Holt-Oram syndrome

Smith, Ann T.; Sack, George H.; Taylor, George J.

doi:10.1016/s0022-3476(79)80758-1

Cited by 111 publications

(65 citation statements)

References 29 publications

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“…3 Upper limb abnormalities are always present and most commonly bilateral and asymmetrical (left side more than right). 4,5 They involve structures derived from the radial ray (radius, carpal and thenar bones), which can show aplasia, hypoplasia, fusion or anomalous development. This results in features ranging from limitation in movement, triphalangeal or absent thumbs, foreshortened forearms, to phocomelia.…”

Section: Introductionmentioning

confidence: 99%

“…This results in features ranging from limitation in movement, triphalangeal or absent thumbs, foreshortened forearms, to phocomelia. 1,4 The thumbs are the most commonly affected structure (84%), with radial aplasia/hypoplasia in 64%. Ulnar ray defects have been shown to occur only when the radial ray is involved, and to a lesser degree of severity.…”

Section: Introductionmentioning

confidence: 99%

“…Ulnar ray defects have been shown to occur only when the radial ray is involved, and to a lesser degree of severity. 5 Smith et al 4 showed that the radius was affected in 22/39 cases, but the ulna was only involved in 15/39.…”

Section: Introductionmentioning

confidence: 99%

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TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype

Patel

Silcock²,

McMullan³

et al. 2012

Eur J Hum Genet

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Holt-Oram syndrome (HOS) is a rare autosomal dominant heart-hand syndrome due to mutations in the TBX5 transcription factor. Affected individuals can have structural cardiac defects and/or conduction abnormalities, and exclusively upper limb defects (typically bilateral, asymmetrical radial ray defects). TBX5 mutations reported include nonsense, missense, splicing mutations and exon deletions. Most result in a null allele and haploinsufficiency, but some impair nuclear localisation of TBX5 protein or disrupt its interaction with co-factors and downstream targets. We present a five generation family of nine affected individuals with an atypical HOS phenotype, consisting of ulnar ray defects (ulnar hypoplasia, short fifth fingers with clinodactyly) and very mild radial ray defects (short thumbs, bowing of the radius and dislocation of the radial head). The cardiac defects seen are those more rarely reported in HOS (atrioventricular septal defect, hypoplastic left heart syndrome, mitral valve disease and pulmonary stenosis). Conduction abnormalities include atrial fibrillation, atrial flutter and sick sinus syndrome. TBX5 mutation screening (exons 3-10) identified no mutations. Array comparative genomic hybridisation (CGH) revealed a 48 kb duplication at 12q24.21, encompassing exons 2-9 of the TBX5 gene, with breakpoints within introns 1-2 and 9-10. The duplication segregates with the phenotype in the family, and is likely to be pathogenic. This is the first known report of an intragenic duplication of TBX5 and its clinical effects; an atypical HOS phenotype. Further functional studies are needed to establish the effects of the duplication and pathogenic mechanism. All typical/atypical HOS cases should be screened for TBX5 exon duplications.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype

Patel

Silcock²,

McMullan³

et al. 2012

Eur J Hum Genet

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“…The defects may be unilateral or bilateral, however radius is always affected. In majority of cases the disturbances are observed on the left side of the body [10]. Around 75% of patients with HOS are also affected with cardiovascular disorders [11,12].…”

Section: Discussionmentioning

confidence: 99%

“…Around 75% of patients with HOS are also affected with cardiovascular disorders [11,12]. Most common are atrial septal defect, ventricular septal defect or stenosis of pulmonary vessels [1,10,13]. Beside congenital heart diseases, various arrhythmias including conduction block, are observed [14].…”

Section: Discussionmentioning

confidence: 99%

Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis

Walencka

Jamsheer²,

Surmiak

et al. 2016

Ginekol Pol

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Objectives: Holt-Oram syndrome manifests with defects of upper limbs, pectoral girdle and cardiovascular system. The aim of this paper was to present complex clinical picture of the syndrome and its variable expression on the example of the family diagnosed genetically on the neonatal ward, after proband's prenatal examination. Maretial and methods:Nine family members were tested for TBX5 gene mutation. Results:Four of family members were diagnosed with Holt-Oram syndrome and five had correct genetic test results. The diagnosis allowed to identify a genetic risk family and enabled to provide them with genetic counselling. Conclusions:Diagnosis of Holt-Oram syndrome is possible as early as in prenatal period and it can be verified by genetic tests.

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Variation in severity of cardiac disease in Holt-Oram syndrome

Sletten

Pierpont

1996

Am. J. Med. Genet.

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We describe a family with Holt‐Oram syndrome (HOS) with variable hand and cardiac manifestations. One affected relative had complex congenital malformations of the heart consisting of an endocardial cushion defect and hypoplasia of the left ventricle. The literature from 1974 to 1995 is reviewed. Atrial septal defect is the most common cardiac abnormality (60.3% of 189 cases) occurring singly or in combination with other malformations. Thirty‐three individuals (17.5% of literature cases) have more complex congenital malformations of the heart requiring complicated medical management and extensive cardiac surgery. Many genetic reference sources of HOS indicate that single or less severe cardiac malformations are expected in this disorder. It is important to provide more information about the occurrence and spectrum of severity of malformations of the heart to individuals and families where HOS is present. © 1996 Wiley‐Liss, Inc.

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Holt-Oram syndrome

Cited by 111 publications

References 29 publications

TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype

TBX5 intragenic duplication: a family with an atypical Holt–Oram syndrome phenotype

Clinical expression of Holt-Oram syndrome on the basis of own clinical experience considering prenatal diagnosis

Variation in severity of cardiac disease in Holt-Oram syndrome

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