461 results match your criteria Holt-Oram Syndrome


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.

J Hand Ther 2021 Mar 6. Epub 2021 Mar 6.

NYU Langone Health Rusk Rehabilitation, New York, NY, USA. Electronic address:

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. Read More

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TBX3 and TBX5 duplication: A family with an atypical overlapping Holt-Oram/Ulnar-Mammary syndrome phenotype.

Eur J Med Genet 2021 Apr 27;64(7):104213. Epub 2021 Apr 27.

Department of Clinical Genetics, Guy's Hospital, London, UK. Electronic address:

Holt-Oram syndrome (HOS) is a rare, autosomal dominant heart-hand syndrome caused by mutations in the TBX5 gene. A wide spectrum of TBX5 mutations have been reported previously, most resulting in a null allele leading to haploinsufficiency. TBX5 gene duplications have been previously reported in association with typical and atypical HOS phenotypes. Read More

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Functional analysis of two novel TBX5 variants present in individuals with Holt-Oram syndrome with different clinical manifestations.

Mol Genet Genomics 2021 Apr 17. Epub 2021 Apr 17.

Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal.

Holt-Oram syndrome (HOS) is a rare disorder characterized by cardiac and upper-limb defects. Pathogenic variants in TBX5-a gene encoding a transcription factor important for heart and skeletal development-are the only known cause of HOS. Here, we present the identification and functional analysis of two novel TBX5 pathogenic variants found in two individuals with HOS presenting distinct phenotypes. Read More

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Generation of a TBX5 homozygous knockout embryonic stem cell line (WAe009-A-45) by CRISPR/Cas9 genome editing.

Stem Cell Res 2021 Mar 6;51:102156. Epub 2021 Jan 6.

Anzhen Hospital, Capital Medical University, Beijing 100029, China. Electronic address:

Holt-Oram syndrome (HOS), which is caused by genetic changes in the TBX5 gene, affects the hands and heart. HOS patients have heart defects, including atrial septal defects (ASD), ventricular septal defects (VSD) and heart conduction disease. Here, we generated a homozygous TBX5 knockout human embryonic stem cell (hESC) line (TBX5-KO) using a CRISPR/Cas9 system. Read More

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Micromelic upper limbs and cardiac defect: A fetal case of Holt-Oram syndrome identified in the first trimester.

Eur J Obstet Gynecol Reprod Biol 2021 Mar 19;258:471-473. Epub 2021 Jan 19.

Prenatal Diagnostic Center, Guangzhou Women and Children's Medical Center, Guangzhou, China. Electronic address:

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A novel TBX5 mutation predisposes to familial cardiac septal defects and atrial fibrillation as well as bicuspid aortic valve.

Genet Mol Biol 2020 13;43(4):e20200142. Epub 2020 Nov 13.

Fudan University, Department of Cardiology, Shanghai Fifth People's Hospital, Shanghai, China.

TBX5 has been linked to Holt-Oram syndrome, with congenital heart defect (CHD) and atrial fibrillation (AF) being two major cardiac phenotypes. However, the prevalence of a TBX5 variation in patients with CHD and AF remains obscure. In this research, by sequencing analysis of TBX5 in 178 index patients with both CHD and AF, a novel heterozygous variation, NM_000192. Read More

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November 2020

Heart-hand Syndrome.

Intern Med 2020 Dec 7. Epub 2020 Dec 7.

Department of Cardiovascular Medicine, Chiba University Graduate school of Medicine, Japan.

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December 2020

Clinical and epidemiological features of heart-hand syndrome, an updated analysis in China.

BMC Musculoskelet Disord 2020 Nov 25;21(1):777. Epub 2020 Nov 25.

Department of Hand Surgery, Beijing Ji Shui Tan Hospital, Xin jie kou dong jie 31, Xi Cheng Qu, Beijing, 100035, China.

Background: The purpose of this study was to prospectively recruit patients treated with limb malformation and to explore the prevalence and the clinical and epidemiological features of Heart-Hand Syndrome (HHS) in China.

Methods: The consecutive patients treated for congenital upper limb malformation in Beijing Ji Shui Tan Hospital from October 1st, 2016 to October 1st, 2019 were prospectively recruited. We reviewed the patients' medical records and identified patients with abnormal electrocardiogram (ECG) and/or abnormal ultrasonic cardiogram as well as their basic demographic and clinical characteristics. Read More

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November 2020

Transcriptional regulation of human T-box 5 gene (TBX5) by bone- and cardiac-related transcription factors.

Gene 2021 Feb 19;768:145322. Epub 2020 Nov 19.

Centre of Marine Sciences (CCMAR), University of Algarve, Faro, Portugal; Faculty of Medicine and Biomedical Sciences, University of Algarve, Faro, Portugal; Algarve Biomedical Centre (ABC) University of Algarve, Faro, Portugal; Centre for Biomedical Research (CBMR), University of Algarve, Faro, Portugal. Electronic address:

T-box 5 (TBX5) protein belongs to the T-box family whose members play a crucial role in cell-type specification, morphogenesis and organogenesis. TBX5 is a transcription factor important for cardiac development and upper limbs formation and its haploinsufficiency causes Holt-Oram syndrome (HOS). An increase in TBX5 dosage also leads to HOS, suggesting that TBX5 is a dose-sensitive transcription factor that needs to be tightly regulated but the molecular mechanisms involved remain unclear. Read More

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February 2021

Association of Radial Longitudinal Deficiency and Thumb Hypoplasia: An Update Using the CoULD Registry.

J Bone Joint Surg Am 2020 Oct;102(20):1815-1822

Children's Hospital Boston, Boston, Massachusetts.

Background: Deficiency of the radial aspect of the forearm and hand is the most common congenital longitudinal deficiency of the upper limb. Radial longitudinal deficiency is associated with several named syndromes. The purpose of the present study was to explore patterns of radial longitudinal deficiency and thumb hypoplasia in syndromes and to examine the severity of these differences across various syndromes. Read More

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October 2020

Steroid-associated bradycardia in a newly diagnosed B precursor acute lymphoblastic leukemia patient with Holt-Oram syndrome.

Ann Pediatr Cardiol 2020 Jul-Sep;13(3):241-243. Epub 2020 Jun 2.

Department of Pediatrics, Rush University Medical Center, Chicago, IL, USA.

Holt-Oram syndrome (HOS) (OMIM#142900) is a rare condition with upper extremity malformations as well as structural and conduction cardiac anomalies. There are sparse reports in the literature documenting malignancy in association with HOS. We report a pediatric patient clinically diagnosed with HOS (missing thumbs bilaterally, atrial septal defect, ventricular septal defect, and first-degree heart block), who also developed B precursor acute lymphoblastic leukemia. Read More

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Congenital superior oblique palsy in a patient with Holt-Oram syndrome.

Neurol Sci 2021 01 24;42(1):373-375. Epub 2020 Jul 24.

Department of Ophthalmology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, South Korea.

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January 2021

Familial dilated cardiomyopathy associated with pathogenic TBX5 variants: Expanding the cardiac phenotype associated with Holt-Oram syndrome.

Am J Med Genet A 2020 07 25;182(7):1725-1734. Epub 2020 May 25.

West of Scotland Clinical Genetics Service, Queen Elizabeth University Hospital, Glasgow, UK.

Holt-Oram syndrome (HOS) is a rare, autosomal dominant disorder caused by heterozygous pathogenic variants in cardiac T-box transcription factor, TBX5. Classically, it is associated with upper limb malformations and variable cardiac abnormalities. Limb manifestations are considered to be invariably present, ranging in severity from limitation in movement, to triphalangeal thumbs, absent thumbs, shortened forearms, or phocomelia. Read More

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Individual Limb Muscle Bundles Are Formed through Progressive Steps Orchestrated by Adjacent Connective Tissue Cells during Primary Myogenesis.

Cell Rep 2020 03;30(10):3552-3565.e6

Randall Centre for Cell and Molecular Biophysics, King's College London, Guy's Campus, London SE1 1UL, UK. Electronic address:

Although the factors regulating muscle cell differentiation are well described, we know very little about how differentiating muscle fibers are organized into individual muscle tissue bundles. Disruption of these processes leads to muscle hypoplasia or dysplasia, and replicating these events is vital in tissue engineering approaches. We describe the progressive cellular events that orchestrate the formation of individual limb muscle bundles and directly demonstrate the role of the connective tissue cells that surround muscle precursors in controlling these events. Read More

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Asymptomatic phaeochromocytoma in a patient with Holt-Oram syndrome: a case report.

Eur Heart J Case Rep 2019 Dec 9;3(4):1-5. Epub 2019 Nov 9.

National University Health System, 5 Lower Kent Ridge Road, Singapore 119074, Singapore.

Background: Holt-Oram syndrome (HOS) is a rare congenital disease that affects the heart and upper limbs. Phaeochromocytoma, a catecholamine-secreting tumour, is a rare neuroendocrine disorder. We present an interesting case presentation of these two rare disorders in a patient who was asymptomatic for phaeochromocytoma. Read More

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December 2019

Growing up with a rare genetic disease: an interpretative phenomenological analysis of living with Holt-Oram syndrome.

Disabil Rehabil 2019 Dec 1:1-8. Epub 2019 Dec 1.

Center of Clinical Psychology, Psychopathology and Psychosomatic Research, Université Libre de Bruxelles, Bruxelles, Belgique.

Holt-Oram syndrome (HOS) is a rare genetic disease characterized by variable radial upper limb and cardiac defects. The aim of this research was to shed light on people's subjective perceptions of their diseases, how these perceptions provide meaning, and the consequences the syndrome can have in daily life and across all life stages. Semistructured interviews with ten participants diagnosed with HOS were conducted in France and analyzed using interpretative phenomenological analysis. Read More

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December 2019

HDAC4 and 5 repression of TBX5 is relieved by protein kinase D1.

Sci Rep 2019 11 29;9(1):17992. Epub 2019 Nov 29.

School of Life Sciences, Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, UK.

TBX5 is a T-box family transcription factor that regulates heart and forelimb development in vertebrates and functional deficiencies in this protein result in Holt-Oram syndrome. Recently, we have shown that acetylation of TBX5 potentiates its activity and is important for heart and limb development. Here we report that class II histone deacetylases HDAC4 and HDAC5 associate with TBX5 and repress its role in cardiac gene transcription. Read More

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November 2019

miR-182-5p is an evolutionarily conserved Tbx5 effector that impacts cardiac development and electrical activity in zebrafish.

Cell Mol Life Sci 2020 Aug 4;77(16):3215-3229. Epub 2019 Nov 4.

Institute of Clinical Physiology, National Research Council, IFC via Moruzzi 1, 56124, Pisa, Italy.

To dissect the TBX5 regulatory circuit, we focused on microRNAs (miRNAs) that collectively contribute to make TBX5 a pivotal cardiac regulator. We profiled miRNAs in hearts isolated from wild-type, CRE, Tbx5and Tbx5 mice using a Next Generation Sequencing (NGS) approach. TBX5 deficiency in cardiomyocytes increased the expression of the miR-183 cluster family that is controlled by Kruppel-like factor 4, a transcription factor repressed by TBX5. Read More

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Holt-Oram Syndrome: Hands are the Clue to the Diagnosis.

Int J Appl Basic Med Res 2019 Oct-Dec;9(4):248-250. Epub 2019 Oct 11.

Department of Cardiology, Advanced Cardiac Centre, PGIMER, Chandigarh, India.

Holt-Oram syndrome or heart-hand syndrome consists of phenotypic and genotypic abnormalities. It is characterized by abnormalities of upper limbs and congenital cardiac defects. It is an autosomal dominant disorder due to a mutation in TBX5 gene located on chromosome 12, but sporadic cases have also been reported. Read More

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October 2019

The role of ESCO2, SALL4 and TBX5 genes in the susceptibility to thalidomide teratogenesis.

Sci Rep 2019 08 6;9(1):11413. Epub 2019 Aug 6.

Programa de Pós-Graduação em Genética e Biologia Molecular, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

Thalidomide is widely used for several diseases; however, it causes malformations in embryos exposed during pregnancy. The complete understanding of the mechanisms by which thalidomide affects the embryo development has not yet been obtained. The phenotypic similarity makes TE a phenocopy of syndromes caused by mutations in ESCO2, SALL4 and TBX5 genes. Read More

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Tbx5 inhibits hedgehog signaling in determination of digit identity.

Hum Mol Genet 2020 06;29(9):1405-1416

Department of Biomedical Sciences, University of North Dakota, Grand Forks, ND 58202, USA.

Dominant TBX5 mutation causes Holt-Oram syndrome (HOS), which is characterized by limb defects in humans, but the underlying mechanistic basis is unclear. We used a mouse model with Tbx5 conditional knockdown in Hh-receiving cells (marked by Gli1+) during E8 to E10.5, a previously established model to study atrial septum defects, which displayed polydactyly or hypodactyly. Read More

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Novel compound heterozygous TBX5 variants may induce hypoplastic left heart syndrome.

Pediatr Int 2019 Jun 18;61(6):607-609. Epub 2019 Jun 18.

Department of Pediatrics, University of Toyama, Toyama, Japan.

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Quantitative anatomy of the primary ossification center of the radial shaft in human fetuses.

Surg Radiol Anat 2019 Aug 2;41(8):901-909. Epub 2019 May 2.

Department of Otolaryngology and Oncology, The Ludwik Rydygier Collegium Medicum in Bydgoszcz, The Nicolaus Copernicus University in Toruń, Toruń, Poland.

Purpose: The medical literature still lacks studies on the size of the radial shaft primary ossification center, thus preventing us from potentially relevant data in diagnosing skeletal dysplasias, i.e., TAR syndrome, VATER syndrome, Holt-Oram syndrome, Fanconi anemia and Edwards syndrome, frequently characterized by disrupted or retarded fetal growth. Read More

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Possible Holt-Oram Syndrome: Missed Prenatal Diagnosis and Sub-Optimal Management in a Poor-Resourced Hospital

Balkan Med J 2019 05 15;36(3):192-193. Epub 2019 Mar 15.

Department of Emergency Medicine, Medway NHS Foundation Trust, Kent, United Kingdom

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Reconstruction of A Type IIIB Hypoplastic Thumb with A Huber Opposition Transfer in A Five-Year-Old Girl: Redefining Surgical Treatment.

World J Plast Surg 2019 Jan;8(1):97-105

Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Thumb hypoplasia, a congenital deficiency of bony and soft tissue of thumb, is often associated with systemic syndromes like Holt-Oram syndrome, and is the second most common thumb anomaly after duplicated thumb. It has traditionally been classified into six categories, which help guide treatment including reconstruction versus pollicization (transfer of the index finger to thumb). Amputation of the thumb and pollicization is the traditional treatment for a IIIB hypoplastic thumb. Read More

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January 2019

Modeling human point mutation diseases in with a modified CRISPR/Cas9 system.

FASEB J 2019 06 7;33(6):6962-6968. Epub 2019 Mar 7.

Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research and.

Precise single-base editing in would greatly expand the utility of this true diploid frog for modeling human genetic diseases caused by point mutations. Here, we report the efficient conversion of C-to-T or G-to-A in using the rat apolipoprotein B mRNA editing enzyme catalytic subunit 1-XTEN-clustered regularly interspaced short palindromic repeat-associated protein 9 (Cas9) nickase-uracil DNA glycosylase inhibitor-nuclear localization sequence base editor [base editor 3 (BE3)]. Coinjection of guide RNA and the Cas9 mutant complex mRNA into 1-cell stage embryos caused precise C-to-T or G-to-A substitution in 14 out of 19 tested sites with efficiencies of 5-75%, which allowed for easy establishment of stable lines. Read More

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Fetal akinesia deformation sequence, arthrogryposis multiplex congenita, and bilateral clubfeet: Is motor assessment of additional value for in utero diagnosis? A 10-year cohort study.

Prenat Diagn 2019 02 7;39(3):219-231. Epub 2019 Feb 7.

Department of Obstetrics and Gynaecology, Amsterdam Movement Sciences, Amsterdam University Medical Centre, VUmc, Amsterdam, the Netherlands.

Objective: The diagnosis of fetal akinesia deformation sequence (FADS) is a challenge. Motor assessment is of additional value to advanced ultrasound examinations (AUE) for in utero FADS diagnosis before 24 weeks of gestation.

Methods: All consecutive fetuses with greater than or equal to two contractures on the 20 week structural anomaly scan (2007-2016) were included. Read More

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February 2019