Asian Cardiovasc Thorac Ann 2002;10:336-338
© 2002 Asia Publishing EXchange Pte Ltd
Ellis-van Creveld Syndrome Associated With Thymic Hypoplasia
Haci Akar, MD,
Cüneyt Konuralp, MD1,
Kemal Baysal, MD2,
Fer
at Kolbakir, MD
Department of Cardiovascular Surgery
2 Department of Pediatric Cardiology Ondokuz Mayıs University Faculty of Medicine Samsun, Turkey
1 Department of Cardiovascular Surgery Siyami Ersek Thoracic and Cardiovascular Surgery Center Istanbul, Turkey
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For reprint information contact: Cüneyt Konuralp, MD Tel: 90 216 349 9120 Fax: 90 216 363 3642 email: ckonuralp{at}usa.net Aye Çavu Sokak, No: 7/6, Huri Apt., Suadiye, Istanbul, 81070, Turkey.
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ABSTRACT
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A 16-month-old girl presented with the classic signs of Ellis-van Creveld syndrome. Mitral clefts were repaired by direct suturing. The single atrium was repaired by creating a new septum with a pericardial patch, leaving the coronary sinus in the left atrium. During perioperative exploration, thymic hypoplasia was recognized.
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INTRODUCTION
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Ellis-van Creveld (EvC) syndrome is a rare autosomal recessive disease characterized by skeletal abnormalities (short and narrow thorax, polydactyly, and short stature). In 50% to 60% of cases, there are congenital cardiac defects, the most common being single atrium, endocardial cushion defects, and ostium primum atrial septal defects.1
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CASE REPORT
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A 16-month-old girl was referred to our hospital with multiple extremity abnormalities and recurrent pulmonary infection secondary to congenital cardiac defects. She was born in an area (northern Turkey) with a high prevalence of congenital heart defects, where marriage of first or second-generation cousins is customary, and there was first-degree consanguinity between her parents. Her height was 71 cm (5th percentile according to the Turkish curve) and her weight was 8.8 kg (10th percentile according to the Turkish curve). Vital signs were stable. Cardiothoracic examination showed a small chest and pectus carinatum deformity. The abdominal examination was normal. The patient had disproportionately short extremities (Figure 1
) with polydactyly of the hands and a narrow thorax. No sensory motor deficit was noted. Total blood count and differentials were normal except for elevated hematocrit (52%) and hemoglobin (175 g.L-1). All other routine blood studies were within normal limits. Echocardiography revealed a single atrium with grade +3 mitral valve insufficiency (Figure 2). Cardiac catheterization was not performed as ample information had been obtained via echocardiography to identify the cardiac defects. A conventional karyotype study by GTG-banding (G-banding of trypsin in Giemsa-stained chromosomes) and HRBT (high-resolution banding technique) on peripheral blood showed no morphological or numerical chromosomal abnormality (46,XX), as seen in Figure 3.
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Figure 1. Radiograph showing hypoplasia of the proximal tibial epiphysis, and short tibia and fibula (fibula shorter than tibia). These fndings are characteristic of Ellis-van Creveld syndrome.
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Figure 3. A karyotype study by the G-banding technique ruled out any structural or numerical chromosomal anomaly.
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In the light of these clinical findings and laboratory data, the patient was diagnosed with EvC syndrome and underwent surgical repair via a median sternotomy. It was noted that a rudimentary thymus was located in the anterior mediastinum. No ectopic thymic tissue was discovered on exploration of the pleural cavities. The thymus should be hyperplastic in this age group, however, the thymus tissue was almost nonexistent in this patient. Mitral clefts were repaired by direct suturing (with polypropylene suture), and a new atrial septum was created with a bovine pericardial patch. The suture lines were kept to the right, so the coronary sinus remained in the left atrium. Echocardiography on the 7th postoperative day demonstrated the new septum and no atrioventricular valve stenosis or insufficiency (Figure 4). Some immunological tests were performed postoperatively to evaluate the patient’s immune system. Serum immunoglobulin and complement levels were within normal limits. However, negative delayed hypersensitivity skin tests (with tuberculin and Candida) and a low proliferative response to antigens (Candida and tetanus toxoid) and mitogens (concanavalin A and phytohemagglutinin) were detected. The CD4 level was slightly low. The patient was discharged on the 10th postoperative day, but she returned to the hospital twice within 4 months, due to recurrent pulmonary infection requiring intravenous antibiotics. No serious problems have been encountered subsequently.
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DISCUSSION
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Ellis-van Creveld syndrome, also called chondro-ectodermal dysplasia, displays an autosomal recessive trait.1 This very rare disease is due to a particular anomaly on chromosome 4p16, distal to the genetic marker D4S30007, and within a 17-cM region flanking the genetic locus D4S2366 proximal to the FGFR3 gene responsible for the achondroplasia phenotype.2 It occurs most commonly in the Amish people of Lancaster, Pennsylvania, USA, with an incidence of 5 per 1,000 live births and 2 per 1,000 1iving persons. The disorder has also been described in English, Dutch, Jewish, Turkish, French-Canadian, and a few other people. It is one of the short-rib polydactyly syndromes characterized by: acromelic and mesomelic shortness of the limbs; chondrodysplasia of the tubular bones, resulting in disproportionate dwarfism; postaxial polydactyly; small chest; ectodermal dysplasia; dysplastic nails and teeth; and congenital (mainly conotruncal) heart defects in 75% of cases. Approximately half of the patients die in childhood because of cardiorespiratory complications.2 Other abnormalities may accompany these lesions, such as double-orifice mitral valve, aortic atresia, hypoplasia of the ascending aorta or left ventricle, persistent left superior vena cava, absent septal leaflet of the tricuspid valve, and Ebstein’s anomaly.2–6 Although there are many reports of EvC syndrome in the literature, few cases have undergone open heart surgery.1,3–7 Surgical repair of cardiac defects in these patients is no different to that of simple single atrium or large ostium primum atrial septal defects: the mitral cleft is repaired by direct suturing and the atrial septum is reconstructed with a synthetic or pericardial patch. During insertion of the patch, the coronary sinus can be left in the right atrium or, preferably, the left atrium, to avoid injury to the conduction system.4
In such a young patient, it was unexpected to find a hypoplastic thymus. No previous report of thymus abnormality in a case of EvC syndrome could be found. Thymic hypoplasia is typically seen in DiGeorge’s syndrome and is generally accompanied by failure of parathyroid development (developmental failure of the 3rd and 4th pharyngeal pouches known to receive migrating neural crest cells).8 This condition is marked by a total absence or severe lack of cell-mediated immunity, and often, hypoparathyroidism; 22q11 chromosomal deletion is found in most cases. Developmental defects may also involve the heart (affecting the outflow tract) and great vessels as well as other sites. Abnormalities of the palate, facial dysmorphism (prominent nose, retrognathia), developmental delay, and learning disabilities are frequently found in this disease. In our case, there was no facial anomaly typical of DiGeorge’s syndrome. Normal serum calcium, phosphorus, and alkaline phosphatase levels ruled out hypoparathyroidism. A fluorescence in-situ hybridization probe study (after surgery) showed no microdeletion on chromosome 22. In addition, all skeletal pathology and cardiac defects were similar to EvC cases in the literature. These findings suggest that thymic hypoplasia may be a component of a variant of EvC syndrome, rather than representing another specific disease. Further similar experiences would support this observation.
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Acknowledgments
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We want to express our appreciation to Ibrahim Seki, MD, Emergency Physician at Natchez Regional Medical Center, Natchez, Mississippi, USA, for his commitment.
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REFERENCES
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- Franz C, Mennicken U, Butzler HO, Henscher L. Congenital heart disease in the Ellis-van Creveld syndrome. Review of the literature and report of one case [German]. Z Kinderheilkd
1974;117:127–44.[Medline]
- Santos JM, Pipa J, Antunes L, Neves O, Nascimento C, Cabral C, et al. The Ellis-van Creveld syndrome. Apropos 2 clinical cases. Rev Port Cardiol
1994;13:45–50.[Medline]
- Kamesui T, Seki M, Tsubota M, Endo M, Watanabe S, Sato H. A case of Ellis-van Creveld syndrome with partial atrioventricular septal defect and double-orifice mitral valve [Japanese]. Nippon Kyobu Geka Gakkai Zasshi
1997;45:589–93.[Medline]
- Bednarik B, Bednar O, Medricky O, Navratil J, Olejnik O. Common atrium with malformation of mitral valve and persistent upper vena cava. Successful surgical correction [German]. Thoraxchir Vask Chir
1967;15:69–73.[Medline]
- Nomoto S, Muraoka R, Yokota M, Aoshima M, Kyoku I, Kobayashi A, et al. Two surgical cases of Ellis-van Creveld syndrome with absent septal leaflet of the tricuspid valve, mitral cleft, and primum atrial septal defect [Japanese]. Nippon Kyobu Geka Gakki Zasshi
1982;30:1190–5.
- Chang YC, Wu JM, Lin SJ, Wu MH. Common atrium with Ebstein’s anomaly in a neonate with Ellis-van Creveld syndrome. Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi
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- Asano K, Washio M, Motoyama N, Shiozaki K, Eguchi S. Surgical treatment of single atrium and Ellis-van Creveld syndrome [Japanese]. Kyobu Geka
1966;19:920–7.[Medline]
- Asler J, Kumar V. White cells, lymph nodes, spleen, and thymus. In: Schoen FJ, editor. Pathologic basis of disease. 5th ed. Philadelphia: Saunders, 1994:644–95.
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ABSTRACT
INTRODUCTION
