Musculoskeletal abnormalities in a large international cohort of boys with 49,XXXXY.

49,XXXXY is the rarest X and Y chromosomal variation, with an incidence of 1 in 80,000-100,000 live male births and has been associated with numerous musculoskeletal abnormalities. Data was collected from an international cohort of boys with 49,XXXXY over 10 years. Children were evaluated by a multidisciplinary team consisting of a pediatric orthopedist, a neurogeneticist, a neurodevelopmentalist, and two physical therapists. Increased rates of torticollis (32.4%), hamstring tightness (42%), radioulnar synostosis (67.6%), pes planus (65.2%), and other foot abnormalities (86.9%) were observed. Several anomalies increased with age, specifically hamstring tightness, kyphosis, and scoliosis. The elucidation of the orthopedic profile of this population is necessary in order to provide healthcare providers with current medical information. This research further supports the necessity for the comprehensive multidisciplinary treatment of boys with 49,XXXXY.

Oculo-skeletal dysplasia in five Labrador Retrievers.

OBJECTIVE: To describe the clinical features and diagnostic findings of Labrador Retrievers with oculo-skeletal dysplasia (OSD). ANIMAL STUDIED: Five privately owned dogs. PROCEDURES: Medical records of dogs diagnosed with OSD from 2008 through 2018 were reviewed. Patients were excluded if lacking disease confirmation through genetic testing (Optigen RD/OSD). Information collected included signalment, physical and ophthalmic examination findings, results of ocular ultrasound and electroretinogram, and digital radiographs of forelimbs and pelvis. RESULTS: All five dogs were Labrador Retrievers, confirmed to be homozygote for the OSD mutation. The main physical abnormalities were vision deficits (5 dogs), short-limbed dwarfism (5), carpal valgus (4), and color dilution alopecia (4). The main ophthalmic anomalies were cataracts (10 eyes), vitreous syneresis (10), retinal separation (6), persistent hyperplastic primary vitreous (2), lens coloboma (2), microphakia (2), and persistent tunica vasculosa lentis (1). Ocular ultrasound and electroretinogram confirmed the diagnoses of retinal separations and persistent hyperplastic primary vitreous. Radiographic changes included shortening of ulna and curved radius (5 dogs), elbow incongruity and osteoarthritis (4 dogs), hip dysplasia (3), and coxofemoral osteoarthritis (2). Available follow-up information (2 dogs) showed progression of cataract from incipient to mature in one dog, necessitating cataract surgery, and progression of cataract and lameness in another dog. CONCLUSIONS: The clinical findings of OSD are described in five Labrador Retrievers. DNA testing is critical to diagnose OSD and help eradicate this condition from the breed. Progression of cataracts and osteoarthritis in dogs with OSD warrants yearly monitoring.

Inclusion of joint laxity, recurrent patellar dislocation, and short distal ulnae as a feature of Van Den Ende-Gupta syndrome: a case report.

BACKGROUND: Van Den Ende-Gupta Syndrome (VDEGS) is an extremely rare autosomal recessive syndrome with less than 20 reported families (approximately 40 patients) in the worldwide literature. CASE PRESENTATION: We have assessed one consanguineous Saudi family with typical features of VDEGS. Two siblings were affected with almost identical features; including blepharophimosis, arachnodactyly, flexion contractures of the elbows, camptodactyly, slender ribs, hooked lateral clavicular ends, and bilateral radial head dislocations. Both patients had several unusual features; including joint laxity, flat feet, recurrent patellar dislocations, and bilateral short distal ulnae. Full sequencing of SCARF2 revealed a homozygous mutation c.773G > A (p. Cys258Tyr) in both affected children. The parents (both with no abnormalities) were heterozygous for the same mutation. CONCLUSION: Joint laxity, recurrent patellar dislocations, and short distal ulnae should be included as part of the clinical spectrum of VDEGS.

Deletions of 5' HOXC genes are associated with lower extremity malformations, including clubfoot and vertical talus.

BACKGROUND: Deletions of the HOXC gene cluster result in variable phenotypes in mice, but have been rarely described in humans. OBJECTIVE: To report chromosome 12q13.13 microdeletions ranging from 13 to 175 kb and involving the 5' HOXC genes in four families, segregating congenital lower limb malformations, including clubfoot, vertical talus and hip dysplasia. METHODS: Probands (N=253) with clubfoot or vertical talus were screened for point mutations and copy number variants using multiplexed direct genomic selection, a pooled BAC targeted capture approach. SNP genotyping included 1178 probands with clubfoot or vertical talus and 1775 controls. RESULTS: The microdeletions share a minimal non-coding region overlap upstream of HOXC13, with variable phenotypes depending upon HOXC13, HOXC12 or the HOTAIR lncRNA inclusion. SNP analysis revealed HOXC11 p.Ser191Phe segregating with clubfoot in a small family and enrichment of HOXC12 p.Asn176Lys in patients with clubfoot or vertical talus (rs189468720, p=0.0057, OR=3.8). Defects in limb morphogenesis include shortened and overlapping toes, as well as peroneus muscle hypoplasia. Finally, HOXC and HOXD gene expression is reduced in fibroblasts from a patient with a 5' HOXC deletion, consistent with previous studies demonstrating that dosage of lncRNAs alters expression of HOXD genes in trans. CONCLUSIONS: Because HOXD10 has been implicated in the aetiology of congenital vertical talus, variation in its expression may contribute to the lower limb phenotypes occurring with 5' HOXC microdeletions. Identification of 5' HOXC microdeletions highlights the importance of transcriptional regulators in the aetiology of severe lower limb malformations and will improve their diagnosis and management.

A familial case of trichorhinophalangeal syndrome type I.

Trichorhinophalangeal type I (TRPS I) is a rare autosomal dominant disorder characterized by variable clinical expression of sparse and slow-growing hair, pear-shaped nose, elongated philtrum, and bone deformities, including cone-shaped epiphyses of the phalanges and short stature. We describe three members of a family who consulted us because of slow-growing scalp hair with craniofacial and radiological features typical of TRPS I.

Prenatal diagnosis of isochromosome 20q in a fetus with vertebral anomaly and rocker-bottom feet.

OBJECTIVE: Isochromosome of the long arm of chromosome 20 (i(20q)) is a rare structural abnormality in prenatal diagnosis. Thirty prenatal cases of mosaic i(20q) have been reported, among which only four are associated with fetal malformations. We describe a new prenatal case of i(20q) with fetal malformations. MATERIALS AND METHODS: We also observed a discrepancy between uncultured and cultured amniotic fluid cells by using conventional cytogenetic, fluorescence in situ hybridization and array-SNP analysis. RESULTS: The short arm deletion of chromosome 20 arising from the isochromosome encompassed two candidate genes PAX1 and JAG1 involved in cranio-facial and vertebral development. CONCLUSION: The data would allow establishing a phenotype-genotype correlation. Thus, we proposed to define a recognizable syndrome combining cranio-facial dysmorphism, vertebral bodies' anomalies, feet and cerebral malformations.

The developmental anatomy of pes valgo planus.

Pes planus or flatfoot becomes a medical problem only when symptoms develop. The mere absence of a well-formed medial longitudinal arch does not necessarily imply pathology. Many apparently "flat feet" demonstrate congruent joints, and the extremities function normally. The size and shape, as well as the angles of declination for the talus or astragulers and the calcaneus or os calcis, are most often determined at the moment of fertilization by the genes of the patients. The zygote or fertilized ovum is a first totipotent. Cell division normally occurs as development proceeds, but the embryo is vulnerable to alterations of the cell cycle. Teratogenic substances can induce death or substantial structural modifications to the developing fetus. The post-World War II tragedy of the medical use of the drug thalidomide in pregnant mothers resulting in amelia is testimony as to how the lower extremity can be adversely affected. Early chromosomal aberrations including duplication, deletion, breakage, inversion, translocation, and mosaicism have been shown to be involved in faulty development of the foot, and there is no reason not to implicate pes valgo planus to these events. Intrauterine development apart from the genetic considerations just mentioned place the fetus under additional jeopardy. Even extraembryonic membranes can form strands of tissue that can entangle the delicate developing foot plate, and calcaneovalgus deformities could conceivably be established. The developing embryo and fetus first demonstrate a blastema that forms limb buds on the ventral caudal aspect. Anlage of the scleroblastema and myoblastema of the prospective leg and foot develop in the presence of nerve trunks. Such nerves are related to the lumbosacral plexus and they are thought to exert inductive developmental influences. Interference with any of these events may be implicated in pedal deformities such as pes valgo planus. This is also true of subsequent morphogenetic events involving embryonic rotations, osteogenesis, and myogenesis. Many pedal deformities have congenital basis and it is clear that pes valgo planus is one of them. Post-natal structural changes further accentuate underlying etiologies. For example, the calcaneus normally exhibits a varus position at birth, but this feature diminishes until the cessation of bone growth. The adult talar neck-calcaneal angle is normally about 24 degrees, representing a 6-degrees reduction from that of 30 degrees, which is demonstrated at birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Painful pes planovalgus: an uncommon pediatric orthopedic presentation of Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth (CMT) disease is an inherited progressive neurologic disorder often diagnosed by the characteristic cavovarus feet. In the pediatric population, the presentation is often more variable and age dependent. Pediatric orthopedic surgeons may be referred patients for the evaluation of musculoskeletal symptoms that may be consistent with early CMT, but because of the lack of the surgeon's familiarity, the diagnosis may be delayed or missed. We present three patients with pes planovalgus who were found to have CMT and review the recent literature relevant to the pediatric orthopedic surgeon. The clinical summary is given for three patients who presented to the orthopedic surgery department for lower extremity symptoms and were eventually diagnosed with CMT. A literature search was performed and information valuable for a pediatric orthopedic surgeon to consider is summarized. Foot morphology in most young children with CMT initially is pes planovalgus, with the minority being pes cavovarus. As the child grows, the proportion changes to become nearly entirely cavus or cavovarus, with very few remaining planovalgus or planus. Unexplained regional pain may also be suggestive of CMT. Whereas CMT often presents initially in adolescent or adult patients with cavovarus feet, thin calves, or a high-stepping gait, pediatric presentation is not so consistent. Young children with CMT often have pes planovalgus. There are even some variants of CMT where patients still may present with severe pes planovalgus into late adolescence. We recommend that pediatric orthopedic surgeons consider CMT even in patients who do not have cavus or cavovarus feet, especially in the context of unexplained regional pain of the lower extremities. Patients should be referred to a pediatric neurologist for definitive diagnosis and management, with the orthopedic surgeon remaining involved for specific procedures.

Prevalencia de alteraciones posturales en niños de Arica -Chile: efectos de un programa de mejoramiento de la postura / Prevalence of postural alterations and effects of a program to improve the posture in children from Arica-Chile

Los objetivos de este trabajo fueron calcular el índice de prevalencia de alteraciones posturales en una muestra de 120 alumnos (10,4 por ciento del universo total), de 4 años de edad de la ciudad de Arica y determinar el efecto de un programa de mejoramiento postural. Las alteraciones posturales más frecuentes corresponden a: inclinación de hombros (86 por ciento), escápula alada y escápula descendida (82 por ciento), proyección anterior de hombros (79 por ciento), pie plano (58 por ciento), columna lumbar hiperlordótica (51 por ciento) e inclinación de cabeza (50 por ciento). Posteriormente, se aplicó al grupo experimental un programa de ejercicio muscular y de reeducación postural, por un período de 8 meses. Al final del tratamiento se realizó un análisis post test a todos los sujetos del estudio. Los resultados en el grupo experimental muestran una disminución significativa de los índices iniciales de prevalencia, en todas las alteraciones en estudio. Los diferenciales de recuperación muestran diferencias significativas entre los grupos de estudio, con un 31 por ciento para inclinación de hombros, seguida de hiperlordosis lumbar con un 29 por ciento e inclinación de cabeza con 20 por ciento. La recuperabilidad más baja se observó en pie plano con un 7 por ciento (p≤0,05). El alto porcentaje de alteraciones posturales presentes en niños de 4 años, de la ciudad de Arica, podría ser producto de actitudes viciosas que, a futuro producen una estructuración inadecuada del cuerpo, entonces la aplicación de un programa de ejercitación muscular y de reeducación postural, dirigido por un equipo de Salud multiprofesional disminuirían significativamente estas alteraciones.

At present the educational institutions do not have an adequate system of Health to detect early changes in postural alteration in children. The aim of this study was to determine the most common postural changes in a sample of 120 students (10,4 percent of total universe), of 4 years old from Arica-Chile and to determine the effect of a program to improve the posture. The prevalence of the most frequent postural alterations relate to: inclination of shoulders (86 percent), winged scapula and descend scapula (82 percent), projection front shoulders (79 percent), flat feet (58 percent), lumbar hyperlordosis (51 percent) and inclination of head (50 percent). Subsequently in the experimental group was applied a program of exercise muscle and postural reeducation for a period of 8 months. At the end of treatment was applied a post-test to all children. The results in the experimental group showed a significant decrease in initial prevalence rates in all alterations. The differential recovery shows significant differences among the study groups, with 31 percent for inclination of shoulders, followed by lumbar hyperlordosis (29 percent) and inclination of head (20 percent). The recoverability lowest level was observed in flat feet with 7 percent (p≤0,05).The high percentage of postural disturbances in children aged 4 years in the city of Arica, could be the result of vicious attitudes that in the future produce an improper structuring of the body. Then the implementation of a program of exercise muscles and postural reeducation, led by a multiprofesional health team, decline rates of postural abnormalities present in children.

A syndrome of keratosis palmo-plantaris congenita, pes planus, onychogryphosis, periodontosis, arachnodactyly and a peculiar acro-osteolysis.

A family with a symptom complex of pes planus, onychogryphosis, palmoplantar hyperkeratosis and periodontosis is reported. A detailed pedigree is given and the mode of inheritance is suggested.

Osteoarticular abnormalities and orthopedic complications in children with chromosomal aberrations.

Chromosome abnormalities may result in a great number of osteo-articular anomalies. Little documentation concerning these anomalies is available. The main orthopedic problems encountered in 67 children with chromosomal abnormalities are reported here. Patients should be evaluated at regular intervals in order to detect osteoarticular involvement. Gradual deterioration results in disabling conditions which are difficult to manage. Orthopedic management should be mainly preventive. It's purpose is to delay or to avoid the onset of disabling complications.

Congenital malformation of the feet with low body height. A new syndrome, caused by an autosomal dominant gene.

Among 75 members of a Danish family, 12 were found with a syndrome not previously described. Clinically, the syndrome consists of low body height and rigid flat feet, with weight-bearing pain in the feet. Radiologically, the deformation of the feet is a medial synostosis between the talus and the calcaneus combined with ankle joint dysplasia. The cause of the syndrome is most probably an autosomal dominant gene with complete penetrance. No linkage was found of the gene to 18 marker genes.

The footprint ratio as a predictor of pes planus: a study of indigenous Malawians.

The footprint ratio or arch index is the ratio of the middle third of the toeless footprint to the total toeless footprint area. This ratio was determined in an indigenous Malawian population to classify the foot arch type and the incidence of pes planus. The dynamic footprints of 305 able-bodied subjects, free from foot pain, comprising 139 males and 166 females aged between 13 and 17 years, were studied from randomly selected secondary schools in the city of Blantyre. Males had higher arch index than female, but this was not statistically significant (p > .5). The incidence of pes planus was 242.6/1000 using the arch index method. This incidence was higher when it was compared to other methods. Furthermore, the index was found to be statistically higher in Malawians than Caucasian Americans (p < .001) and Europeans (p < .01) previously studied using similar methods. The study has shown probably for the first time the arch index of an African population, and it shows racial variations between Caucasians and Africans. Also the reliability and reproducibility of the arch index method in determining the incidence of pes planus in a given population has been confirmed.