Ellis-van Creveld syndrome is an extremely rare genetic disorder. It is characterized by short ribs and polydactyly (multiple fingers). Life expectancy depends on the size of the thorax and the severity of any heart defect.
What is Ellis van Creveld syndrome?
Ellis-van Creveld syndrome is also known as chondroectodermal dysplasia because of the involvement of cartilage tissue and the ectoderm. It was first described in 1940 by two pediatricians, Richard Ellis and Simon van Creveld. In this context, it belongs to a group of disorders called short rib polydactyly syndromes (SRPS for short rib polydactyly syndromes). These syndromes are characterized by strikingly short ribs and underdeveloped lungs. All disorders in this group are genetic and are inherited in an autosomal recessive manner. The same is true for Ellis-van Creveld syndrome. The course of these diseases is often lethal. Ellis-van Creveld syndrome is an extremely rare disease. For example, the worldwide incidence in newborns is estimated to be between 1 in 60,000 and 1 in 200,000. A total of only 150 cases have been described. Yet it is somewhat more common in some communities. Among Aboriginal people in Western Australia and Amish people in Lancaster County, Ellis-van Creveld syndrome is diagnosed more often. One estimate puts the incidence among the Amish in Lancaster County at 1 in 5000 per newborn. According to the latest findings, Ellis-van Creveld syndrome is one of the so-called ciliopathies, along with several other related syndromes.
Causes
Ellis-van Creveld syndrome is an inherited disorder that is inherited in an autosomal recessive manner. Presumably, however, several genetic defects can lead to the onset of this disease. In fact, it has been found that at least two genes on the short arm of chromosome 4 may be involved. These are the genes EVC1 and EVC2. Both genes are located next to each other on chromosome 4 and probably have similar regulatory roles. Thus, in some cases of the disease, the same mutant EVC genes were inherited homozygously from both parents. However, in other cases, the child received both a mutant EVC1 and a mutant EVC2 from each parent. However, all children developed the same symptoms. Since only one mutated gene was found in some individuals, it is assumed that there must be more hereditary factors. Both EVC genes are not only located next to each other on chromosome 4, but also share a common promoter region. This in itself suggests that both genes are involved in similar processes. In most cases, a misplaced start codon causes the disease. This results in a later onset or premature termination of protein biosynthesis, producing a polypeptide chain that is too short. However, there are other mutations in both genes that are inherited in an autosomal dominant manner even in heterozygous transmission. This applies, for example, to Weyers syndrome, which is characterized by bone formation disorders of the hands and face. Overall, Ellis-van Creveld syndrome and related disorders must be assumed to have complex genetics in which additional mutations may be involved.
Symptoms, complaints, and signs
Ellis van Creveld syndrome is characterized by short stature, polydactyly (many-fingeredness), short ribs, pulmonary hypofunction, and congenital heart defects. The fingernails and teeth are dysplastic. Patients usually have six fingers on their hands, with the extra finger next to the digitus mimimus (little finger) facing outward in each case. In about 10 percent of cases, there are also supernumerary toes on the feet. However, there is often a greater distance between the big toe and the second toe. The limbs are shortened. Cleft palate and prenatal tooth eruptions are also occasionally seen. About 60 percent of affected individuals have a congenital heart defect. In most cases, this is an atrial septal defect. However, motor and mental development is not impaired. Even prenatally, ultrasound examinations can detect malformations such as shortening of the long tubular bones, heart defects and six-fingeredness. The narrow thorax causes major respiratory problems in the newborns. Overall, the clinical picture in Ellis-van Creveld syndrome is differentiated.The prognosis of the disease depends on the severity of the lung and heart malformations and the therapeutic measures initiated.
Diagnosis
Ellis van Creveld syndrome can be diagnosed prenatally by ultrasonography. However, it must be differentially diagnosed from several syndromes such as Jeune syndrome, Verma-Naumoff syndrome, Weyers syndrome, and McKusick-Kaufman syndrome. Only genetic testing for EVC1 and EVC2 provides a reliable diagnosis.
Complications
In Ellis-van Creveld syndrome, most patients suffer primarily from multiple fingers and short ribs. Also, the syndrome leads to short stature and malformations of the teeth and fingernails in many patients. The deformities often cause psychological problems and lowered self-esteem. The affected person not infrequently suffers from bullying. In about half of all sufferers, a heart defect is also present. This heart defect can have a negative effect on life expectancy in Ellis van Creveld syndrome. However, the syndrome does not affect the child’s mental and physical development, so thinking is not limited. If the affected person suffers from a narrow thorax, this can lead to breathing difficulties. Ellis van Creveld syndrome cannot be cured, so only symptom relief is possible. In most cases, treatment is limited to correcting the heart defect and the breathing difficulties. Whether this results in a reduced life expectancy depends largely on the extent of the heart defect. However, the affected person is restricted in his or her daily life and cannot perform any physically strenuous activities.
When should you see a doctor?
In most cases, Ellis-van Crefeld syndrome can be diagnosed right before birth or shortly after birth, so an additional diagnosis is usually no longer necessary. However, those affected suffer from a heart defect as a result of the syndrome, so this must be corrected quickly. The further course of the disease and life expectancy thus depend strongly on the severity of the heart defect. A doctor should be consulted if the child suffers from short stature and multiple fingers. Furthermore, regular examinations of the heart are necessary in Ellis van Crefeld syndrome to avoid sudden cardiac death. For this, the visit of a cardiologist is necessary. At a very young age, the syndrome should be treated by a pediatrician. A doctor should also be consulted if the child or the parents suffer from psychological complaints or depression. Furthermore, Ellis-van Crefeld syndrome can lead to breathing difficulties, so a visit to a doctor is also necessary in this case.
Treatment and therapy
Causative therapy for Ellis-van Creveld syndrome is not possible because it is a hereditary condition. However, symptomatic treatment must be given immediately after birth to limit the effects of the constricted thorax and possible cardiac defect. It is especially important to manage the breathing problems caused by the constricted thorax. The cardiac defect requires regular monitoring. The bone deformities should also be checked by an orthopedic surgeon for possible corrective intervention. Furthermore, constant dental care is also necessary. Overall, the prognosis of the disease depends on the status of respiration in the first months of life and the severity of the heart defects. Body size in adulthood cannot be predicted.
Outlook and prognosis
The prognosis of Ellis van Creveld syndrome is largely determined by therapy in the first months of life. Initially, pulmonary hypofunction is the most important factor limiting life expectancy. There is considerable respiratory distress, which requires immediate intensive therapy. If the disease is successfully treated in this phase, the extent of the heart defect plays a major role in life expectancy in the further stages. If these two limiting factors are successfully treated, the patient may well live to a normal age. However, little statistical experience is available because this disease is so rare. It is a hereditary disease that leads to multiple dysmorphias and cannot be cured. Another concern in therapy is to improve the quality of life of patients.Thus, orthopedic measures are used to try to limit the deformation of the bones. Intensive dental care is also necessary. Those affected suffer from multiple limitations and external deformities, which can also lead to psychological problems. If the patients are left alone, depression and suicidal thoughts may occur. As a consequence, complete social exclusion is possible. Therefore, psychotherapeutic care should not be missing in the overall concept of therapy. Due to the rarity of the disease, no conclusive statistical statement can yet be made regarding the success of therapy in improving the quality of life.
Prevention
Ellis-van Creveld syndrome cannot be prevented. If a family history of Ellis-van Creveld syndrome has been diagnosed, genetic counseling should be used to assess the risk to offspring. Because of the autosomal recessive mode of inheritance and the rarity of the mutation, it can be assumed that there is only a very small risk.
What you can do yourself
The options for self-help are very limited for patients with Ellis van Creveld syndrome. Despite all efforts, a cure cannot be expected. It is not possible for the human organism with its self-healing powers to cure the disease or to alleviate the symptoms. In everyday life, it is a matter of finding a way to achieve a good quality of life with the disease. Often, the patient’s life expectancy is shortened. Life planning and structuring of time together should be oriented by the family members accordingly. At the same time, it is important to establish a lifestyle that corresponds as much as possible to a normal life. The psychological support of the patient as well as the close relatives is important in this disease. All those involved need individual support in this situation. In addition to professional help, joint discussions and exchanges within self-help groups can be experienced as enriching and beneficial for coping with everyday challenges. The patient’s self-confidence should be built up through positive experiences. Leisure activities help to promote the strengths of the affected person and to develop a zest for life. Relaxation techniques help to reduce stress and build up mental reserves. Various methods are offered at all ages to develop an inner balance.
