Holt-Oram Syndrome

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Classification according to ICD-10
Q87.2 Congenital malformation syndromes with predominant involvement of the extremities

Holt-Oram Syndrome

ICD-10 online (WHO version 2019)

The Holt-Oram syndrome - also (for simplicity) called atriodigital dysplasia - is one of the so-called heart-hand syndromes .

It is an autosomal dominant inherited feature based on a genetic mutation caused by malformation of the thumb or the spoke ( clubhand ) and the heart (often Vorhofseptum- and ventricular septal defects is marked).

It was first described in 1960 by the British pediatrician Mary Holt and the cardiologist Samuel Oram.

Frequency of occurrence

The syndrome occurs comparatively rarely, the average frequency of occurrence is around 1: 100,000, with 85% of the cases sporadic due to a new mutation .

root cause

Holt-Oram syndrome is caused by genetic mutations in the gene location 12q23-24.1 (TBX5) on chromosome 12 , which are found in 30 to 70 out of 100 people with the syndrome. Peculiarities in other genes can probably also cause the same symptoms .

It is associated with tripartite thumb polysyndactyly syndrome .

Differential diagnosis

Holt-Oram syndrome is often misdiagnosed. It is important to distinguish it from Okihiro syndrome (caused by peculiarities in the SALL4 gene on chromosome 20 ). The same arm malformations and occasionally heart defects are present here. People with Okihiro syndrome, however, often show a Duane anomaly , i.e. a special form of squint in which one cannot see outward, kidney malformations and / or a wrong position of the kidneys, plus hearing disorders, ear malformations and also foot malformations.

Other peculiarities with very similar symptoms are the thrombocytopenia absent radius syndrome (TAR) (here the thumbs are always preserved, but the radius is missing and the platelet count is lower than usual) and Fanconi anemia (this is where the Chromosomes and a tendency to tumor ).

Be differentiated is also the Pallister-Hall syndrome .


The life expectancy of people with Holt-Oram syndrome is generally not reduced; The main thing here is the type and treatability of the heart defect . The correction of the heart defect and the correction of malformations of the extremities are therapeutically important.


  • B. Leiber: The clinical syndromes. Syndromes, sequences and symptom complexes. Edited by G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7th edition. Urban & Schwarzenberg, 1990, ISBN 3-541-01727-9 , p. 322.

Web links


  • R. Witkowski, O. Prokop, E. Ullrich, G. Thiel: Lexicon of the syndromes and malformations. 7th edition. Springer, Berlin 2003, ISBN 3-540-44305-3 , p. 542 f.

Individual evidence

  1. ^ W. Pschyrembel: Clinical dictionary. 265th edition. Verlag Walter de Gruyter, 2014, ISBN 978-3-11-018534-8 .
  2. M. Holt, S. Oram: Familial heart disease with skeletal malformations. In: British Heart Journal . 22 (1960), pp. 236-242.
  3. emedicine Holt-Oram syndrome
  4. ^ QY Li, RA Newbury-Ecob, JA Terrett et al. a .: Holt-Oram syndrome is caused by mutations in TBX5, a member of the Brachyury (T) gene family . In: Nature Genetics . tape 15 , no. 1 , January 1997, p. 21-29 , doi : 10.1038 / ng0197-21 , PMID 8988164 .
  5. CT Basson, DR Bachinsky, RC Lin a. a .: Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome . In: Nature Genetics . tape 15 , no. 1 , January 1997, p. 30-35 , doi : 10.1038 / ng0197-30 , PMID 8988165 .