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Craig T. Basson - One of the best experts on this subject based on the ideXlab platform.

  • Atrial Fibrillation and Other Clinical Manifestations of Altered TBX5 Dosage in Typical Holt–Oram Syndrome
    Circulation research, 2008
    Co-Authors: Deborah A. Mcdermott, Cathy J. Hatcher, Craig T. Basson
    Abstract:

    To the editor: We were pleased to read the recent study in Circulation Research by Postma et al1 that describes an activation mutation in TBX5 that causes Holt–Oram Syndrome. These exciting findings validate prior studies (reviewed elsewhere2) showing that cytogenetic abnormalities that produce TBX5 duplication (and presumed TBX5 overexpression) result in phenotypes that include Holt–Oram Syndrome associated abnormalities. Moreover, we3,4 and others5 have previously demonstrated in experimental models that cell biological consequences of diminished and augmented Tbx5 expression are similar. In aggregate, these prior findings and the current data support a model6 in which Tbx5 dosage must …

  • atrial fibrillation and other clinical manifestations of altered tbx5 dosage in typical Holt Oram Syndrome
    Circulation Research, 2008
    Co-Authors: Deborah A. Mcdermott, Cathy J. Hatcher, Craig T. Basson
    Abstract:

    To the editor: We were pleased to read the recent study in Circulation Research by Postma et al1 that describes an activation mutation in TBX5 that causes Holt–Oram Syndrome. These exciting findings validate prior studies (reviewed elsewhere2) showing that cytogenetic abnormalities that produce TBX5 duplication (and presumed TBX5 overexpression) result in phenotypes that include Holt–Oram Syndrome associated abnormalities. Moreover, we3,4 and others5 have previously demonstrated in experimental models that cell biological consequences of diminished and augmented Tbx5 expression are similar. In aggregate, these prior findings and the current data support a model6 in which Tbx5 dosage must …

  • Holt-Oram Syndrome vs heart-hand Syndrome.
    Circulation, 2000
    Co-Authors: Craig T. Basson
    Abstract:

    To the Editor: In a recent article, Brockhoff et al1 provide an elegant example of a patient affected by a heart-hand Syndrome. Their findings also highlight the importance of modern cardiovascular genetics in clinical diagnosis. Although the patient presented certainly has both a cardiac septation defect and an upper limb deformity, recent DNA-based studies have demonstrated that the hand abnormalities shown would actually make a diagnosis of Holt-Oram Syndrome unlikely. Heart-hand Syndromes are a broad category of disease, of which Holt-Oram Syndrome is the most common form. Other heart-hand Syndromes (reviewed in Reference 2) include Tabatznik’s …

  • mutations in human cause limb and cardiac malformation in Holt Oram Syndrome
    Nature Genetics, 1997
    Co-Authors: Craig T. Basson, Thomas A. Traill, D R Bachinsky, R C Lin, Tatjana Levi, Jacob A Elkins, Johanna Soults, David Grayzel, Elena Kroumpouzou, Janine M Leblancstraceski
    Abstract:

    Holt-Oram Syndrome is characterized by upper limb malformations and cardiac septation defects. Here, we demonstrate that mutations in the human TBX5 gene underlie this disorder. TBX5 was cloned from the disease locus on human chromosome 12q24.1 and identified as a member of the T-box transcription factor family. A nonsense mutation in TBX5 causes Holt-Oram Syndrome in affected members of one family; a TBX5 missense mutation was identified in affected members of another. We conclude that TBX5 is critical for limb and heart development and suggest that haploinsufficiency of TBX5 causes Holt-Oram Syndrome.

  • mutations in human tbx5 corrected cause limb and cardiac malformation in Holt Oram Syndrome
    Nature Genetics, 1997
    Co-Authors: Craig T. Basson, Thomas A. Traill, D R Bachinsky, R C Lin, Tatjana Levi, Jacob A Elkins, Johanna Soults, David Grayzel, Elena Kroumpouzou, Janine M Leblancstraceski
    Abstract:

    Holt-Oram Syndrome is characterized by upper limb malformations and cardiac septation defects. Here, we demonstrate that mutations in the human TBX5 gene underlie this disorder. TBX5 was cloned from the disease locus on human chromosome 12q24.1 and identified as a member of the T-box transcription factor family. A nonsense mutation in TBX5 causes Holt-Oram Syndrome in affected members of one family; a TBX5 missense mutation was identified in affected members of another. We conclude that TBX5 is critical for limb and heart development and suggest that haploinsufficiency of TBX5 causes Holt-Oram Syndrome.

Tsung O. Cheng - One of the best experts on this subject based on the ideXlab platform.

  • Persistent left superior vena cava in Holt-Oram Syndrome.
    International journal of cardiology, 2000
    Co-Authors: Tsung O. Cheng
    Abstract:

    I read with interest the recent case report by where cardiac catheterization is routinely performed, Kranidis et al. of Holt-Oram Syndrome associated its incidence will be comparatively much higher. The with a persistent left superior vena cava [1]. The incidence of associated intracardiac lesion has been authors claimed that their patient was the only case noted to be relatively high, the most frequent being that has been reported so far where the only coexistatrial septal defect [3,4]. Since atrial septal defect is ing cardiovascular anomaly was a persistent left the commonest congenital heart defect in Holt-Oram superior vena cava. Syndrome [2–4], the finding of a persistent left Holt-Oram Syndrome is an autosomal dominant superior vena cava in the proband is understandable. hereditary disorder characterized by congenital carIn the patient with Holt-Oram Syndrome reported diovascular malformations and skeletal anomalies of in 1987 by this author [3], the persistent left superior the upper limb [2]. The association of a persistent left vena cava was associated with an atrial septal defect. superior vena cava with the Holt-Oram Syndrome was Persistent left superior vena cava as an isolated first recognized in a 15-year-old female patient by congenital cardiovascular anomaly in Holt-Oram this author in 1963. The case was later reported in Syndrome was later reported in 1994 by Basson et al. 1987 [3] along with publication of an illustration in 1 of their 37 patients [5]. showing the typical X-ray appearance of the course of the cardiac catheter advanced up the inferior vena cava and into the persistent left superior vena cava References from the right atrium via the coronary sinus. Persistence of the left superior vena cava, which is due [1] Kranidis A, Filippatos G, Karvounis H. A case of Holt-Oram to failure of the left anterior cardinal vein to become Syndrome (heart-hand Syndrome). Int J Cardiol 2000;73:95–6. obliterated during fetal life, as an isolated anomaly is [2] Sun Q-B, Zhang K-Z, Cheng TO. Holt-Oram Syndrome with high myopia. A hitherto unreported association in a Chinese patient. Am a benign condition and of no hemodynamic conseJ Med 1987;82:326–8. quence. The actual incidence is not known and may [3] Cheng TO. Holt-Oram Syndrome in a Puerto Rican family – case vary considerably from one institution to another, reports. Angiology 1987;38:896–902. [4] Zhang K-Z, Sun Q-B, Cheng TO. Holt-Oram Syndrome in China: A depending on the case material studied and the collective review of 18 cases. Am Heart J 1986;111:572–7. method of investigation. If based on necropsy find[5] Basson CT, Cowley GS, Solomon SD et al. The clinical and genetic ings in a general hospital, it will be understandably spectrum of the Holt-Oram Syndrome (heart-hand Syndrome). N low; if based on the findings in a cardiac center Engl J Med 1994;330:885–91.

Athanassios Kranidis - One of the best experts on this subject based on the ideXlab platform.

  • Persistent left superior vena cava in Holt-Oram Syndrome
    International Journal of Cardiology, 2000
    Co-Authors: Gerasimos Filippatos, Athanassios Kranidis
    Abstract:

    We thank Dr Cheng for his comments on our with a cycle length of 545 ms caused a 2:1 distal article [1]. The Holt–Oram Syndrome is characterized block. These abnormalities have been described in by skeletal abnormalities and congenital cardiac patients with Holt–Oram Syndrome. However, and in defects. In a recent article, Basson et al. [2] reported patients with persistent left superior vena cava, it has concordance of Holt–Oram phenotypes with specific been described as sinus node disease and disturbances mutations of the TBX5 gene. Defects predicted to of atrioventricular conduction, as in our case [5,6]. create null alleles caused composite cardiac defects These conduction disturbances have been attributed and severe skeletal malformations. In contrast, misto a probable compression of the atrioventricular ense mutations caused (a) phenotypes with severe conduction system by the enlarged coronary sinus cardiac abnormalities and minor skeletal malforma[7]. tions or (b) phenotypes with extensive upper limb From the existing data we cannot conclude if the malformations but less significant cardiac defects. existence of PLSVC in our patient with Holt–Oram Thus, involvement of heart or limb occurs as the Syndrome is an incidental finding, but it was the only consequence of a specific mutation of a gene. cardiac abnormality. In both cases with Holt–Oram Syndrome and Another point that should be taken into considerapersistent left superior vena cava (PLSVC), described tion in patients with PLSVC, especially if upper limb by Dr Cheng [3,4], another cardiac ‘defect’ was also abnormalities coexist, is that difficulties may arise present (atrial septal defect and increased right venduring the implantation of a permanent pacemaker. In tricular trabeculations, respectively). the case described, we confirmed the difficulties in In the patient with Holt–Oram Syndrome, we have introducing the pacing lead via the persistent left described PLSVC was the only cardiac defect [1]. superior vena cava and in fixating the electrode PLSVC is the most common congenital anomaly of because of its abnormal route through the PLSVC the venous system and there is the possibility that in before arriving in the right ventricle. the described patient, PLSVC was an incidental The need for an active fixation lead in pacing finding in a patient with a mutation that causes only patients with a persistent left superior vena cava has skeletal anomalies. been stressed in the literature [6]. What has not been However, our patient had also history of syncope described is the extreme difficulty involved in removand abnormalities in the conduction system. The ing the pacing lead through this anomalous vessel, electrophysiological study showed abnormal insuch as we encountered in our case. This was traventricular conduction and rapid right atrial pacing probably due to the existence of a valve in the PLSVC, or to stenosis at the point where it drained into the coronary sinus. The difficulties in removing *Corresponding author. Tel.: 130-1-8048-427; fax: 131-1-804-8427. E-mail address: geros@compulink.gr (G. Filippatos). the conventional lead had a negative effect on the

Gerasimos Filippatos - One of the best experts on this subject based on the ideXlab platform.

  • Persistent left superior vena cava in Holt-Oram Syndrome
    International Journal of Cardiology, 2000
    Co-Authors: Gerasimos Filippatos, Athanassios Kranidis
    Abstract:

    We thank Dr Cheng for his comments on our with a cycle length of 545 ms caused a 2:1 distal article [1]. The Holt–Oram Syndrome is characterized block. These abnormalities have been described in by skeletal abnormalities and congenital cardiac patients with Holt–Oram Syndrome. However, and in defects. In a recent article, Basson et al. [2] reported patients with persistent left superior vena cava, it has concordance of Holt–Oram phenotypes with specific been described as sinus node disease and disturbances mutations of the TBX5 gene. Defects predicted to of atrioventricular conduction, as in our case [5,6]. create null alleles caused composite cardiac defects These conduction disturbances have been attributed and severe skeletal malformations. In contrast, misto a probable compression of the atrioventricular ense mutations caused (a) phenotypes with severe conduction system by the enlarged coronary sinus cardiac abnormalities and minor skeletal malforma[7]. tions or (b) phenotypes with extensive upper limb From the existing data we cannot conclude if the malformations but less significant cardiac defects. existence of PLSVC in our patient with Holt–Oram Thus, involvement of heart or limb occurs as the Syndrome is an incidental finding, but it was the only consequence of a specific mutation of a gene. cardiac abnormality. In both cases with Holt–Oram Syndrome and Another point that should be taken into considerapersistent left superior vena cava (PLSVC), described tion in patients with PLSVC, especially if upper limb by Dr Cheng [3,4], another cardiac ‘defect’ was also abnormalities coexist, is that difficulties may arise present (atrial septal defect and increased right venduring the implantation of a permanent pacemaker. In tricular trabeculations, respectively). the case described, we confirmed the difficulties in In the patient with Holt–Oram Syndrome, we have introducing the pacing lead via the persistent left described PLSVC was the only cardiac defect [1]. superior vena cava and in fixating the electrode PLSVC is the most common congenital anomaly of because of its abnormal route through the PLSVC the venous system and there is the possibility that in before arriving in the right ventricle. the described patient, PLSVC was an incidental The need for an active fixation lead in pacing finding in a patient with a mutation that causes only patients with a persistent left superior vena cava has skeletal anomalies. been stressed in the literature [6]. What has not been However, our patient had also history of syncope described is the extreme difficulty involved in removand abnormalities in the conduction system. The ing the pacing lead through this anomalous vessel, electrophysiological study showed abnormal insuch as we encountered in our case. This was traventricular conduction and rapid right atrial pacing probably due to the existence of a valve in the PLSVC, or to stenosis at the point where it drained into the coronary sinus. The difficulties in removing *Corresponding author. Tel.: 130-1-8048-427; fax: 131-1-804-8427. E-mail address: geros@compulink.gr (G. Filippatos). the conventional lead had a negative effect on the

Aleksandra Zecic - One of the best experts on this subject based on the ideXlab platform.