Van Creveld Syndrome Research Articles

The Gene for the Ellis–van Creveld Syndrome Is Located on Chromosome 4p16

Ellis–van Creveld syndrome (EVC) is an autosomal recessive disorder characterized by disproportionate dwarfism, polydactyly, and congenital heart disease. This rare disorder is found with increased frequency among the Old Order Amish community in Lancaster County, Pennsylvania. We have used linkage analysis to localize the gene responsible for the EVC phenotype in nine interrelated Amish pedigrees and three unrelated families from Mexico, Ecuador, and Brazil. We now report the linkage for the Ellis–van Creveld syndrome gene to markers on the distal short arm of human chromosome 4, withZmax= 6.91 at θ = 0.02 for marker HOX7, in a region proximal to theFGFR3gene responsible for the achondroplasia phenotype.

Single-strand conformation polymorphism analysis of human decorin, biglycan and fibromodulin cDNAs

The coding regions of the human decorin, biglycan and fibromodulin cDNAs have been examined utilizing the method of single-strand conformation polymorphism analysis. Analysis of total RNA from a group of eight human skin fibroblast cell lines did not detect any sequence variations in the decorin cDNA. In contrast, the analysis detected three sequence variations in the biglycan cDNA and one in the fibromodulin cDNA from the same group of cell lines. For the biglycan cDNA, one variation involved a position in the 5'-untranslated region, while the other two affected the wobble bases of triples encoding serine residues 10 and 143 of the mature core protein. For the fibromodulin cDNA, the variation involved the wobble position of the codon for glutamic acid residue 61 of the putative mature core protein. Single-strand conformation polymorphism analysis of these proteoglycan cDNAs was also applied to study patients exhibiting a variety of connective tissue pathologies, including chondrodysplasia punctata, Desbuquois syndrome, Dyggve-Melchior-Clausen syndrome, dyssegmental dysplasia, Ehlers-Danlos syndrome types I and III, Ellis van Creveld syndrome and thanatophoric dysplasia, though no additional sequence variations were detected.

Ellis--Van Creveld syndrome.

The last two cases of Ellis van Creveld syndrome diagnosed in the Neonatology Service of our department are presented and the clinical and radiological features described. One of the children, the boy, was suffering from ocular malformations which are not common in this syndrome. Both have heart malformations which are frequent in this syndrome. Paradoxically the boy, who was quite below the third percentile in height, has less alterations in the long bones than did the baby girl, who was within the normal height range. Attention is called to the lack of adipose panniculus in the boy, but the girl's weight is within the normal limits. Both died because of the heart anomalities with accompanying respiratory distress.

Difficulties in differentiation between chondroectodermal dysplasia (Ellis--van Creveld syndrome) and asphyxiating thoracic dystrophy.

SummaryTwo cases of Ellis van Creveld syndrome– one with normal, one with elongated narrow thorax–and two cases of Asphyxiating Thoracic Dystrophy–a localised form and a generalised mild form are described.The morphological differences and similarities in Ellis van Creveld syndrome and Asphyxiating Thoracic Dystrophy syndromes are described and the mutual relationship of both diseases is discussed.

The epidemiology of congenital heart disease

During the past 30 years the mortality rates for congenital malformations of the circulatory system in the white population of the United States have declined in those under 1 year and increased slightly in those aged 1–14 years. In the nonwhites there has been an increase in both groups. The incidence of congenital heart disease in the United States, United Kingdom and Sweden is about 5 per 1000 births. At least 20,000 babies with congenital heart disease will probably be born each year in the United States. Genetic factors explain some cases of congenital heart disease. A few cases have been known to occur in association with arachnodactyly, Ellis' and van Creveld's syndrome and mongolism. Apart from mongolism, congenital heart disease has sometimes been found to be associated with chromosomal abnormalities. The incidence of the disease in relatives of patients with congenital heart disease is higher than the incidence in the general population. The degree of familial aggregation appears to vary with the particular type of malformation, being higher in pulmonary valvular stenosis and patent ductus arteriosus than in Fallot's tetralogy or interventricular septal defect. Malformation in systems other than the cardiovascular are more common in propositi with congenital heart disease and in their relatives. These malformations are more often found in association with cyanotic types of congenital heart disease than with acyanotic types. Certain types of congenital heart disease may be due to recessive inheritance, but consanguinity is clearly unimportant in the etiology of the majority of cases. Twin studies have usually shown a lack of concordance of congenital heart disease in monozygous pairs, another indication that genetic factors cannot be wholly responsible in the majority of cases. Environmental factors explain some of the cases. The original Australian studies linking congenital malformations with rubella frequently noted congenital heart disease. Women who have developed rubella in pregnancy have shown an increased risk of congenital heart disease, mainly from the 5th to the 9th week when the heart is rapidly developing. Patent ductus arteriosus is the most common defect; septal defects, pulmonary valvular stenosis, and Fallet's tetralogy occur less often. Congenital heart disease occurred with undue frequency, usually in association with other abnormalities, in children of women treated with thalidomide during pregnancy. High frequencies of certain forms of congenital heart disease have been found in people living at high altitudes; this has supported the suggestion that anoxia is an important factor in this disease. Radiation also appears to be a possible factor in the production of congenital heart disease. Certain types of congenital heart disease appear to be more common in children born at certain times of the year. Most studies have failed to support this hypothesis and other explanations have been advanced, for example, hours of daylight, amount of sunshine and temperature. No consistent associations have been shown between congenital heart disease and parental age, birth order or social class. In the majority of cases of congenital heart disease neither genetic nor environmental factors can as yet be implicated. The search for environmental factors would appear to offer the most promising line of epidemiological research. Studies of pregnant women and women who have already borne a malformed child should prove fruitful. Variation in frequency of congenital heart disease in relation to race, geography, altitude, background irradiation, and epidemic patterns are relevant to current etiological patterns.

Single atrium and the Ellis—van Creveld syndrome

Congenital heart disease has been encountered in over half of the reported cases with the Ellis—van Creveld syndrome and when present appears to be the main determinant of longevity. A case with typical findings of the syndrome with single atrium and defects consistent with partial persistent atrioventricularis communis is presented. Review of case reports with postmortem study indicated single atrium to be a relatively frequent finding. The possible incidence of persistent atrioventricularis communis type defects is also noted.