© 2008 by the American Institute of Ultrasound in Medicine
J Ultrasound Med 27:149-154 • 0278-4297
Three-Dimensional Sonographic Findings Associated With Ectrodactyly–Ectodermal Dysplasia–Clefting Syndrome
Lisa M. Allen, BS, RDMS, RDCS, RVT, APS and
Mary Jo Maestri, MS
Regional Perinatal Center, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, State University of New York Upstate Medical University, Syracuse, New York USA.
Address correspondence to Lisa M. Allen, BS, RDMS, RDCS, RVT, APS, Regional Perinatal Center, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, State University of New York Upstate Medical University, 90 Presidential Plaza, Syracuse, NY 13202 USA. E-mail: allenlm{at}upstate.edu
Abbreviations: EEC, ectrodactyly–ectodermal dysplasia–clefting • 3D, 3-dimensional • 2D, 2-dimensional
 |
Introduction
|
|---|
Ectrodactyly–ectrodermal dysplasia–clefting (EEC) syndrome is a rare autosomal dominant genetic syndrome. This condition is characterized by varying degrees of ectrodactyly and syndactyly of the hands and feet, a cleft lip with or without a cleft palate, and ectodermal dysplasia.1 In addition, abnormalities of the genitourinary system occur frequently in association with this syndrome.2,3 The wide clinical variability of EEC syndrome has been well documented in the literature, and none of the 3 cardinal signs seem to be obligatory.4 We present a case of classic familial EEC syndrome diagnosed by prenatal sonography at 17 weeks’ gestation. In addition to tetraectrodactyly and a unilateral cleft lip and palate, renal dysplasia was noted on serial sonographic evaluation. Three-dimensional (3D) surface rendering was used to supplement traditional 2-dimensional (2D) imaging to further evaluate the fetal phenotype.
|
Case Report
|
|---|
A 42-year-old, woman, gravida 7, para 6, was referred to our facility for prenatal evaluation of her current pregnancy because of a family history of EEC syndrome. The father of the fetus was affected with this rare genetic condition, and 2 of the couple’s 6 children had variable features of the syndrome. The couple received genetic counseling in the past and declined prenatal genetic testing. The patient underwent a sonographic examination and consultation at approximately 17 weeks’ gestation. A complete anatomic survey of the fetus was completed with no major omissions. A left-sided facial cleft was noted, as well as the presence of bilateral ectrodactyly or a "lobster claw" malformation of the hands and feet. On the basis of the family history and clinical sonographic findings, the prenatal sonographic diagnosis of EEC syndrome was made. Three-dimensional evaluation of the 17-week-old fetus provided a crude surface-rendered image of the facial abnormality, and the ectrodactyly of the hands was also noted (Figure 1 ). Another sonographic examination at 22 weeks’ gestation showed that the left kidney appeared highly echogenic, and follow-up was recommended. Additional 2D views of the ectrodactyly abnormality of the hands (Figure 2) and feet (Figure 3) were obtained. Interrogation of the facial cleft was pursued, and a 3D image of the face was created. Because of the lack of substantial fetal fat and muscle deposits at this gestational age, there were technical limitations to the surface details obtained by 3D imaging (Figure 4). At 28 weeks’ gestation, the left-sided cleft lip and palate were evaluated by 2D sonography (Figure 5). Supplemental 3D surface rendering provided considerable improvement in the details of the facial features (Figure 6). The lobster claw appearance of the fetal hands (Figure 7) and feet (Figure 8) was also seen with 3D technology. At 34 weeks’ gestation, the fetal right kidney remained normal in appearance, whereas the left kidney had decreased in size since the prior examination. It was homogeneous in echogenicity without evidence of parenchymal cysts, and Doppler color flow was absent, suggestive of dysplasia.
View larger version (53K):
[in this window]
[in a new window]
|
Figure 1. Three-dimensional surface rendering at 17 weeks’ gestation showing the facial cleft (thick arrow) and ectrodactyly of the left hand (thin arrow).
|
|
View larger version (43K):
[in this window]
[in a new window]
|
Figure 3. Ectrodactyly of the fetal right foot showing the deep median cleft or central ray defect with syndactyly of the remaining digits at 22 weeks’ gestation.
|
|
View larger version (82K):
[in this window]
[in a new window]
|
Figure 4. Three-dimensional surface rendering of the fetal facial cleft at 22 weeks’ gestation. The lack of substantial fat and muscle deposits limits the surface detail.
|
|
View larger version (74K):
[in this window]
[in a new window]
|
Figure 5. Two-dimensional coronal example of the facial cleft (arrow) at 28 weeks’ gestation. LT indicates left; and RT, right.
|
|
View larger version (47K):
[in this window]
[in a new window]
|
Figure 6. Three-dimensional surface rendering showing the left-sided facial cleft with increasing detail 28 weeks’ gestation.
|
|
View larger version (43K):
[in this window]
[in a new window]
|
Figure 8. Three-dimensional surface rendering showing the deep median cleft and surface detail of the fetal right foot at 28 weeks’ gestation
|
|
The patient gave birth to a term male neonate weighing 6 lb 13 oz by elective repeated cesarean delivery. Postnatal photographs were obtained on day 16 of life. The prenatal findings of a unilateral cleft lip and palate (Figure 9) and ectrodactyly of the hands (Figure 10) and feet (Figure 11) were confirmed. Surgical repair of the cleft was scheduled, and no orthopedic intervention for the ectrodactyly was anticipated. A neonatal sonogram of the fetal kidneys was arranged to evaluate the renal abnormality.
View larger version (121K):
[in this window]
[in a new window]
|
Figure 9. Neonatal face showing the left-sided cleft lip and palate. The lobster claw deformity of the left hand is also shown.
|
|
View larger version (121K):
[in this window]
[in a new window]
|
Figure 10. Details of the neonatal right foot, which correlate well with the prenatal 3D surface rendering obtained in Figure 8 .
|
|
|
Discussion
|
|---|
Although the association of ectrodactyly and a cleft lip had been recognized in the literature as early as 1936,5 it was not until 1970 when Rudiger and colleagues1 described these clinical features in combination with ectodermal dysplasia, thus naming the constellation of abnormalities EEC syndrome. The most commonly associated anomalies with this syndrome are fair and thin skin with mild hyperkeratosis and hypoplastic nipples. The hair may be light in color, sparse, thin, and wiry on all hair-bearing areas. The teeth may present with partial anodontia, microdontia, and caries. Features of the eyes include blue irises, photophobia, blepharophimosis, blepharitis, and dacrocystitis. Defects of the lacrimal duct system are present in as many as 84% of affected individuals. Seventy-two percent of EEC syndrome cases will present with a cleft lip with or without a cleft palate. Maxillary hypoplasia and mild malar hypoplasia may also be present. Defects of the midportion of the hands and feet, varying from syndactyly to ectrodactyly, are prominent features, occurring in 84% of cases. There is also an association with mild nail hypoplasia. Genitourinary anomalies are present in 52% of cases, including megaureter, a duplicated collecting system, vesicoureteral reflux, ureterocele, bladder diverticuli, renal agenesis/dysplasia, hydronephrosis, a micropenis, cryptorchidism, and a transverse vaginal septum.6,7 Roelfsema and Cobben8 analyzed 230 published cases of EEC syndrome. Ectrodactyly was noted in 193 patients (84%), ectodermal dysplasia in 178 (77%), facial clefting in 156 (68%), and anomalies of the lacrimal ducts in 135 (59%). In addition, urogenital defects were reported in 52 patients and conductive hearing loss in 33.
The prognosis is excellent, and most individuals are of normal intelligence and adapt reasonably after treatment of the anomalies.6 Orthopedic surgical repairs may be performed on the fingers and toes to correct malformations and to provide optimum function. Treatment and repair of a facial cleft require the coordinated efforts of a multidisciplinary team including pediatricians, dental specialists, surgeons, speech pathologists, and psychologists working together in planning the child’s treatment and rehabilitation. When hydronephrosis is present, intervention may be necessary. Renal surgery may be indicated when pain or an infection is present or kidney function is impaired. Special skin care techniques may be warranted under the direction of a dermatologist; wigs may be desired; and dental treatment including dentures may be required.9 Early and continued ophthalmologic evaluation and management for the defective lacrimal duct system are imperative because chronic dacrocystitis with corneal scarring can be the major debilitating problem in this disorder.6
Genetic counseling for EEC syndrome can be a challenge because of the variability of expression, with reduced penetrance and occasional nonpenetrance.10,11 Currently, EEC syndrome has been linked to 2 genetic locations. The form of EEC syndrome designated EEC1 has been linked to chromosome 7q11.2-q21.3. The second and most common form of this disorder, designated EEC3, is caused by a mutation in the TP63 gene.12 Reports indicate that TP63 mutations have been identified in approximately 93%13 to 98%14 of classically affected patients with EEC syndrome. Genetic analysis is currently available and may be useful in the confirmation of a clinical diagnosis, genetic counseling, and prenatal diagnosis in at-risk pregnancies. With the use of fetal DNA extraction from chorionic villi, South and colleagues15 were the first to provide an example of prenatal DNA diagnosis in a pregnancy at risk for EEC syndrome.
Ectrodactyly–ectrodermal dysplasia–clefting syndrome has been diagnosed sonographically in the early second trimester of pregnancy. In a case reported by Bronshtein and Gershoni-Baruch,16 transvaginal sonography performed at 14 weeks’ gestation showed a bilateral cleft lip and lobster claw deformities of the hands and feet. Additional cases of the prenatal sonographic diagnosis of EEC syndrome have been reported in the literature.17–19 Endovaginal sonography is recommended in the first or early second trimester in the high-risk population. In a low-risk situation, defects of the face, extremities, and genitourinary system can be identified in a routine second-trimester anatomic survey. Three-dimensional surface rendering may be a useful application for evaluating the bony composition of the hands and feet as well as the extent of a cleft lip and palate.
The main sonographic differential diagnosis would include amniotic band syndrome, a split hand–split foot malformation, limb-mammary syndrome, acro-dermato-ungual-lacrimal-tooth syndrome, and Rapp-Hodgkin syndrome.12 These conditions include the potential for facial clefts and varying degrees of malformations of the hands and feet, ranging from syndactyly to ectrodactyly. Additionally, possible clinical components of a few of the above syndromes would be various manifestations of ectodermal dysplasia, which are not shown on prenatal sonography.
This report describes serial evaluation of a classic case of EEC syndrome by prenatal sonography using both 2D and 3D applications. Multiple images are presented to compare 2D and 3D applications and to show the benefits and limitations of serial 3D surface rendering in this particular case. To our knowledge, a case of prenatal diagnosis of EEC syndrome by 3D surface rendering has not been reported previously. Although 3D sonography was not essential for the diagnosis in this particular case, the technique provided detailed images that were beneficial to the parents by providing them with visual confirmation of the recurrence of the EEC syndrome in this pregnancy. The clinical features, management, prognosis, molecular genetics, and differential diagnosis of EEC syndrome have been briefly reviewed.
|
Footnotes
|
|---|
Received July 6, 2007, from the Regional Perinatal Center, Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, State University of New York Upstate Medical University, Syracuse, New York USA. Revision requested July 31, 2007. Revised manuscript accepted for publication August 13, 2007.
|
References
|
|---|
- Rudiger RA, Haase W, Passarge E. Association of ectrodactyly, ectodermal dysplasia, and cleft lip-palate. Am J Dis Child 1970; 120:160–163.[Medline]
- Maas SM, de Jong TPVM, Buss P, Hennekam RCM. EEC syndrome and genitourinary anomalies: an update. Am J Med Genet 1996; 63:472–478.[Medline]
- Rollnick BR, Hoo JJ. Genitourinary anomalies are a component manifestation in ectodermal dysplasia, ectrodactyly, cleft lip/palate (EEC) syndrome. Am J Med Genet 1988; 29:131–136.[Medline]
- Kuster W, Majewski F, Meinecke P. EEC syndrome without ectrodactyly? Report of eight cases. Clin Genet 1985; 28:130–135.[Medline]
- Cockayne EA. Cleft palate, hare lip, dacrocystitis, and cleft hand and feet. Biometrika 1936; 28:60–63.[Free Full Text]
- Jones KL (ed). Smith’s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: WB Saunders Co; 1997.
- Rodini ESO, Richieri-Costa A. EEC syndrome: report on 20 new patients, clinical and genetic considerations. Am J Med Genet 1990; 37:42–53.[Medline]
- Roelfsema NM, Cobben JM. The EEC syndrome: a literature study. Clin Dysmorphol 1996; 5:115–127.[Medline]
- National Organization for Rare Disorders. Danbury, CT: National Organization for Rare Disorders. Available at: http://www.rarediseases.org.
- Tse K, Temple IK, Baraitser M. Dilemmas in counseling: the EEC syndrome. J Med Genet 1990; 27:752–755.[Abstract]
- Tekin M, Ohle C, Johnson DE, Christmas JT, Bodurtha J. Counseling dilemmas in EEC. Genet Coun 2000; 11:19–24.
- Online Mendelian Inheritance in Man. Bethesda, MD: National Center for Biotechnology Information, National Library of Medicine. Available at: http://ncbi.nlm.nih.gov/omim.
- van Bokhoven H, Hamel BCJ, Bamshad M, et al. p63 gene mutations in EEC syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation. Am J Hum Genet 2001; 69:481–492.[Medline]
- Rinne T, Hamel BCJ, van Bokhoven H, Brunner HG. Pattern of p63 mutations and their phenotypes: update. Am J Med Genet A 2006; 140:1396–1406.[Medline]
- South AP, Ashton GH. Willoughby C, et al. EEC (ectrodactyly, ectodermal dysplasia, clefting) syndrome: heterozygous mutation in the p63 gene (R279H) and DNA-based prenatal diagnosis. Br J Dermatol 2002; 146:216– 220.[Medline]
- Bronshtein M, Gershoni-Baruch R. Prenatal transvaginal diagnosis of the ectrodactyly, ectodermal dysplasia, cleft palate (EEC) syndrome. Prenat Diagn 1993; 13:519–522.[Medline]
- Kohler R, Sousa P, Jorge CS. Prenatal diagnosis of the ectrodactyly, ectodermal dysplasia, cleft palate (EEC) syndrome. J Ultrasound Med 1989; 8:337–339.[Medline]
- Anneren G, Andersson T, Lindgren PG, Kjartansson S. Ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC): the clinical variation and prenatal diagnosis. Clin Genet 1991; 40:257–262.[Medline]
- Chuangsuwanich T, Sunsaneevithayakul P, Muangsomboon K, Limwongse C. Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome presenting with a large nephrogenic cyst, severe oligohydramnios and hydrops fetalis: a case report and review of the literature. Prenat Diagn 2005; 25:210–215.[Medline]
|
|
Top
Introduction
Case Report
