Ellis van Creveld syndrome

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Classification according to ICD-10
Q77.6 Chondroectodermal dysplasia Includes
: Ellis-van-Creveld syndrome
ICD-10 online (WHO version 2019)

The Ellis-van Creveld syndrome (EVC), also known as chondroektodermale dysplasia called, is a very rare autosomal - recessive inherited disease . It belongs to the group of short rib polydactyly syndromes (SRPS for Short Rib Polydactyly Syndrome ).

Clinical picture

Bilateral polydactyly and shortened fingers in an EVC patient.
Five-year-old EVC patient with a long, narrow chest and shortened legs.
The upper incisors are missing in the dentition of this EVC patient. The lower incisors are conical in shape.

Ellis van Creveld syndrome is a chondral and ectodermal dysplasia (chondroectodermal dysplasia). In the affected patients it is characterized by short ribs , polydactyly (multiple fingers), short stature , ectodermal defects and heart defects .

The main external symptoms are short stature, thoracic deformity with shortened ribs, polydactyly, as well as hypo- or dysplastic fingernails and teeth. The polydactyly of the hands is usually bilateral, postaxial (outer) on the ulnar side. Polydactyly also affects the feet in around 10% of patients. Often there is a larger space between the big toe ( hallux ) and the second toe. The extremities usually look plump. The mesomele (middle parts, i.e. forearm or thigh) and acromele (distal parts, i.e. fingers or toes) shortening of the limbs is very common. Very often, patients cannot clench their hands into a fist.

About 60% of patients have a heart defect, usually in the form of an atrial septal defect (ASD). In contrast, cognitive and motor development is normal.

frequency

The global incidence of Ellis-van-Creveld syndrome in newborns is estimated to be about 1: 60,000 to 1: 200,000. It is significantly more common in some populations. For example in the Amish community in Lancaster County, Pennsylvania and the Aborigines in Western Australia . Among Amish people in Lancaster County, the prevalence is around 1: 5000 per new birth. Up to the year 2000 a total of 52 cases in 30 clans were reported there.

Worldwide, there were about 150 documented cases of EVC in 2007. Other sources report 300 cases in 1998.

Genetics and pathology

The autosomal recessive inheritance of Ellis-van-Creveld syndrome

Ellis van Creveld syndrome is inherited as an autosomal recessive trait. The cause is mutations in the genes EVC1 (also called EVC ) and EVC2 . In humans, the two genes are located on chromosome 4 , “head to head” on the gene locus p16. Other genetic factors also appear to have an influence on the disease.

The EVC gene was first found on the short arm of chromosome 4 in 1995. This is an area where other congenital chondrodystrophies also originate. Mutations in this gene have been found in EVC patients in Lancaster County, Central and South America. However, when 58 EVC patients were screened, a homozygous mutation in the EVC gene was localized in only 13 . The remaining 45 patients had no mutation in either or both alleles . A second gene has been identified as the cause of Ellis-van-Creveld syndrome in these patients: EVC2 . It is also on chromosome 4, "head to head" in the immediate vicinity of EVC1 . The two genes are by only 2.6 k B separately. EVC2 is 166.4 kb long and shares a common promoter region with EVC1 , while the two sequences show no significant sequence matches - neither at the protein nor at the nucleus level. Nevertheless, the phenotype in Ellis-van-Creveld syndrome cannot be differentiated on the basis of the mutated gene - EVC1 or EVC2 .

In the sequencing of EVC1 and EVC2 in 65 patients with Ellis-van Creveld syndrome has been one in 20 cases EVC1 mutation (31%) in both alleles, and in 25 cases EVC2 mutation (38%) were found. In the latter, both alleles were affected in 22 cases and only one allele in 3. In the majority of all cases, an incorrectly set stop codon is the cause of the disease. In the remaining 20 patients (31%) no mutation was found in either of the two genes. It is therefore believed that Ellis-van-Creveld syndrome is a heterogeneous genetic disorder. Heterozygous mutations in EVC1 or EVC2 also trigger Weyers syndrome , an acrofacial dysostosis (bone formation disorder of the hands and face), which is inherited in an autosomal dominant manner. The fact that in some cases heterozygous carriers of traits can become ill - these patients only have one defective EVC1 or EVC2 gene in each body cell - suggests complex genetics, in which further mutations in other genes may play a role.

Ellis-van Creveld syndrome, X-ray image of the left hand with ossification disorder of the hamate and cone epiphyses

diagnosis

In prenatal diagnostics , the narrow thorax, the shortening of the long tubular bones, hexadactyly and heart defects can be detected from the late first trimester using fine ultrasound .

Radiological criteria are:

  • Pelvic dysplasia with spurs formation medially on the acetabular roof
  • Premature ossification of the proximal humerus and femoral epiphysis
  • Disproportionately short forearms and lower legs
  • Broadening of the tibia proximally, ossification center displaced medially with a massive genu valgum
  • too short fibula
  • Shortened phalanges with cone epiphyses of the middle and terminal phalanges

Common hexadactyly , carpal bone fusion ( hamate and capitate ), common radial head dislocation and patellar dislocation, postaxial polydactyly.

Differential diagnosis

In the differential diagnosis , the Jeune syndrome , the McKusick-Kaufman syndrome , the Weyers syndrome, the Pallister-Hall syndrome and, above all, the Verma-Naumoff syndrome must be differentiated, as well as the cranioectodermal dysplasia .

A genetic test for EVC or EVC2 offers diagnostic reliability .

therapy

There is currently no cure for Ellis van Creveld syndrome.

The patients need multidisciplinary specialist care from birth. The narrow thorax causes breathing problems in many cases. Possible heart defects must be monitored and treated symptomatically. The bone deformations require regular orthopedic checks. The teeth require specialist dental care. Current recommendations for action have been published for perioperative / anesthesiological management (entry at Orphan Anesthesia).

forecast

The prognosis is determined in the first months of life by the restricted breathing due to the narrowed thorax. Later, any heart defects are the main prognostic factor. The adult height is difficult to predict.

Initial description

In 1940, the two pediatricians Richard Ellis (1902–1966) and Simon van Creveld (1894–1971) described a syndrome in three patients for the first time, which was later named after the two first descriptions. The syndrome has already been partially described in some previous publications. However, Ellis and van Creveld were the first to define it.

further reading

Individual evidence

  1. ↑ a b c d e f g h i G. Baujat, M. Le Merrer: Ellis-van Creveld syndrome. In: Orphanet Journal of Rare Diseases. Volume 2, 2007, p. 27, ISSN  1750-1172 . doi: 10.1186 / 1750-1172-2-27 . PMID 17547743 . PMC 1891277 (free full text). (Review).
  2. ↑ S. Al-Khenaizan, N. Al-Sannaa, AS Teebi: What syndrome is this? Chondroectodermal dysplasia - the Ellis-van Creveld syndrome. In: Pediatric Dermatology . Volume 18, Number 1, 2001 Jan-Feb, pp. 68-70, ISSN  0736-8046 . PMID 11207979 .
  3. ^ RW Ellis, JD Andrew: Chondroectodermal dysplasia. In: J Bone Joint Surg. Volume 44, 1962, pp. 626-636.
  4. ↑ a b c K. Kurian, S. Shanmugam et al: Chondroectodermal dysplasia (Ellis van Creveld syndrome): a report of three cases with review of literature. In: Indian journal of dental research. Volume 18, Number 1, 2007, pp. 31-34, ISSN  0970-9290 . PMID 17347543 . (Review).
  5. ↑ L. Dugoff, G. Thieme, JC Hobbins: First trimester prenatal diagnosis of chondroectodermal dysplasia (Ellis-van Creveld syndrome) with ultrasound. In: Ultrasound in Obstetrics & Gynecology . Volume 17, Number 1, January 2001, pp. 86-88, ISSN  0960-7692 . doi: 10.1046 / j.1469-0705.2001.00255.x . PMID 11244665 .
  6. ^ A b Genetics Home Reference: Ellis-van Creveld syndrome. Retrieved January 9, 2012
  7. ^ VA McKusick: Ellis-van Creveld syndrome and the Amish. In: Nature genetics . Volume 24, Number 3, March 2000, pp. 203-204, ISSN  1061-4036 . doi: 10.1038 / 73389 . PMID 10700162 .
  8. ↑ KM Zangwill, DK Boal, RL Ladda: Dandy-Walker malformation in Ellis-van Creveld syndrome. In: American journal of medical genetics. Volume 31, Number 1, September 1988, pp. 123-129, ISSN  0148-7299 . doi: 10.1002 / ajmg.1320310114 . PMID 3223493 .
  9. ↑ a b M. H. Polymeropoulos, SE Ide u. a .: The gene for the Ellis-van Creveld syndrome is located on chromosome 4p16. In: Genomics. Volume 35, Number 1, July 1996, pp. 1-5, ISSN  0888-7543 . doi: 10.1006 / geno.1996.0315 . PMID 8661097 .
  10. ↑ VL Ruiz-Perez, SE Ide et al.: Mutations in a new gene in Ellis-van Creveld syndrome and Weyers acrodental dysostosis. In: Nature genetics. Volume 24, Number 3, March 2000, pp. 283-286, ISSN  1061-4036 . doi: 10.1038 / 73508 . PMID 10700184 .
  11. ↑ a b V. L. Ruiz-Perez, SW Tompson a. a .: Mutations in two nonhomologous genes in a head-to-head configuration cause Ellis-van Creveld syndrome. In: American Journal of Human Genetics . Volume 72, Number 3, March 2003, pp. 728-732, ISSN  0002-9297 . PMID 12571802 . PMC 1180248 (free full text).
  12. ↑ M. Galdzicka, S. Patnala u. a .: A new gene, EVC2, is mutated in Ellis-van Creveld syndrome. In: Molecular Genetics and Metabolism. Volume 77, Number 4, December 2002, pp. 291-295, ISSN  1096-7192 . PMID 12468274 .
  13. ↑ a b S. W. Tompson, VL Ruiz-Perez u. a .: Sequencing EVC and EVC2 identifies mutations in two-thirds of Ellis-van Creveld syndrome patients. In: Human genetics. Volume 120, Number 5, January 2007, pp. 663-670, ISSN  0340-6717 . doi: 10.1007 / s00439-006-0237-7 . PMID 17024374 .
  14. ↑ Bernfried Leiber (founder): The clinical syndromes. Syndromes, sequences and symptom complexes . Ed .: G. Burg, J. Kunze, D. Pongratz, PG Scheurlen, A. Schinzel, J. Spranger. 7., completely reworked. Edition. tape 2 : symptoms . Urban & Schwarzenberg, Munich et al. 1990, ISBN 3-541-01727-9 .
  15. ↑ F. Hefti: Pediatric Orthopedics in Practice. Springer 1998, ISBN 3-540-61480-X , page 654
  16. ^ NCBI: EVC-Related Ellis-van Creveld Syndrome. Retrieved January 9, 2012
  17. ^ NCBI: EVC2-Related Ellis-van Creveld Syndrome. Retrieved January 9, 2012
  18. ↑ Archived copy ( memento of the original dated December 1, 2017 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. @1@ 2Template: Webachiv / IABot / www.orphananesthesia.eu
  19. ^ RW Ellis, S. van Creveld: A Syndrome Characterized by Ectodermal Dysplasia, Polydactyly, Chondro-Dysplasia and Congenital Morbus Cordis: Report of Three Cases. In: Archives of Disease in Childhood. Volume 15, Number 82, 1940, pp. 65-84, ISSN  0003-9888 . PMID 21032169 . PMC 1987729 (free full text).
  20. ↑ A. Cahuana, C. Palma et al .: Oral manifestations in Ellis-van Creveld syndrome: report of five cases. (PDF; 641 kB) In: Pediatric dentistry. Volume 26, Number 3, 2004 May-Jun, pp. 277-282, ISSN  0164-1263 . PMID 15185812 .
  21. ↑ M. Atasu, S. Biren: Ellis-van Creveld syndrome: dental, clinical, genetic and dermatoglyphic findings of a case. In: The Journal of clinical pediatric dentistry. Volume 24, Number 2, 2000, pp. 141-145, ISSN  1053-4628 . PMID 11314324 . (Review).

Web links

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