Combined clinic and home-based therapeutic approach for the treatment of bilateral radial deficiency for a young child with Holt-Oram syndrome: A case report.

BACKGROUND: Holt-Oram syndrome (HOS) is a rare, genetic condition characterized by the combination of congenital heart defect and hypoplasia in one or both upper extremities. Children with HOS commonly present with varied joint and limb involvement including radial longitudinal deficiency impacting hand function. Evidence-based guidelines regarding orthotic wear and therapeutic techniques are lacking. PURPOSE: The aim of this case report was to present the results of a long-term occupational therapy program for a patient with HOS pre and postpollicization. STUDY DESIGN: Case report. METHODS: A 4-month-old patient with bilateral radial longitudinal deficiencies began outpatient occupational therapy for custom orthosis fabrication and treatment which included long term clinic and home-based intervention. Techniques included passive range of motion, orthosis wear, therapeutic taping, and modified constraint induced movement therapy. Longitudinal assessment of musculoskeletal alignment and functional hand use was performed using goniometry for passive and active range of motion, the Assisting Hand Assessment (AHA), and The Thumb Grasp and Pinch Assessment (T-GAP). RESULTS: Improvement in passive and active range of motion was achieved as well as improved activity level function as measured by the AHA and T-GAP postpollicization and intervention. CONCLUSIONS: A combined clinic and home-based therapeutic approach can be effective for children with HOS to improve alignment and function pre and postpollicization to further enhance hand function. Comprehensive, long-term assessment is necessary to fully evaluate and communicate improvement.

Caring for Children With Congenital Upper Extremity Differences.

The purpose of this article is to provide information about the changing landscapes in research, treatment, civil rights' protection, disability awareness, and accepted terminology in the care of children with congenital upper limb differences. This knowledge can guide clinical and nonclinical conversations between patients and their families.

T-Cell Acute Lymphoblastic Leukemia in a Young Adult With Thrombocytopenia-absent Radius Syndrome: A Case Report and Review of the Literature.

Thrombocytopenia-absent radius (TAR) syndrome is a rare inherited bone marrow failure syndrome not generally associated with acute leukemia. The authors report a case of T-cell acute lymphoblastic leukemia in an adult female individual newly diagnosed with TAR syndrome. A 347-kb microdeletion of chromosome 1q21.1 involving the RBM8A gene was detected within a gain of whole chromosome 1. Next-generation sequencing on fibroblasts confirmed germline heterozygous deletion of RBM8A but on the other allele, noncoding low-frequency regulatory single-nucleotide polymorphism of RBM8A (rs139428292; rs201779890) were not found. The tolerance of the treatment was unusual and mostly marked by a slow hematopoietic recovery leading to a 6-month delay at the beginning of the maintenance phase. Only 5 cases of acute leukemia were reported in patients with TAR syndrome in the literature: 4 acute myeloid leukemia and one B-cell acute lymphoblastic leukemia. This is the first report of T-cell acute lymphoid leukemia occurring in the context of TAR syndrome.

Hospital Care and Surgical Treatment of Children With Congenital Upper Limb Defects.

BACKGROUND AND AIMS: To evaluate hospital care of children with congenital upper limb defects. MATERIALS AND METHODS: Three hundred and sixty-two children with an upper limb defect, born 1993-2005, and alive after birth admission were identified in the Finnish Register of Congenital Malformations. The data on hospital care, with focus on operative treatment, were collected from the National Hospital Discharge Register, until 31 December 2009. Mean follow-up was 10.2 years (range: 4-17 years). The results were compared with data on the whole children population (1.1 million) in Finland. RESULTS: Most children (321, 87%) with upper limb defects had hospital admissions: on average, one admission/year (range: 0-36), and they were treated in hospital 5 days/year (range: 0-150), which is 11-fold compared with an average child in Finland. Four surgical procedures/child were done (range: 0-45), including one hand surgical procedure. The most common procedures were orthopedic (513); gastrointestinal (263); ear, nose, and throat (143); dental (118); thoracic (48); and urologic (44). Of the 513 orthopedic procedures, 326 were directed to upper limbs, 107 to the lower limbs, and 10 to the spine. Median operation age was 2 years 7 months. Altogether, 60% of hospital admissions were non-surgical. Leading causes of non-operative hospital admissions were congenital anomalies (32%), gastroenterological problems (20%), respiratory tract conditions (13%), neurological problems (7%), perinatal conditions (5%), and infectious diseases (5%). CONCLUSION: Treatment of children with upper limb defects is teamwork between pediatric and surgical subspecialties. Burden of hospital care is 11-fold as compared with an average child.

A systematic review of the use of psychological assessment tools in congenital upper limb anomaly management.

STUDY DESIGN: This study is a systematic review. INTRODUCTION: Congenital upper limb anomalies (CULAs) are often associated with psychosocial difficulties including negative body image, low self-esteem, and withdrawal from social activities. PURPOSE OF THE STUDY: The purpose of the study was to identify, describe, and evaluate all published psychosocial assessment tools used in the assessment and management of CULAs, to direct the use of these tools in clinical practice, and to identify areas requiring development. METHODS: A systematic search of Medline, EMBASE, Pubmed, and PsychInfo databases was performed. In total, 23 studies were included for analysis. Data extracted included study and population characteristics, psychosocial measures utilized, psychosocial outcomes reported, and the reliability and validity of measures. RESULTS: Seventeen patient-reported measures were identified. The most commonly used tool was a Likert scale (n =7) with satisfaction with appearance and function, the most commonly evaluated outcome (n = 18). Other evaluated domains included quality of life or psychosocial functioning (n = 9), self-image (n = 2), and psychological well-being (n = 5). DISCUSSION AND CONCLUSIONS: There is no well-established, validated assessment tool in regular use to effectively address psychosocial outcomes for children with CULAs. Although the majority of children born with a CULA appear to adjust well, this is by no means the case for all children. There is a need for routine psychosocial evaluation preoperatively and postoperatively with long-term follow-up data to help direct patient-orientated management. A clear understanding of these, and how to measure them, is needed to help for a patient-centred, multidisciplinary, evidence-driven approach to CULA management.

[CHARACTERISTICS AND TRENDS OF CONGENITAL AND ACQUIRED LOWER LIMB DEFICIENCY IN CHILDREN AND ADOLESCENTS AT THE SHEBA MEDICAL CENTER].

INTRODUCTION: Lower limb deficiency in childhood has an impact on acquisition of motor skills. Information regarding the characteristics of this population was examined in several countries but not in Israel. AIMS: To provide demographics, clinical and functional characteristics of children with lower limb deficiency in a pediatric rehabilitation department. METHODS: Children with lower limb deficiency participated in this study. The study variables included demographics, and clinical and functional characteristics. The statistical analysis included calculations of frequency, chi-squared tests and correlations. RESULTS: During the years 1998-2015 fifty-eight children with lower extremity deformity were treated/examined in the department (mean age: 6.46+4.70 years; girls, n=21; congenital deformity, n=23; acquired deformity, n=35). The most common congenital and acquired injury was unilateral leg deformity (31% and 35%, respectively). In congenital injury, multi-limb deformity (including an involvement in the upper limb) is more prevalent than bilateral lower limb deformity (p<0.01). In children with congenital deformity, longitudinal deformity is more prevalent than transverse deformity (p<0.03). Among children with acquired injury, in 40% the etiology was sickness-related and in the rest traumatic. Among the traumatic group, 57% of the injuries were terror-related. More than 50% percent of the children underwent a complex surgical procedure (34% and 22% among congenital and acquired injury, respectively). The ambulation level of the sample was lower than expected. CONCLUSIONS: Children who received treatment due to lower limb deformity presented high variability in their characteristics and low ambulation level. Consequently, it is important to create and manage a register for pediatric lower limb deformity.

Acute myeloid leukemia in a patient with thrombocytopenia with absent radii: A case report and review of the literature.

Thrombocytopenia with absent radii (TAR) syndrome is a rare congenital disorder characterized by low platelet counts of various severity, bilateral absent radii but thumbs are usually present. TAR syndrome is not generally associated with bone marrow failure or malignancy. Janus kinase-2, myeloproliferative leukemia protein, and calreticulin are not mutated in TAR patients. Only four cases of leukemia were reported in TAR patients in the literature: three acute myeloid leukemia (AML) and one acute lymphoblastic leukemia. Of the three cases of AML found in TAR patient, only one was reported in an adult. We report a case of myelodysplastic syndrome progressing to AML with calreticulin driver mutation in an adult male with TAR syndrome who was successfully treated with hematopoietic allogeneic stem cell transplantation.

Radial Longitudinal Deficiency: Recent Developments, Controversies, and an Evidence-Based Guide to Treatment.

Radial longitudinal deficiency (RLD) is the most common congenital longitudinal deficiency at birth and represents a wide spectrum of upper extremity anomalies, from mild thumb hypoplasia to absent radius. Radial dysplasia may be isolated or associated with an array of systemic anomalies that should be familiar to pediatric hand surgeons. The management of RLD has evolved greatly since its inception in the late 19th century, largely due to decades of innovation that followed the thalidomide catastrophe of the 1960s. Yet controversy still exists regarding many aspects of RLD. Traditional treatments of radial dysplasia (ie, centralization) are unfortunately wrought with poor outcomes and high rates of recurrence, leading some authors to recommend alternative techniques for this condition. Reconstruction of the hypoplastic thumb, although less controversial, is just starting to see long-term outcomes. This article reviews the etiology, classification, and treatment options for RLD, highlighting recent developments and outcomes.

Pectus excavatum e assimetrias mamárias: correção com mamoplastia de aumento / Pectus excavatum and breast asymmetry: correction with breast augmentation

Introdução: O pectus excavatum é definido com uma depressão aproximando o esterno e as cartilagens costais à coluna vertebral. Existem diversas teorias em relação à etiologia; a mais aceita consiste no crescimento exagerado das cartilagens costais, causando um deslocamento posterior do esterno e consequente depressão. Dentre as formas de tratamento, encontra-se a correção das assimetrias mamárias utilizando próteses mamárias de silicone em pacientes sem sintomas cardiopulmonares, apenas com queixa estética. Métodos: Foram revisados os registros em prontuários e registros fotográficos de oito casos de pacientes femininas com diagnóstico de pectus excavatum operadas em um hospital privado na região Sul do Brasil, que procuravam o serviço com queixas estéticas locais, e não apresentavam queixas cardiorrespiratórias. Resultados: Seis casos foram submetidos somente à inclusão de prótese mamária. Uma paciente havia colocado prótese havia 15 anos, sendo essa substituída por novo implante, no mesmo plano. Outra paciente já havia realizado cirurgia de correção de pectus descrito por Nuss, 10 anos antes, vindo a consulta com queixa de hipomastia e assimetria. O tipo anestésico preferido foi a anestesia geral, em cinco dos casos. O plano de inclusão de prótese na quase totalidade dos casos foi o subglandular. Somente uma paciente apresentou complicação (seroma). Conclusões: Evidenciamos, na nossa amostra, que a inclusão de prótese mamária em pacientes com pectus excavatum é capaz de trazer resultados estético harmônicos, atenuando e/ou mascarando o defeito torácico, com resultados estéticos satisfatórios para os pacientes.

Introduction: Pectus excavatum is defined as a depression approaching the sternum and costal cartilages to the spine. Several theories explain its etiology, the most accepted of which is the exaggerated growth of the costal cartilages, which causes a posterior displacement of the sternum and consequent depression. The treatment includes correction of breast asymmetries by using silicone breast implants in patients without cardiopulmonary symptoms, only with esthetic complaints. Methods: We reviewed the medical and photographic records of eight female patients diagnosed as having pectus excavatum, who underwent operation at a private hospital in the southern region of Brazil. These women sought consultation for local esthetic complaints and had no cardiorespiratory complaints. Results: Six patients submitted only for breast prosthesis placement. One patient had a prosthesis implanted 15 years before, which was replaced by a new implant in the same plane. Another patient had undergone pectus repair with Nuss surgery 10 years before, and the patient came to the hospital with a complaint of hypomasty and asymmetry. The preferred anesthesia was general anesthesia in five of the cases. The prosthesis inclusion plane in almost all the cases was subglandular. Only one patient had a complication (seroma). Conclusions: In our sample, the placement of breast prostheses in the patients with pectus excavatum brought harmonic esthetic results, attenuating and/or masking the chest defect, with satisfactory esthetic results for the patients.

Neonatal manifestations of inherited bone marrow failure syndromes.

The inherited bone marrow failure syndromes (IBMFS) are a rare yet clinically important cause of neonatal hematological and non-hematological manifestations. Many of these syndromes, such as Fanconi anemia, dyskeratosis congenita and Diamond-Blackfan anemia, confer risks of multiple medical complications later in life, including an increased risk of cancer. Some IBMFS may present with cytopenias in the neonatal period whereas others may present only with congenital physical abnormalities and progress to pancytopenia later in life. A thorough family history and detailed physical examination are integral to the work-up of any neonate in whom there is a high index of suspicion for an IBMFS. Correct detection and diagnosis of these disorders is important for appropriate long-term medical surveillance and counseling not only for the patient but also for appropriate genetic counselling of their families regarding recurrence risks in future children and generations.

MicroRNA 19a replacement partially rescues fin and cardiac defects in zebrafish model of Holt Oram syndrome.

Holt-Oram Syndrome (HOS) is an autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene, a transcription factor capable of regulating hundreds of cardiac-specific genes through complex transcriptional networks. Here we show that, in zebrafish, modulation of a single miRNA is sufficient to rescue the morphogenetic defects generated by HOS. The analysis of miRNA-seq profiling revealed a decreased expression of miR-19a in Tbx5-depleted zebrafish embryos compared to the wild type. We revealed that the transcription of the miR-17-92 cluster, which harbors miR-19a, is induced by Tbx5 and that a defined dosage of miR-19a is essential for the correct development of the heart. Importantly, we highlighted that miR-19a replacement is able to rescue cardiac and pectoral fin defects and to increase the viability of HOS zebrafish embryos. We further observed that miR-19a replacement shifts the global gene expression profile of HOS-like zebrafish embryos towards the wild type condition, confirming the ability of miR-19a to rescue the Tbx5 phenotype. In conclusion our data demonstrate the importance of Tbx5/miR-19a regulatory circuit in heart development and provide a proof of principle that morphogenetic defects associated with HOS can be rescued by transient miRNA modulation.

Inherited bone marrow failure syndromes in adolescents and young adults.

The inherited bone marrow failure syndromes are a diverse group of genetic diseases associated with inadequate production of one or more blood cell lineages. Examples include Fanconi anemia, dyskeratosis congenita, Diamond-Blackfan anemia, thrombocytopenia absent radii syndrome, severe congenital neutropenia, and Shwachman-Diamond syndrome. The management of these disorders was once the exclusive domain of pediatric subspecialists, but increasingly physicians who care for adults are being called upon to diagnose or treat these conditions. Through a series of patient vignettes, we highlight the clinical manifestations of inherited bone marrow failure syndromes in adolescents and young adults. The diagnostic and therapeutic challenges posed by these diseases are discussed.

Severity grading in radial dysplasia.

A functional scoring method to grade the usefulness and quality of the upper limbs in congenital radial dysplasia is presented. It is based on the author's examinations of 44 arms with congenital deficiency of the radius. The hand (H), wrist (W) and proximal parts (P) of the extremity are each scored from 0 to 10 points for severity. The scoring is expressed similarly to the TNM (tumour, nodes, metastasis) tumour classification, for example as H5W4P2. The maximum severity index is 30 points. A severity grade of mild is between 1 and 8 points, moderate between 9 and 16 points and severe 17 points and over. In the author's series, the grades were mild in eight, moderate in 21 and severe in 15 cases. The functional severity grading should allow better comparison of radially deficient limbs and the results of treatment between groups of patients.

Disruption of the radial/ulnar axis:congenital longitudinal deficiencies.

Radial, ulnar, and central deficiencies represent a spectrum of abnormalities in the development of the upper limb. Radial longitudinal deficiency is often associated with abnormalities in other organ systems, such as cardiac and renal, and so requires a comprehensive medical evaluation. On the other hand, ulnar longitudinal deficiency tends to be associated only with other musculoskeletal abnormalities. In all of these conditions, there is a high incidence of ipsilateral thumb abnormalities. Given the importance of the thumb in overall hand function, abnormalities of the thumb often guide treatment for these conditions. Surgical treatment of the wrist and forearm in radial longitudinal deficiency is controversial, as will be outlined in this review.

Inherited thrombocytopenias: an approach to diagnosis and management.

Inherited thrombocytopenias vary in their presentation, associated features, and molecular etiologies. An accurate diagnosis is important to provide appropriate therapy as well as counseling for the individual and their family members. As the genetic basis of more disorders is understood, it will be possible to diagnose a greater fraction of patients as well as learn more about the process of megakaryopoiesis and platelet production.