Reliability of a New Digital Tool for Photographic Analysis in Quantifying Body Asymmetry in Scoliosis.

Background: Advancements in non-ionizing methods for quantifying spinal deformities are crucial for assessing and monitoring scoliosis. In this study, we analyzed the observer variability of a newly developed digital tool for quantifying body asymmetry from clinical photographs. Methods: Prospective observational multicenter study. Initially, a digital tool was developed using image analysis software, calculating quantitative measures of body asymmetry. This tool was integrated into an online platform that exports data to a database. The tool calculated 10 parameters, including angles (shoulder height, axilla height, waist height, right and left waistline angles, and their difference) and surfaces of the left and right hemitrunks (shoulders, waists, pelvises, and total). Subsequently, an online training course on the tool was conducted for twelve observers not involved in its development (six research coordinators and six spine surgeons). Finally, 15 standardized back photographs of adolescent idiopathic scoliosis patients were selected from a multicenter image bank, representing various clinical scenarios (different age, gender, curve type, BMI, and pre- and postoperative images). The 12 observers measured the photographs at two different times with a three-week interval. For the second round, the images were randomly mixed. Inter- and intra-observer variabilities of the measurements were analyzed using intraclass correlation coefficients (ICCs), and reliability was measured by the standard error of measurement (SEM). Group comparisons were made using Student's t-test. Results: The mean inter-observer ICC for the ten measurements was 0.981, the mean intra-observer ICC was 0.937, and SEM was 0.3-1.3°. The parameter with the strongest inter- and intra-observer validity was the difference in waistline angles 0.994 and 0.974, respectively, while the highest variability was found with the waist height angle 0.963 and 0.845, respectively. No test-retest differences (p > 0.05) were observed between researchers (0.948 ± 0.04) and surgeons (0.925 ± 0.05). Conclusion: We developed a new digital tool integrated into an online platform demonstrating excellent reliability and inter- and intra-observer variabilities for quantifying body asymmetry in scoliosis patients from a simple clinical photograph. The method could be used for assessing and monitoring scoliosis and body asymmetry without radiation.

Erratum: Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum.

[This corrects the article DOI: 10.3389/fgene.2023.1198821.].

Case report: atypical Silver-Russell syndrome patient with hand dystonia: the valuable support of the consensus statement to the wide syndromic spectrum.

The amount of Insulin Growth Factor 2 (IGF2) controls the rate of embryonal and postnatal growth. The IGF2 and adjacent H19 are the imprinted genes of the telomeric cluster in the 11p15 chromosomal region regulated by differentially methylated regions (DMRs) or imprinting centers (ICs): H19/IGF2:IG-DMR (IC1). Dysregulation due to IC1 Loss-of-Methylation (LoM) or Gain-of-Methyaltion (GoM) causes Silver-Russell syndrome (SRS) or Beckwith-Wiedemann syndrome (BWS) disorders associated with growth retardation or overgrowth, respectively. Specific features define each of the two syndromes, but isolated asymmetry is a common cardinal feature, which is considered sufficient for a diagnosis in the BWS spectrum. Here, we report the case of a girl with right body asymmetry, which suggested BWS spectrum. Later, BWS/SRS molecular analysis identified IC1_LoM revealing the discrepant diagnosis of SRS. A clinical re-evaluation identified a relative macrocephaly and previously unidentified growth rate at lower limits of normal at birth, feeding difficulties, and asymmetry. Interestingly, and never previously described in IC1_LoM SRS patients, since the age of 16, she has developed hand-writer's cramps, depression, and bipolar disorder. Trio-WES identified a VPS16 heterozygous variant [NM_022575.4:c.2185C>G:p.Leu729Val] inherited from her healthy mother. VPS16 is involved in the endolysosomal system, and its dysregulation is linked to autosomal dominant dystonia with incomplete penetrance and variable expressivity. IGF2 involvement in the lysosomal pathway led us to speculate that the neurological phenotype of the proband might be triggered by the concurrent IGF2 deficit and VPS16 alteration.

Laterality in Horse Training: Psychological and Physical Balance and Coordination and Strength Rather Than Straightness.

For centuries, a goal of training in many equestrian disciplines has been to straighten the horse, which is considered a key element in achieving its responsiveness and suppleness. However, laterality is a naturally occurring phenomenon in horses and encompasses body asymmetry, motor laterality and sensory laterality. Furthermore, forcibly counterbalancing motor laterality has been considered a cause of psychological imbalance in humans. Perhaps asymmetry and laterality should rather be accepted, with a focus on training psychological and physical balance, coordination and equal strength on both sides instead of enforcing "straightness". To explore this, we conducted a review of the literature on the function and causes of motor and sensory laterality in horses, especially in horses when trained on the ground or under a rider. The literature reveals that body asymmetry is innate but does not prevent the horse from performing at a high level under a rider. Motor laterality is equally distributed in feral horses, while in domestic horses, age, breed, training and carrying a rider may cause left leg preferences. Most horses initially observe novel persons and potentially threatening objects or situations with their left sensory organs. Pronounced preferences for the use of left sensory organs or limbs indicate that the horse is experiencing increased emotionality or stress, and long-term insufficiencies in welfare, housing or training may result in left shifts in motor and sensory laterality and pessimistic mentalities. Therefore, increasing laterality can be regarded as an indicator for insufficiencies in housing, handling and training. We propose that laterality be recognized as a welfare indicator and that straightening the horse should be achieved by conducting training focused on balance, coordination and equal strength on both sides.

Cutis marmorata telangiectatica congenita being caused by postzygotic GNA11 mutations.

Cutis marmorata telangiectatica congenita (CMTC) is characterized by coarse-meshed capillary malformations arranged in asymmetrically distributed patches. The disorder may be associated with hyper- or hypoplastic limbs, syndactyly, cleft palate, and glaucoma. Because the disease usually occurs sporadically, the concept of a lethal mutation surviving by mosaicism was proposed about 30 years ago. Here we describe three children with CMTC due to a postzygotic GNA11 mutation c547C > T (p.Arg183Cys), documented in saliva (patient 1) or lesional cutaneous tissue (patients 2 and 3). All three individuals had widespread and asymmetric CMTC which was present from birth and became fainter during the first years of life. Variably associated anomalies included glaucoma, choroidal capillary malformation, and body asymmetry. In previous case reports, postzygotic GNA11 mutations were documented in two cases of phacomatosis cesiomarmorata, being characterized by CMTC coexisting with segmental dermal melanocytosis. Moreover, postzygotic GNA11 mutations were noted in two CMTC patients described under the incorrect diagnosis of "nevus vascularis mixtus". Hence, the present cases convincingly support the concept that CMTC can be caused by mosaic GNA11 mutations and thus belongs to the GNA11-Related Capillary Nevus (GNARCAN) spectrum. In two other bona fide cases of CMTC, however, we were unable to find a mutation in GNA11, which may be explained either by our inability to detect a very low percentage of mutant cells or by genetic heterogeneity of the phenotype.

Screening Procedure for Hemihypertrophy: Preliminary Results of International Multicenter Prospective Study.

INTRODUCTION: Isolated or congenital hemihypertrophy is a rare disorder characterized by asymmetric overgrowth of one side of the body. This article describes the protocol and preliminary results of a lateral body asymmetry (hemihypertrophy) screening procedure performed in healthy adolescents in a multicenter study. The reported incidence of hemihypertrophy varies between different publications and standardized protocols are needed to improve research in this area. METHODS: Our screening program is taking place in Australia, Israel, Mexico, Ukraine and USA. Procedure includes two steps: (1) "three measurements - three questions" screening, or assessment of face, palms, and shins; (2) in-depth assessment of selected cases in order to exclude localized, lesional, and syndrome-related cases as well as body asymmetry within normative range and to select suspected cases of isolated hemihypertrophy. This step includes measurements of various anatomical regions and a detailed questionnaire. RESULTS: At this stage, the screening procedure is completed and the selected participants are advised to refer to medical institutions for further clinical and genetic follow up to exclude possible tumors and other accompanying disorders. CONCLUSION: We present an easy-to-use selection tool to identify children with suspected IH, which results in the selection of the risk group that may benefit from referral to a pediatrician and a clinical geneticist.

Use of Virtual Rehabilitation to Improve the Symmetry of Body Temperature, Balance, and Functionality of Patients with Stroke Sequelae.

BACKGROUND: Stroke rehabilitation that is based on the patients' needs, experiences, and priorities requires extensive knowledge and skills to capture and integrate the perspectives of the subject. PURPOSE: The objective of this study was to evaluate the acute effect of an occupational therapy protocol associated with virtual reality (VR) on the symmetry of body temperature (BTP), balance, and functionality of patients with stroke sequelae. METHODS: Ten patients (69.84 ± 7.55 years) diagnosed with stroke between 2 and 10 years earlier were evaluated during clinical care sessions integrated with VR games. Associated with games, all patients were stimulated to use both upper and lower limbs and distribute body weight symmetrically, and perceptual stimuli of body-half training, alignment, postural control, and balance were given. The variables of thermography (temperature [°C] and body asymmetry) of the upper and lower limbs, balance (Berg scale), and functionality were analyzed before and after the test. RESULTS: BTP was reduced in the 4 upper and lower limb body regions of interest: the right arm (p = 0.024, Cohen's d = 1.02), previous direct hand (p = 0.034, Cohen's d = 1.22), right back hand (p = 0.003, Cohen's d = 1.85) and Left (p = 0.013, Cohen's d = 0.92), right thigh (p = 0.035, Cohen's d = 1.32), and left thigh (p = 0.047, Cohen's d = 0.92). The mean of the bilateral asymmetry variation of the arm in the anterior position at the pre test was classified according to the level of attention monitoring (which means that the asymmetry rate is above normal), changing its state at the end of the intervention to normal. There was an increase in the functional independence score (p = 0.015, Cohen's d = 0.50) and in the static and dynamic balance function (p = 0.001, Cohen's d = 0.07). CONCLUSION: VR associated with occupational therapeutic planning can amplify and potentiate neurological recovery following stroke.

Multiple tumors due to mosaic genome-wide paternal uniparental disomy.

Mosaic genome-wide paternal uniparental disomy is an infrequently described disorder in which affected individuals have signs and symptoms that may resemble Beckwith-Wiedemann syndrome. In addition, they can develop multiple benign and malignant tumors throughout life. Routine molecular diagnostics may not detect the (characteristic) low level of mosaicism, and the diagnosis is likely to be missed. Genetic counseling and a life-long alertness for the development of tumors is indicated. We describe the long diagnostic process of a patient who already had a tumor at birth and developed multiple tumors in childhood and adulthood. Furthermore, we offer clues to recognize the entity.

Hemihyperplasia/hemihypertrophy in adolescents: prospective international study.

AIM: The reported incidence of isolated hemihyperplasia (IH) has a very wide range (from 1:13,000 to 1:86,000 live births) and further clarification is needed. We hypothesized that a survey of the birth prevalence of IH among newborn infants may underestimate the incidence of IH by overlooking late-onset cases. METHODS: The prospective international multicenter study utilized the two-steps selection tool for an anonymous survey of volunteers of 15-18 years old. The initial step was "three measurements-three questions" screening, or "face-palms-calves survey". The subsequent step was an in-depth assessment of selected cases to exclude localized, lesional and syndrome-related cases as well as body asymmetry within normative range and to select suspected cases of IH. This step included measurements of various anatomical regions and a subsequent questionnaire. The participants that were selected in a risk group were advised to refer to medical institutions for clinical, genetic and instrumental investigation. RESULTS: Out of 6000 of selected participants (male, M 3452, female, F 2548), 229 (3.82%) were selected for detailed investigation and 57 (0.95%) were assigned to the risk group. Only 36 of them were actually referred to medical institutions and in two cases the diagnosis of IH was confirmed. CONCLUSION: Our survey indicated the prevalence of IH at the age of adolescence as approximately 1:3000. While IH is a hereditary genetic disorder, it may not be detected in newborns and infants and the true prevalence of the disease can be estimated if older age children are screened.

Síndrome Rusell Silver. Presentación de caso / Russell-Silver syndrome. Presentation of a case

RESUMEN El síndrome Russell Silver es una enfermedad genética de baja frecuencia, caracterizada por retardo del crecimiento prenatal y postnatal, dismorfias faciales y digitales, así como asimetría corporal. Se presenta una paciente femenina de dos años de edad, remitida a consulta de Genética Clínica, por retardo en el desarrollo pondoestatural psicomotor, dismorfias faciales y asimetría corporal. Se realizño el diagnóstico clínico de esta afección. Es importante establecer un diagnóstico precoz para la estimulación temprana, seguimiento multidisciplinario y se brindó un adecuado asesoramiento genético a los familiares (AU).

ABSTRACT The Russell-Silver syndrome is a low-frequency genetic disease, characterized by a pre-natal growth retardation and postnatal digital and facial dysmorphia, and also body asymmetry. We present a female patient, aged 2 years, who was remitted to the consultation of Clinical Genetics because of a retardation in the psychomotor, height-weight development, facial dysmorphia and body asymmetry. The disease was clinically diagnosed. It is important to arrive to a precocious diagnosis for the early stimulation, multidisciplinary follow-up and adequate genetic advice to the relatives (AU).

Síndrome Rusell Silver. Presentación de caso / Russell-Silver syndrome. Presentation of a case

RESUMEN El síndrome Russell Silver es una enfermedad genética de baja frecuencia, caracterizada por retardo del crecimiento prenatal y postnatal, dismorfias faciales y digitales, así como asimetría corporal. Se presenta una paciente femenina de dos años de edad, remitida a consulta de Genética Clínica, por retardo en el desarrollo pondoestatural psicomotor, dismorfias faciales y asimetría corporal. Se realizño el diagnóstico clínico de esta afección. Es importante establecer un diagnóstico precoz para la estimulación temprana, seguimiento multidisciplinario y se brindó un adecuado asesoramiento genético a los familiares (AU).

ABSTRACT The Russell-Silver syndrome is a low-frequency genetic disease, characterized by a pre-natal growth retardation and postnatal digital and facial dysmorphia, and also body asymmetry. We present a female patient, aged 2 years, who was remitted to the consultation of Clinical Genetics because of a retardation in the psychomotor, height-weight development, facial dysmorphia and body asymmetry. The disease was clinically diagnosed. It is important to arrive to a precocious diagnosis for the early stimulation, multidisciplinary follow-up and adequate genetic advice to the relatives (AU).

Asymmetry of the Vertebral Body and Pedicles in the True Transverse Plane in Adolescent Idiopathic Scoliosis: A CT-Based Study.

STUDY DESIGN: Cross-sectional. OBJECTIVES: To quantify the asymmetry of the vertebral bodies and pedicles in the true transverse plane in adolescent idiopathic scoliosis (AIS) and to compare this with normal anatomy. SUMMARY OF BACKGROUND DATA: There is an ongoing debate about the existence and magnitude of the vertebral body and pedicle asymmetry in AIS and whether this is an expression of a primary growth disturbance, or secondary to asymmetrical loading. METHODS: Vertebral body asymmetry, defined as left-right overlap of the vertebral endplates (ie, 100%: perfect symmetry, 0%: complete asymmetry) was evaluated in the true transverse plane on CT scans of 77 AIS patients and 32 non-scoliotic controls. Additionally, the pedicle width, length, and angle and the length of the ideal screw trajectory were calculated. RESULTS: Scoliotic vertebrae were on average more asymmetric than controls (thoracic: AIS 96.0% vs. controls 96.4%; p = .005, lumbar: 95.8% vs. 97.2%; p < .001) and more pronounced around the thoracic apex (95.8%) than at the end vertebrae (96.3%; p = .031). In the thoracic apex; the concave pedicle was thinner (4.5 vs. 5.4 mm; p < .001) and longer (20.9 vs. 17.9 mm; p < .001), the length of the ideal screw trajectory was longer (43.0 vs. 37.3 mm; p < .001), and the transverse pedicle angle was greater (12.3° vs. 5.7°; p < .001) than the convex one. The axial rotation showed no clear correlation with the asymmetry. CONCLUSIONS: Even in non-scoliotic controls is a degree of vertebral body and pedicle asymmetry, but scoliotic vertebrae showed slightly more asymmetry, mostly around the thoracic apex. In contrast to the existing literature, there is no major asymmetry in the true transverse plane in AIS and no uniform relation between the axial rotation and vertebral asymmetry could be observed in these moderate to severe patients, suggesting that asymmetrical vertebral growth does not initiate rotation, but rather follows it as a secondary phenomenon. LEVEL OF EVIDENCE: Level 4.

Anticipatory and compensatory postural adjustments in conditions of body asymmetry induced by holding an object.

The effect of body asymmetry on anticipatory and compensatory postural adjustments was studied. Ten healthy subjects stood on the force platform and held an object in one hand which induced body asymmetry. Subjects were exposed to external perturbations applied to their shoulders while standing with either normal or narrow base of support. Bilateral electromyographic activity (EMG) of dorsal and ventral trunk and leg muscles and center-of-pressure displacements were recorded. Data was analyzed within the intervals typical for anticipatory (APA) and compensatory postural adjustments. Integrals of EMG activity and co-contraction and reciprocal activation of muscles were calculated and analyzed. Reciprocal activation of muscles on the target side and co-contraction of muscles on the contralateral side were seen when standing in asymmetrical stance and being subjected to external perturbations. Decreased magnitudes of co-contraction and reciprocal activation of muscles were seen in the APA phase while standing asymmetrically with narrow base of support. The findings highlight the importance of investigating the role of body asymmetry in maintaining control of vertical posture. The outcome of the study provides a foundation for future studies focusing on improvement in postural control in individuals with body asymmetry due to unilateral weakness.

The developmental genetics of dextrality and sinistrality in the gastropodLymnaea peregra.

The genetics of body asymmetry inLymnaea peregra follows a maternal mode of inheritance involving a single locus with dextrality being dominant to sinistrality. Maternal inheritance implies that all members of a brood have the same phenotype, however, some broods contain a few individuals of opposite coil. One purpose of this paper is to explain the origin of these anomalous individuals. Genetic analyses of sinistral broods with a few dextral individuals have led to the development of a cross-over model, with the anomalous dextrals originating as a consequence of crossing over either during meiosis or mitosis in the female germ line. The crossover either reconstitutes the dextral gene from previously dissociated parts, or creates a dextral gene by means of a position effect. The probability of a crossover event depends upon the appropriate combination of complementary sinistral chromosomes. Each crossover event has the potential of creating a unique dextral gene. Genetic analyses of dextral broods containing a few sinistral individuals have demonstrated that different dextral genes vary in penetrance.The dextral gene produces a product during oogenesis which influences the pattern of cleavage in the embryo; this cleavage pattern is translated into the appropriate body asymmetry. The other purpose of this paper is to provide an assay for this gene product. Cytoplasm from dextral eggs injected into uncleaved sinistral eggs causes these eggs to cleave in a dextral pattern. Cytoplasm from sinistral eggs has no effect on the cleavage pattern of dextral eggs. While the dextral gene product is made during oogenesis, it does not function in controlling cleavage until just before this process begins.