JOURNAL OF COMMUNITY MEDICINE

INDIAN ASSOCIATION OF PREVENTIVE AND SOCIAL MEDICINE ORISSA CHAPTER

Assistant Professor, Department of medicine, & Project Coordinator & Principal Investigator, Sickle Cell Research Project,

** Assistant Professor, Department of Medicine, & Coinvestigator,

Sickle Cell Research Project,

*** Professor & H.O.D., Department of Medicine,

**** Research Assistant & PhD Scholar, Sickle Cell Research Project,

VSS Medical College, Burla, Sambalpur Orissa,

Email: drdilippatel25@gmail.com

D.K.Patel, P.K.Mohanty, P.K.Padhi, R.S.Mashon, S.Patel, S.K.Jena

Abstract

 

A rare combination of two autosomal recessive disorders, namely “Ellis-van Creveld (EvC) syndrome” and Sickle Cell hemoglobinopathy is being reported; first of its kind in world literature. The patient had short limbed dwarfism, postaxial polydactyl in hands, dysplastic nails and few peg shaped teeth as well as congenital missing of teeth. The patient had also a rare association of dyserythropoietic anaemia. Two other family members were also having features of EvC syndrome.

 

Keywords: Ellis-van Creveld syndrome, Sickle cell hemoglobinopathy, Autosomal recessive disorders, Dyserythropoiesis.

 

Introduction

Ellis-van Creveld (EvC) syndrome also called chondro-ectodermal dysplasia is a rare autosomal recessive disorder due to mutation in EVC and EVC-2 genes located in chromosome 4, characterized by short limbed dwarifism, post axial polydactyly, dysplastic teeths and nails, and cardiac defects^1,2,3. Other features include partial harelip and multiple frenulae in lips; short ribs and narrow chest; genital abnormalities like epispadius, hypospadius and cryptorchidism; low iliac wings with spur like projections at acetabula and genu valgum. Sickle cell hemoglobinopathy is another autosomal recessive disorder due to point mutation in 6^th position of beta globin gene inchromosome 11⁴. In heterozygous stat it is generally asympotomatic whereas homozygous stat manifests with chronic hemolytic anaemia, organ dysfunction and life threatening emergencies called ‘crises’. Here we report a patient of Ellis-van Creveld syndrome associated with sickle cell hemoglobinopathy which is a rare combination. Two other family members with Ellis-van Creveld syndrome are also reported in this study.

 

Case Report

An eighteen years old young female (PJ) presented to the Department of Medicine VSS Medical College, Burla in November’05 for breathlessness on moderate physical exertion and easy fatigability of one month duration. She had also pain in epigastrium of fifteen days duration. She had no significant illness in past except that she was born with short limbs and six fingers in each hand. She had short stature which was apparent from one year of age. Her school performance was average. She attained menarche at the age of seventeen years and having normal menstrual cycles since then. Her elder sister (SJ), also, was having short stature. Her only brother and parents had normal height. Her mother died of some unknown illness fifteen years back.

 

 

 

 

 

 

 

 

 

 

 

                         

 

                          Fig.-1                                                                    Fig.-2

 

 

 

 

 

 

 

 

 

 

 

 

                          Fig.-3                                                                    Fig.-4

 

On examination, the index case (PJ) was found to have a short stature with a height of 118cm (Fig. 1). Examination of hands revealed six digits in each with broad and shortened distal phalanx in all the fingers (Fig. 2). There were five toes on right foot whereas there was syndactyly in the left foot with fusion of 3^rd and 4^th toes (Fig. 3). There was hallux valgus in both feet with shortening of middle and distal phalanges of the toes. The finger and toe nails were small and brittle (Fig. 2,3). Oral cavity examination revealed peg shaped medical incisors in upper jaw and lateral incisors in lower jaw with missing of other teeth; there were multiple frenulae joining inside of upper and lower lips with gum (Fig. 4). The patient had severe pallor. Examination of cardio-respiratory system revealed increased antero-posterior diameter of chest and a haemic murmur. Other systems were normal.

 

On investigation, the hematological parameters were as follows: hemoglobin 3.4 gm/dl, TLC 12,000/cmm, platelet count 2.2 lacs/cmm, dimorphic blood picture on peripheral smears study and dyserythropoiesis on bone marrow examination. Sickling test, hemoglobin electrophoresis and chromatography showed the patient as having sickle cell traint. Skeletal radiology of upper limb revealed shortening of ulna, fusion of carpal bone capitate and hamate, six metacarpals and short middle and distal phalanges on both side. Radiological examination of the lower limb revealed depressed and flattened lateral compartment of upper end of tibia on both sides giving rise to genu valgum, shortening of upper end of fibula, five metatarsals and separate phalanges on both side. Chest radiography, electrocardiography and echocardiography did not reveal any cardiac abnormality. A final diagnosis of Ellis-van Creveld syndrome with sickle cell trait was made.

 

The elder sister of the patient and her uncle’s grandson had also clinical features compatible with EvC syndrome. The elder sister (SJ), aged 25 years, had short stature with a height of 121cm, shortening of the limbs, symmetric postaxial polydactyly with six fingers in each hand and six toes in each feet with fusion of 5^th and 6^th toes on right side. She had also knock knees. Her finger and toe nails were small and dysplastic. Dental examination revealed only four teeth in upper jaw and eight in lower jaw; all were peg shaped. The grandson of the patients’ paternal uncle aged one year also showed some of the above features. He had short limbs and six toes in both feet with overlapping of fifth and sixth toes on left side. The nails were dysplastic in both toes and fingers. Cardiovascular system examination in both of these cases revealed no abnormality.

 

Discussion

Ellis-van Creveld syndrome (EvC) was first described by Richard W.B. Ellis of Edinburgh and Simon van Creveld of Amsterdam in 1940¹. It is a rare form of autosomal recessive disease characterized by skeletal dysplasia with an incidence of 1 in 1,50,000 live births⁵. However, a very high incidence of 5 per 1000 live births is reported in old order Amish population⁶. An internet search of the Indian literature till January’2006 revealed that a total of 23 cases have been reported from various parts of India. The case reported by Satpathy and Behera way back in 1969 from Medical College Hospital, Berhampur belonged to Ichhapur, Andhra Pradesh⁷. Ours is the first case report of three patients of eEvC syndrome in a family of western Orissa. Interestingly, first of these cases was also a heterozygous carrier of sickle cell gene. Sickle cell hemoglobinopathy is common in western Orissa with a gene frequency of 15 percent in certain caste Hindus⁸.

 

The first patient had typical clinical features of EvC syndrome, namely short limbed dwarfism, postaxial polydactyly in hands, nail dysplasia and dental abnormalities. This patient also had knock knees, hallux valgus and syndactyly in both feet as reported in various literatures. However, some of the atypical features noted in this patient were non uniform acromesomelia (i.e., shortening of distal and middle phalanx) in hands and hallux valgus. Kagalwala et al found hallux valgus only in one of the five cases they have reported⁹. Although cardiac abnormality is being reported in 50% of cases of EvC this case had no cardiac abnormality. Similarly the other two patients in this series had polydactyly in both the feet which are seen only in less than 10% of cases⁹.

 

Radiological examination of the first case revealed various abnormalities namely shortening of the ulna, fusion of capitates and hamates, epiphytical growth failure at upper lateral compartment of tibia and shortened fibula, in addition to six metacarpals in each hand and short middle and distal phalanges in both hands. Hematological examination revealed two rare associations. The first case had severe anaemia with dimorphic blood picture and dyserythropoetic marrow. Scurlock D. et al reported the first case of EvC associated with dyserythropoetic anaemia in 2005¹⁰. This is the second case reported with such association. In addition this patient also had sickle cell trait. To the best of our knowledge this association of Sickle cell hemoglobinopathy and Ellis-van Creveld syndrome, both of which are autosomal recessive in nature is first of its kind in world literature.

 

The possible reaon for the rare association of Ellis-van Creveld syndrome with sickle cell hemoglobinopathy could be due to the common occurrence of consanguineous marriage in this part of Orissa which is an important factor for recessive heritable disorders. Further epidemiological study is needed to ascertain the prevalence Ellis-van Creveld syndrome in western Orissa.

 

References

1. Ellis RWB, van Creveld s. A syndrome characterized by ectodermal dysplasia, polydactyly, chondrodysplasia and congenital morbus cordis. Report of three cases Arch dis child 1940; 15:65-84.

2. Ruiz-Perez VL., Tompson SWJ, Blair HJ, Espinoza-Valdez C, lapuzina P, Silva EO, Hamel B. Gibbs JL, Yong ID, Wright MJ, Goodship J. Mutations in two non homologuous genes in a head to head configuration cause Ellis-van Creveld syndrome. Am j Hum Genet 2003; 72(3): 728-732.

3. Ye X, Song G, Fan M, Shi L, Jab E.W. Huang S, Guo R, Bian Z. A novel heterozygous deletion in EVC 2 gene causes Weyer’s acrofacial dysostosis. Hum Genet 2006: 11: 1-7.

4. Benz EJ. Hemoglobinopathies. In: Kasper DL, Braunwald E, fauci AS, Hauser SL, Longo DL, Jameson JL Eds harrison’s Principles of Internal medicine, 16^th edn, New York, McGraw Hill Inc., 2005; pp 593-601.

5. Popli MB, Popli V. Ellis-van Creveld syndrome, 1nd j Radiol Imag 2002; 12(4): 549-550.

6. McKusick VA, Egeland JA, Eldridge R, Krusen DE. Dwarfism in Amish: I. The Ellis-van Creveld syndrome. Bull John Hopkins Hosp. 1964; 115:306.

7. Satpathy RK, Behera SK. Ellis-van Creveld syndrome. Indian j pediatr 1969; 36: 445-446.

8. Kar BC Sickle cell disease in India. J Assoc Physicians Ind 1991; 39:954-960.

9. Kagalwala TY, Vaidya VU, Joshi RM, Bharucha BM, Kumta NB. Chondro-Ectodermal dysplasia. Indian Pediatr 1987; 24(11): 1045-1050.

10. Scurlock D. ostler D, Nguyen A, Washed A. Ellis-van Creveld Syndrome and dyserythropoesis. Arch pathol Lab Med 2005; 129(5): 680-682.

ELLIS-VAN CREVELD SYNDROME WITH SICKLE CELL HEMOGLOBINOPATHY AND DYSERYTHROPOIESIS: A RARE COMBINATION