Abstract
Ectrodactyly is a rare dominant autosomal malformation with variable expression. Herein we report a case early diagnosed by ultrasound at 15 weeks of gestation of isolated ectrodactyly involving the four limbs. The sonographic findings were bilateral split hands and split foot. Diagnosis of typical isolated ectrodactyly was pathologically confirmed. Clinical forms, pathogenesis, differential diagnosis, and early prenatal diagnosis are discussed.
Keywords: Ectrodactyly, early prenatal diagnosis, ultrasound
Introduction
For centuries, human morphologie anomalies of limbs have been the subject of both public curiosity and scientists’ scrutiny (Paracelso 1536, Saint Hilaire 1818, Ballantyne 1904, Warkany 1971) [I].
The term ectrodactyly refers to a group of congenital malformations characterized by a cleft splitting the hands and feet into two halves due to aplasia and/or hypoplasia of phalanx, metacarpal and/or metatarsal bones of one or more fingers or toes. This anomaly is also referred as split hand and foot syndrome and/ or “lobster claw” deformity.
From a embryological point of view, upper limb buds (primordia) are seen as early as at 5 weeks of gestation, whereas those for lower limbs are noted at 6 weeks. Thereafter, mesenchymal proliferation results in limb bud elongation. Then, the ectoderm covering the tip of each bud becomes thickened, forming the ectodermal apical edge, from which the limb will be developed. Upon the 6th week, completed, mesenchymal condensation forms digital rays on the hand plate. Next, interradial mesenchyma splits, resulting in clefts between digital rays. As tissue programmed death or interdigital degeneration proceeds, fingers and toes are not short and membranous in nature any longer, becoming well differentiated and spaced. Blockade of the aforementioned molecular and cellular process between the 6th and 7th gestational week would cause congenital anomalies such as syndactyly and ectrodactyly [2].
From a sonographic point of view, limb buds can be seen transvaginally at 8 weeks of gestation, and at 11-12 weeks, joints of upper and lower limbs, fingers and toes are visible. We report a case of typical isolated ectrodactyly inherited in an autosomal dominant pattern, diagnosed early by ultrasound at 15 weeks of gestation.
Case report
A 39-year-old secundigravida 14-week pregnant woman was referred to our hospital from a secondary health care center as a routine scan performed transabdominally suggested a malformation of the limbs. Her first pregnancy and delivery were uneventful. Medical records included ectrodactyly in the patient’s father and sister and in the patient herself. History taking ruled out toxic habits and consanguinity. At 15 weeks ultrasound examination revealed an ectrodactyly involving the four limbs with abnormal clefts in hands and feet between the second and fourth metacarpal/metatarsal bones and corresponding soft tissues (Figure 1).
Figure 1. Hand with ectrodactyly showing a central defect between both fingers.
Biometry results matched to gestational age and associated abnormalities were ruled out. After genetic counseling, the parents refused the karyotype analysis and chose to terminate the pregnancy. Postmortem karyotype analysis showed that the fetus was euploid.
The ultrasound diagnosis of isolated typical ectrodactyly was confirmed by postmortem study, an ectrodactyly of all the extremities was found. There were no further internal or external associated abnormalities.
Discussion
Distal limb congenital malformations can be observed either as isolated anomalies involving hands and feet or in the setting of specific syndromes or chromosomal aberrations.
There are two distinctive clinical forms of isolated ectrodactyly: the typical and the atypical forms. The former (incidence rate: 1 in 90,000 births) is a dominant autosomal anomaly and involves lack of both phalangeal and metacarpal bones, which results in a deep V-shaped defect clearly splitting the hand in two halves, one being cubital, the other one radial in nature. The condition is also referred as “lobster claw” deformity because the cubital and radial parts of the hand resemble a claw. However, at times the radial ray aberration may also result in monodactyly with no cleft [3,4]. The atypical form (incidence rate 1 in 150,000 births), involves a much wider cleft resulting from a defect of metacarpal bones of medial fingers/toes [3] with a U-shaped central defect. While ectrodactyly pathogenesis remains to be elucidated, there is evidence suggesting that five loci, in which the mutation resides, may play a role. Candidate chromosomes are the chromosome 7 (critical points at 7qll.2-q21.3) (SHFMl), chromosome X (Xq26) (SHFM2), chromosome 10 (10q24)(SHFM3), chromosome 3 (3q27) (SHFM4), and chromosome 2 (2q31)(SHFM5) [5-7].
Although ectrodactyly can appear either as an isolated malformation or associated with the amniotic band syndrome, most commonly it is a component of the ectrodactylyl-ectodermal dysplasia- cleft lip/palate syndrome (EEC). The EEC syndrome is inherited in a dominant autosomal fashion with incomplete penetrance and variable expression. It involves all four limbs, particularly the hands which present severe deformities. The spectrum of ectodermal defects is broad, including dry skin and impairment of hair, nails, teeth, and nasolacrimal and sweat ducts. Intelligence is most often within normality. Some cases of EEC inherited in a recessive autosomal fashion have been described in the literature [8].
The differential diagnosis of typical isolated ectrodactyly should include other conditions presenting with ectrodactyly, such as Karsch-Neugebauer’s syndrome (hand and foot cleft with congenital nystagmus), Fontaine’s dominant autosomal syndrome (ectrodactyly and syndactyly involving the feet, cleft palate, micrognathia, dysplasic outer ear and, in some cases, mental retardation), ADULT (Acro- Dermato-Ungual-Lacrimal-Tooth) syndrome (ectrodactyly, hypodontia, premature loss of permanent teeth, lacrimal duct obstruction, onychodysplasia, and pigmentary lesions), Apert’s syndrome (craniosynostosis, hypertelorism, and pincer hand), and ectrodactyly with central polydactyly.
In the past, ectrodactyly could be detected only at birth by physical examination. Currently, this condition can be prenatally diagnosed by ultrasound, even in the first half of pregnancy [4]. Therefore, fetuses at risk should be examined as early as possible combining transabdominal and transvaginal routes. Early examination can relieve parents’ anxiety and psychological stress associated with a long wait. Further, early diagnosis gives the parents a chance to terminate the pregnancy in compliance with legal regulations. While patients with ectrodactyly can currently benefit from corrective surgery, many parents think that negative impact due to disability, physical and emotional problems and lack of self- esteem is an excessive burden. These arguments lead the parents to decide the termination of the pregnancy when this condition is prenatally diagnosed. Thus, genetic counselling is the key to prevention. Lifelong prognosis is good for children born with isolated ectrodactyly. Limb function will vary with the severity of the defect present at birth. The newborn with ectrodactyly should be thoroughly evaluated by a multidisciplinary team with the participation of the geneticist, neonatologist, and plastic surgeon. Plastic and reconstructive operations of all defects causing functional impairment is mandatory. Web deepening may be performed alone or in addition to tissue augmentation [9]. New breakthroughs in the knowledge of ectrodactyly will no doubt promote better community integration for these patients.
References
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J. ARBUS1, A. GALINDO1, J.M. PUENTE1, M. GARCA VEGA1, M. HERNNDEZ2, & P. DE LA FUENTE1
1 Ultrasound and Fetal Physiopathology Unit, Department of Obstetrics and Gynecology, Hospital Universit\ario “12 de Octubre”, Madrid, and 2 Department of Pathology, Hospital Universitario “12 de Octubre”, Madrid, Spain
Correspondence: J. Arbus, Department of Obstetrics and Gynecology, Hospital Universitario “12 de Octubre”, Avenida de Crdoba s/no, Madrid 28041, Spain. Tel: 034 1 3908310, Fax: 34 1 3908376. E-mail: [email protected]
Copyright CRC Press Apr 2005
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