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.