Ellis-van Creveld Syndrome: A Rare Clinical Report of Oral Rehabilitation by Interdisciplinary Approach
Ellis-van Creveld syndrome (EVC) is a very rare genetic disorder that affects various tissues of ectodermal and mesodermal origin; patients with EVC present with typical oral deficiencies. The affected individuals are quite young at the time of oral evaluation.
It is, therefore, important that these individuals are diagnosed and receive dental treatment at an early age for their physiologic and psychosocial well-being. Albeit there are numerous articles penned on the EVC, the treatise from an oral perspective is inadequate, covering only oral exhibitions and the preventive treatments.
This article reviews the literature and serves as the first disquisition for oral rehabilitation of an EVC patient utilizing surgical, orthodontic, restorative, and prosthodontic management.
Ellis-van Creveld syndrome (EVC) is a rare autosomal recessive disorder with characteristic clinical manifestations, resulting from a genetic mutation in two genes, EVC1 and EVC2, mapping both in locus 16 on the short arm of chromosome 4 (4p16) in a head-to-head configuration [1, 2]. EVC presents with a distinctive tetrad of disproportionate dwarfism, bilateral postaxial polydactyly, ectodermal dysplasia, and congenital heart malformations . It is also known as chondroectodermal dysplasia and mesoectodermal dysplasia; dysplasia is an abnormality in form or development .
Pediatricians Richard W. B. Ellis of Edinburgh and Simon van Creveld of Amsterdam were the first to describe a case of EVC in 1940 . The syndrome had been partially described previously in several reports, but work of Ellis and van Creveld defined it [6, 7]. In literature, detailed description of clinical presentation in finite case series or single reports is found [3–13].
EVC presents with a characteristic tetrad of clinical manifestations :(1)Chondrodysplasia of the long, tubular bones resulting in disproportionate dwarfism, and an exceptionally long trunk is the most common clinical feature, producing a serious ossification defect .
The severity of short limbs increases from the proximal to the distal portions .(2)Bilateral postaxial polydactyly of the hands, with the supernumerary finger, usually being on the ulnar side . Fingers are sausage shaped with wide hands and feet .
(3)Hidrotic ectodermal dysplasia with dystrophic, small dysplastic nails, thin sparse hair, and oral manifestations .(4)Congenital heart malformations in 50% to 60% of cases, the most common being a single atrium and a ventricular septal defect .
The associated cardiorespiratory problems are described as the primary cause of decreased life expectancy in these patients .
According to Winter and Geddes, oral manifestations in EVC are characteristic and remarkable . The most common finding is the fusion of the anterior portion of the upper lip to the maxillary gingival margin, obliterating mucolabial fold, causing the upper lip to present a slightly V-notch in the middle [14, 17].
The anterior portion of the lower alveolar ridge is often jagged . Multiple small accessory labiogingival frenula, serrated incisal edges, diastemas, teeth of abnormal form, enamel hypoplasia, and hypodontia are other features [3, 16].
Varela and Ramos stated that malocclusion is secondary to oral abnormalities and is of no specific type .
2. Clinical Report
A 15-year-old female was referred to the Department of Prosthetic Dentistry for evaluation and prosthetic dental treatment of congenitally absent maxillary lateral incisors and mandibular incisors (Figure 1). The patient was attending a regular school but had concerns about her esthetics.
Pregnancy and delivery were uneventful, and no exposure to radiation or drugs had occurred during pregnancy. At birth, however, the patient presented with short limbs, a long trunk, and polydactyly of hands.
Medical history revealed that the patient has an atrial septal defect and was being planned for surgical closure. Psychomotor development was within the normal range. Extra oral examination showed that the patient has short limb dwarfism (131 cm), with a long trunk and weighed 37.1 kg.
Polydactyly of hands was observed with dysplastic and atrophic finger and toe nails (Figure 2). Hair was thin and sparse.
Intraoral examination showed absence of maxillary lateral incisors, mandibular central and lateral incisors, microdontia of the maxillary left canine, unilateral crossbite on the left side, partial end-to-end occlusal relationship on the right side, and alveolar ridge defect in the anterior mandible (Figure 3).
The examination of soft tissues showed presence of a large maxillary labial frenum attached to alveolar ridge causing obliteration of vestibule and midline diastema. Laterally, there were multiple small accessory labial frenula (Figure 3). The remaining oral mucosa was normal.
A panoramic radiograph confirmed agenesis of the maxillary lateral incisors, mandibular incisors, and all third molars (Figure 4).
Dental procedure that involved manipulation of gingival tissue or perforation of the oral mucosa was performed under proper antibiotic cover, as per revised guidelines from American Heart Association, to prevent infective (bacterial) endocarditis .
Treatment started with supragingival periodontal therapy for removal of plaque and calculus, and to improve oral health.
It was followed by maxillary labial frenectomy and vestibular deepening, using electrosurgery.
Electrocautery procedure offered minimal time consumption, bloodless field during the surgical procedure with no requirement of sutures, and absence of postoperative complications .
Following postoperative healing, orthodontic examination revealed that the patient had a unilateral crossbite on the left side. Cervical Vertebrae Maturation Index (CVMI), using lateral cephalogram (Figure 5), depicted the patient to be in CVMI Stage V [21, 22].
As such, the patient was put on Quad Helix, a slow maxillary expansion appliance, aimed at dentoalveolar expansion of the arch on the left side and correction of partial end-to-end occlusion on the right side [23, 24]. The appliance was fabricated from 36 mil stainless steel wire and was soldered with bands.
Initial activation of 8 mm was done extraorally, and the bands were cemented with glass ionomer cement (Ketac Cem Glass Ionomer Cement, 3M) on maxillary molars (Figure 6). The patient was seen every four weeks for three months unless the appliance achieved 8 mm intraoral activation.
After twelve-week treatment, crossbite was corrected and the appliance was removed. A retention appliance was placed for three months to prevent relapse.
After correction of crossbite, crown build-up, with glass ionomer cement (Vitremer, 3M), was done on the maxillary left canine, to correct microdontia.
Andrew’s Bridge System was designed for rehabilitation of mandibular incisors on lower canines, keeping in view Seibert’s class III ridge defect in the anterior mandible .
Andrew’s Bridge System is a fixed removable prosthesis that is indicated in patients with large ridge defects. It provides maximum aesthetics, is hygienic, and has a good fit with minimal trauma to soft tissues or underlying bone at an economic price [26, 27].
Bar and Clip attachments (Preci-Horix, Ceka) were used to secure removable and fixed component (Figure 7).
Dental implants were planned for maxillary lateral incisors, but the patient was reluctant to undergo invasive treatment option, owing to her concerns about the cardiac defect. Therefore, six units metal ceramic fixed dental prosthesis (Ivoclar Vivadent) was fabricated in the maxillary arch, from canine to canine region, with maxillary canines and central incisors as abutments.
The patient was trained to properly insert and remove the removable prosthesis that was fabricated over the fixed component of Andrew’s Bridge System, and proper oral hygiene instructions (including interdental brush) were given to the patient.
Follow-up was done for six months, and no complication after treatment was noted.
The presentation of medically compromised and syndromic children in the dental office is a great challenge to oral health care providers . Various syndromes are identified earlier in childhood and demand special attention right from the birth . EVC is one of these syndromes with variable phenotype affecting multiple organs .
There is no definitive cure for EVC . The management is multidisciplinary which involves several specialists: a cardiologist, a pediatrician, an orthopedician, a prosthodontist, an oral and maxillofacial surgeon, an orthodontist, and a periodontist [13, 30].
The approach to dental management will depend on each particular case . Preventive measures include dietary counseling, plaque control, oral hygiene instructions, fluoride varnish application, or daily fluoride mouth rinses [3, 6, 31].
To maintain space and to improve function, esthetics, and speech, removable or fixed dental prosthesis (considering age) is recommended .
Restoration of hypoplastic and decayed teeth is indicated to preserve tooth structure and to improve esthetics; taking into account possible presence of enlarged pulp chambers [6, 30]. For soft tissue anomalies, surgical correction is advised .
Parental and child counseling is often required to treat psychological trauma due to compromised oral and medical health .
EVC is a rare autosomal recessive disorder with variable expression, diagnosed by its characteristic clinical manifestations.
Dental and oral manifestations of EVC are definitive; dentist plays a vital role in its early diagnosis and treatment planning and to establish a differential diagnosis with other clinically similar entities.
EVC has high mortality in early life due to cardiac and respiratory problems; those who survive require multidisciplinary treatment planning in terms of preventing oral diseases and providing rehabilitation. Early treatment can help the patient to prevent various problems and undue psychological trauma.
After completion of the treatment, esthetics, function and phonetics improved remarkably. The patient was happy and comfortable with the oral rehabilitation, and the post treatment esthetic outcome helped her to improve her quality of life (Figure 8).
Conflicts of Interest
The authors declare that there are no conflicts of interest regarding the publication of this paper.
The authors acknowledge the support of King Khalid University, Abha, Saudi Arabia, in preparation of this manuscript.
Copyright © 2018 Talib Amin Naqash et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Pyometro Colpos With Low Vaginal Atresia In Ellis –Van Creveld Syndrome
A 17 month old girl presented to the Emergency Department with abdominal pain and distension. She was born premature at 28 weeks and is an only child. There is no history of consanguinity and her parents are not dysmorphic.
She is a known case of Ellis-Van Creveld syndrome and the features present in her are mesomelic dwarfism, polydactyly of both hands and her right foot, dysplastic nails, cleft lip, abnormal frenulae, a small rib cage and hypoplasia of the left lung and an asymptomatic atrial septal defect.
During the neonatal period, she developed neonatal pneumonia which required ventilation and slow recovery. A cleft lip reparative surgery was done at the age of one month to enable her to feed orally. She had been having recurrent episodes of respiratory infections throughout infancy.
Developmentally, there is overall delay in her physical development. She was only able to crawl and at 17 months, her height and weight is at the 50th centile for age.
At the time of presentation, her mother complained that she had developed abdominal colic and foul smelling diarrhoea. There was no associated vomiting.
On examination, she was febrile and her lower abdomen was distended, tender and firm on palpation. The liver and spleen were not palpable. Per rectal examination was normal. Blood investigations revealed a leucocytosis of 15,000/uL.
Renal function was normal. Stool examination for ova and cysts were negative.
Ultrasound of the abdomen revealed a well defined pear shaped mass measuring 12 cm in length, 11 cm wide and 7 cm in antero-posterior diameter, arising from the pelvis, posterior to the urinary bladder and anterior to the rectum with mixed echogenicity and a fluid-fluid level within it (Fig 1). The mass extended inferiorly into the perineum. A normal uterus was not visualized. Her ovaries were not seen. The impression was that this mass was a distended uterus and vagina. The kidneys, liver and spleen were normal. There were no enlarged lymph nodes. No free fluid was detected.
CT scan of her abdomen and pelvis confirmed the mass to be a hydrometrocolpos (Fig 2).
Figure 1. Ultrasound of the abdomen showing a pear shaped structure with thick walls arising from the pelvis, situated posterior to the urinary bladder and anterior to the rectum. There are mixed echoes (white arrows) within it.
Figure 2. CT scan of her abdomen and pelvis (sagittal reformat) showing an enlarged pear shaped fluid filled mass with an air fluid level (yellow arrow) in keeping with an infected hydrometrocolpos. The vaginal appears atretic (white arrow).
On reviewing her skeletal survey, radiographs of her feet revealed a bifid metatarsal and her hands showed extra metacarpal bones and complete duplication of her little fingers. (Fig 3 a). Radiograph of her chest and abdomen showed a narrow thorax with short ribs, and her pelvis showed squared iliac wings with horizontal acetabuli (Fig 3b).
Figure 3 (a) Radiograph of her feet and hands showing bifid metatarsals (right foot) , extra metacarpals (left hand) and polydactyly (both hands and right foot)
(b) Radiograph of her chest and abdomen showing short ribs and a narrow thorax and her pelvis showing squared iliac wings with horizontal acetabuli.
She underwent laparotomy and the uterus and vagina was found to be markedly distended with thick inflamed walls and was filled with foul smelling putrid watery pus. A low vaginal atresia was found to be the cause of the pyometrocolpos. The fallopian tubes and ovaries were normal.
There was no spillage of pus into the peritoneal cavity. Following a vaginal washout, a Raffensperger pull through procedure of the vagina was performed. Post operatively, the child required assisted ventilation for 4 days in intensive care unit and recovered uneventfully.
She remains well.
Hydrometrocolpos is a distension of the uterus (metro) and vagina (colpos) caused by obstruction to drainage of the genital secretions. The spectrum of hydrometrocolpos is broad, ranging from cases undetected until menarche in adolescents to those cases associated with congenital conditions in newborns or infants.
In the latter, agenesis or atresia of the vagina or cervix is responsible for the obstruction. By 8 weeks gestation, the paramesonephric (mullerian) ducts normally meet in the midline to form the uterovaginal canal and this develops into the uterus, cervix and approximately three fourths of the proximal vagina.
The sinovaginal bulbs of the primitive urogenital sinus (vaginal cord) form the distal vagina. Atresia of the lower vagina is attributed to failure of recanalization of the vaginal cord at the 150 mm crown-rump stage. It may take the form of a septum in any plane and at any level, including the site of the hymen, or it may take the form of a stenosis.
The term vaginal atresia is used for cases where there is more than just a simple thin imperforated hymen (1). The inheritance of müllerian defects is ly to be polygenic or multi-factorial, although some syndromes of heritable disorders are described with associated genital and non genital anomalies.
Therefore, although most cases of hydrometrocolpos are sporadic, it may be part of an autosomal recessive condition, known as McKusick-Kaufman syndrome (MKS). MKS is an autosomal recessive disorder characterized by the triad of hydrometrocolpos, post axial polydactyly and congenital heart disease.
Hydrometrocolpos and its association with the syndrome is well described in the literature. MKS must be differentiated from the Ellis Van Creveld (EVC) syndrome, which also includes polydactyly and congenital heart disease, but is associated with chondrodyplasia and ectodermal dysplasia (2).
Here we describe the occurrence of pyometrocolpos secondary to vaginal atresia in a child with EVC syndrome. To our knowledge, there is only one report of vaginal atresia and hydrometrocolpos at birth which required surgery in the neonatal period in a baby with EVC syndrome described by Digilio et al in 1997. Thus the association of hydrometrocolpos with EVC syndrome is rare.
Ellis-Van Creveld syndrome or chondroectodermal dysplasia, is a tetrad of chondrodysplasia, ectodermal dysplasia, polydactyly and congenital heart disease (ASD or a single atrium). Chondrodystrophy of the tubular bones is the most common feature while CNS and urinary tract anomalies are rarer associations (3).
The mode of inheritance is autosomal recessive, associated with mutations in two non homologous genes, both located at chromosome location 4p16 (EVC gene) (4). A high prevalence of EVC syndrome has been reported among certain populations the old order Amish population of Pensylvannia (5).
The radiological features of EVC are delayed skeletal maturation, short acro/ mesomelic limbs, delayed fusion of sutures with large fontanelles, narrow chest with short ribs, small pelvis with flared iliac bones, short sacrosciatic notches, premature ossification of the femoral head epiphyses, proximal tibial metaphyses/epiphyses, genu valgum, pre and postaxial polydactyly and terminal hypoplasia of the fingers, fused carpal bones, slanting and cone shaped epiphyses. Our patient had bifid 5th metacarpals and complete duplication of her little fingers, short ribs, a small chest and a small pelvis with squared iliac wings and horizontal acetabuli. These features support that EVC syndrome is mainly a generalized disorder of the maturation of enchondral ossification (6). Approximately 60% of EVC patients are affected by congenital heart disease and common cardiac defects are ventricular or atrial septal defects and a single atrium. In EVC syndrome, pathognomonic oral and dental manifestations are present. These include abnormal frenulae, delayed eruption of teeth, anodontia, oligodontia, microdontia, abnormal tooth position and shape (7). Ectodermal manifestations include fine hair and absent or thin dysplastic/hypoplastic, discoloured nails of the fingers and toes.
Diagnosis of EVC syndrome in our patient was the clinical and radiological features described which were present in her. Differential diagnosis is made with Jeunés syndrome or asphyxiating thoracic dystrophy and MKK syndrome.
The thoracic cage deformity is usually not so pronounced in EVC syndrome and in Jeunes syndrome, death occurs early in neonatal period from severe respiratory complications. Jeunes syndrome is also distinguished from EVC by the absence of ectodermal dysplasia, cardiac defects and dental anomalies.
EVC and MKK syndrome are clinically similar, but clinical dwarfism due to osteochondrodysplasia and ectodermal anomalies are seen in EVC syndrome. In the rare occurrence of vaginal atresia as in our case of EVC syndrome, the explanation could lie in the course of early development of the genital tract and the skeleton as the syndrome involves all embryonic tissue layers.
The lining of the urethra and urinary bladder is derived from endoderm and the urogenital sinus forms the urethra and vestibule in females. The ectoderm fuses with the endoderm to contribute to patency and canalization of the genital tract. Defects in this process lead to fusion failures and imperforate and obstruction defects.
The skeleton, the mesonephros is also derived from the mesoderm. At about the same stage of development when the embryonic defect in the genitourinary tract occurs, the skeleton develops from adjacent mesodermal cell concentrations and thus may also be damaged.
In summary, we highlight a case of isolated low vaginal atresia leading to infected hydrometrocolpos occuring in a classical case of chondroectodermal dysplasia where chondrodystrophy of the tubular bones and ectodermal manifestations were the predominant features.
There were no other genitourinary abnormalities.
Prompt diagnosis by imaging studies and recognition of the underlying condition prevented further complication of spillage of the infected contents of the uterus and vagina into the peritoneal cavity which could have resulted in increased mortality and morbidity in this child.
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