the condition became worse at the age of about 12. He did not appear to take any notice of the deformity of his upper limbs and could give no account of them. On examination he was rather more muscular than the average Ganda male, with very prominent biceps and deltoids on both sides (Fig. 1). Measurements showed a symmetrical shortening of the humeri, the distance from the tip of the acromion to the internal epicondyle being 9¾ in. on both sides. The heads of the humeri could be palpated in the axillary fossae. The fore...