Holt Oram syndrome: a registry-based study in Europe

Abstract

BackgroundHolt-Oram syndrome (HOS) is an autosomal dominant disorder characterised by upper limb anomalies and congenital heart defects. We present epidemiological and clinical aspects of HOS patients using data from EUROCAT (European Surveillance of Congenital Anomalies) registries.MethodsThe study was based on data collected during 1990–2011 by 34 registries. The registries are population-based and use multiple sources of information to collect data on all types of birth using standardized definitions, methodology and coding. Diagnostic criteria for inclusion in the study were the presence of radial ray abnormalities and congenital heart disease (CHD), or the presence of either radial ray anomaly or CHD, with family history of HOS.ResultsA total of 73 cases of HOS were identified, including 11 (15.1%) TOPFA and 62 (84.9%) LB. Out of 73 HOS cases, 30.8% (20/65) were suspected prenatally, 55.4% (36/65) at birth, 10.7% (7/65) in the first week of life, and 3.1% (2/65) in the first year of life. The prenatal detection rate was 39.2% (20/51), with no significant change over the study period. In 55% (11/20) of prenatally detected cases, parents decided to terminate pregnancy. Thumb anomalies were reported in all cases. Agenesis/hypoplasia of radius was present in 49.2% (30/61), ulnar aplasia/hypoplasia in 24.6% (15/61) and humerus hypoplasia/phocomelia in 42.6% (26/61) of patients. Congenital heart defects (CHD) were recorded in 78.7% (48/61) of patients. Isolated septal defects were present in 54.2 (26/48), while 25% (12/48) of patients had complex/severe CHD. The mean prevalence of HOS diagnosed prenatally or in the early years of life in European registries was 0.7 per 100,000 births or 1:135,615 births.ConclusionsHOS is a rare genetic condition showing regional variation in its prevalence. It is often missed prenatally, in spite of the existence of major structural anomalies. When discovered, parents in 45% (9/20) of cases opt for the continuation of pregnancy. Although a quarter of patients have severe CHD, the overall first week survival is very good, which is important information for counselling purposes.

Defining Features of the Upper Extremity in Holt-Oram Syndrome

“…The difference between our results and those of Newbury-Ecob et al may reflect the fact that our cohort was from hand surgery clinics, whereas their patients came from cardiology and genetics clinics and an upper limb support group. We also found a higher incidence of thumb-index syndactyly compared with the previous reports, 19% vs 5%–11% 1,4 . Newbury-Ecob et al reported 64% of patients had forearm involvement, but details were not provided, and radioulnar synostosis was not mentioned (although limited forearm supination was noted).…”

“…Barisic et al reported involvement of all thumbs in 73 HOS patients 1 , and Newbury-Ecob et al 5 reported 84% of 55 patients with HOS had thumb involvement. We found an intermediate incidence of 95%.…”

“…The incidence of Holt-Oram Syndrome (HOS) is estimated to be about 0.7 in 100,000 live births. 1 The cardiac and limb anomalies vary in presentation.…”

“…While hand and forearm involvement in HOS have been previously described, 1,5 the specific characteristics have not been compared to other forms of RLD. Barisic et al 1 reported on from a European database in 2014, and Newbury-Ecob et al 5 reported from the United Kingdom in 1996, but neither specifically classified the thumb and forearm characteristics in HOS.…”

“…Barisic et al 1 reported on from a European database in 2014, and Newbury-Ecob et al 5 reported from the United Kingdom in 1996, but neither specifically classified the thumb and forearm characteristics in HOS. HOS patients have findings that are not typically seen in RLD, such as syndactyly of the thumb and index finger and forearm synostosis.…”