Sindrome di Holt-Oram (Sindrome cuore-mano tipo I OMIM 142900

Sindrome di Holt-Oram (Sindrome cuore-mano tipo I)  OMIM 142900

La sindrome di Holt-Oram (HOS) è una sindrome autosomica dominante a penetranza completa caratterizzata da cardiopatie congenite e malformazioni agli arti superiori. 

E' dovuta ad alterazioni del gene TBX5 (mappa n 12q24.1) che ha un ruolo nello sviluppo del cuore e dell'avambraccio.
Le anomalie cardiache più frequenti sono il difetto del setto interatriale tipo ostium secondum (DIA), il difetto del setto interventricolare (DIV), anomalie della condizione cardiaca.

Le anomalie scheletriche più comuni sono le anomalie del raggio radiale: ipoplasia o aplasia del radio, pollice a tre falangi, mano torta, a volte assenza del pollice. 

Bibliografia
Holt, M., Oram, S. Familial heart disease with skeletal malformations. Brit. Heart J. 22: 236-242, 1960.
Basson, C. T., Bachinsky, D. R., Lin, R. C., Levi, T., Elkins, J. A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T. A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J. G., Seidman, C. E. Mutations in human TBX5 cause limb and cardiac malformation in Holt-Oram syndrome. Nature Genet. 15: 30-35, 1997. Note: Erratum: Nature Genet. 15: 411 only, 1997.
Basson, C. T., Cowley, G. S., Solomon, S. D., Weissman, B., Poznanski, A. K., Traill, T. A., Seidman, J. G., Seidman, C. E. The clinical and genetic spectrum of the Holt-Oram syndrome (heart-hand syndrome). New Eng. J. Med. 330: 885-891, 1994. Note: Erratum: New Eng. J. Med. 330: 1627 only, 1994.
Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R., Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G., Silengo, M., Pereira, A., Krieger, J., Mesquita, S. F., Kamisago, M., Morton, C. C., Pierpont, M. E. M., Muller, C. W., Seidman, J. G., Seidman, C. E. Different TBX5 interactions in heart and limb defined by Holt-Oram syndrome mutations. Proc. Nat. Acad. Sci. 96: 2919-2924, 1999.
Boehme, D. H., Shotar, A. O. A complex deformity of appendicular skeleton and shoulder with congenital heart disease in three generations of a Jordanian family. Clin. Genet. 36: 442-450, 1989.
Borozdin, W., Bravo-Ferrer Acosta, A. M., Seemanova, E., Leipoldt, M., Bamshad, M. J., Unger, S., Kohlhase, J. Contiguous hemizygous deletion of TBX5, TBX3, and RBM19 resulting in a combined phenotype of Holt-Oram and ulnar-mammary syndromes. Am. J. Med. Genet. 140A: 1880-1886, 2006. 6.         Braulke, I., Herzog, S., Thies, U., Zoll, B. Holt-Oram syndrome in four half-siblings with unaffected parents: brief clinical report. Clin. Genet. 39: 241-244, 1991.
Brons, J. T. J., Van Geijn, H. P., Wladimiroff, J. W., Van der Harten, J. J., Kwee, M. L., Sobotka-Plojhar, M., Arts, N. F. T. Prenatal ultrasound diagnosis of the Holt-Oram syndrome. Prenatal Diag. 8: 175-181, 1988.
Fryns, J. P., Bonnet, D., De Smet, L. Holt-Oram syndrome with associated postaxial and central polysyndactyly: further evidence for genetic heterogeneity in the Holt-Oram syndrome. (Letter) Genet. Counsel. 7: 323-324, 1996.
Gladstone, I., Jr., Sybert, V. P. Holt-Oram syndrome: penetrance of the gene and lack of maternal effect. Clin. Genet. 21: 98-103, 1982.
Glauser, T. A., Zackai, E., Weinberg, P., Clancy, R. Holt-Oram syndrome associated with the hypoplastic left heart syndrome. Clin. Genet. 36: 69-72, 1989. 14.               Gruenauer-Kloevekorn, C., Froster, U. G. Holt-Oram syndrome: a new mutation in the TBX5 gene in two unrelated families. Ann. Genet. 46: 19-23, 2003.
Hurst, J. A., Hall, C. M., Baraitser, M. The Holt-Oram syndrome. J. Med. Genet. 28: 406-410, 1991.
Kantaputra, P. N., Yamasaki, K., Ishida, T., Kishino, T., Niikawa, N. A dominantly inherited malformation syndrome with short stature, upper limb anomaly, minor craniofacial anomalies, and absence of TBX5 mutations: report of a Thai family. Am. J. Med. Genet. 111: 301-306, 2002.
Kuhn, E., Schaaf, J., Wagner, A. Primary pulmonary hypertension, congenital heart disease and skeletal anomalies in three generations. Jpn. Heart J. 4: 205-223, 1963. 
Li, Q. Y., Newbury-Ecob, R. A., Terrett, J. A., Wilson, D. I., Curtis, A. R. J., Yi, C. H., Gebuhr, T., Bullen, P. J., Robson, S. C., Strachan, T., Bonnet, D., Lyonnet, S., Young, I. D., Raeburn, J. A., Buckler, A. J., Law, D. J., Brook, J. D. Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family. Nature Genet. 15: 21-29, 1997.
Mcfarland, J. C., Fallon, J. T. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 51-1980. New Eng. J. Med. 303: 1519-1526, 1980.
Moens, P., De Smet, L., Fabry, G., Fryns, J. P. Holt-Oram syndrome: postaxial and central polydactyly as variable manifestation in a four generation family. Genet. Counsel. 4: 277-280, 1993.
Newbury-Ecob, R. A., Leanage, R., Raeburn, J. A., Young, I. D. Holt-Oram syndrome: a clinical genetic study. J. Med. Genet. 33: 300-307, 1996.
Poznanski, A. K., Gall, J. C., Jr., Stern, A. M. Skeletal manifestations of the Holt-Oram syndrome. Radiology 94: 45-54, 1970. [PubMed: 5410358, related citations]
Ruiz, J. C., Legius, E., Cuppens, H., Moens, P., Marynen, P., Cassiman, J.-J. Exclusion of linkage to 14q23-24 in a family with Holt-Oram syndrome. Clin. Genet. 46: 257-259, 1994.
Rybak, M., Kozlowski, K., Kleczkowska, A., Lewandowska, J., Sokolowski, J., Soltysik-Wilk, E. Holt-Oram syndrome associated with ectromelia and chromosomal aberrations. Am. J. Dis. Child. 121: 490-495, 1971.
Sahn, D. J., Goldberg, S. J., Allen, H. D., Canale, J. M. Cross-sectional echocardiographic imaging of supracardiac total anomalous pulmonary venous drainage to a vertical vein in a patient with Holt-Oram syndrome. Chest 79: 113-115, 1981.
Sletten, L. J., Pierpont, M. E. M. Variation in severity of cardiac disease in Holt-Oram syndrome. Am. J. Med. Genet. 65: 128-132, 1996.
Turleau, C., de Grouchy, J., Chavin-Colin, F., Dore, F., Seger, J., Dautzenberg, M.-D., Arthuis, M., Jeanson, C. Two patients with interstitial del (14q), one with features of Holt-Oram syndrome: exclusion mapping of PI (alpha-1-antitrypsin). Ann. Genet. 27: 237-240, 1984.
 

 

 


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