1 Department of Obstetrics and Gynecology, University of Bonn School of Medicine, Bonn, and 2 Division of Cardiology, Department of Internal Medicine, University of Bonn School of Medicine, Bonn, Germany
3 To whom correspondence should be addressed at: Department of Obstetrics and Gynecology, University of Cologne School of Medicine, Kerpener Str. 34, D-50931 Cologne, Germany. e-mail: UweAUlrich{at}AOL.com
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Abstract |
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Key words: hearthand syndrome/HoltOram syndrome/Mayervon RokitanskyKüsterHauser syndrome/neovagina/Vecchiettis technique
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Introduction |
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HoltOram syndrome (HOS), also referred to as hearthand syndrome, is characterized by congenital heart abnormalities and skeletal malformations of the upper limb, ranging from subtle changes, such as hypoplasia or absence of the thumb (Fakih et al., 1987), to frank phocomelia, with the left side usually being more severly affected (Holt and Oram, 1960
; Smith et al., 1979
; Bossert et al., 2002
). It is a monogenic disorder, inherited in an autosomal dominant trait with complete penetrance and variable expression in the affected families (Basson et al., 1997
). The HOS gene is mapped to the long arm of chromosome 12 (12q24.1) and encodes a T-box-containing transcription factor (TBX5). An analysis of the variable expressivity of HOS by mutation screening in 55 subjects with HOS suggests that neither the type of mutation in TBX5 nor the location of a mutation in the T-box is predictive of the expressivity of malformations in individuals with HOS (Brassington et al., 2003
). Despite the autosomal dominant inheritance of HOS, females are predominantly and more severely affected (Newbury-Ecob et al., 1996
). The most common cardiac defects associated with HOS are ostium secundum atrial septum defect (in
60% of the cases), followed by ostium primum atrial septum defect and ventricular septum defect (Sletten and Pierpont, 1996
). However, a wide variety of complex cardiac anomalies may occur in HOS, such as mitral valve prolapse, tetralogy of Fallot, hypoplastic left heart syndrome and tricuspid atresia (Zhang et al., 1986
; Glauser et al., 1989
; Lehner et al., 1994
; Bossert et al., 2002
). These anomalies may be accompanied by a variety of supraventricular and ventricular electrocardiogram (ECG) abnormalities, consisting of conduction or pacemaker disturbances up to complex arrhythmia (Zhang et al., 1986
). In addition, anatomical anomalies of the large vessels have been reported, including patent ductus arteriosus, hypoplastic pulmonary artery and persistent left superior vena cava (Massumi and Nutter, 1966
; Solit et al., 1973
). An aorto-pulmonary window (APW) is a rare cardiac malformation and was first described by Elliotson (1830
). In 90% of patients, it consists of a large oval defect between the ascending aorta and the pulmonary trunk. The APW normally should be closed either by surgical or by interventional techniques (i.e. umbrella closure) before irreversible changes of the pulmonary vessels develop (Tulloh and Rigby, 1997
). Hitherto, and to the best of our knowledge, APW has not been described in association with HOS (MEDLINE/PubMed search).
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Case report |
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Upon presentation, the patient was 1.54 m tall and weighed 47 kg. On physical examination, musculo-skeletal disorders were noticed as follows: scoliosis of the lumbar spine and weakness of the M.trapezius, M.deltoideus and Mm.biceps and triceps. Abduction and opposition of the right thumb, which was in the same plane as the fingers, were impaired. She also had hypoplasia of the left humerus with absence of radius and ulna (phocomelia, Figure 1). Her breast development was normal, Tanner 5, as was that of her pubic hair and her external genitalia. Instead of a normal vagina there was a small pouch 2 cm in length (Figure 2). Rectal palpation failed to detect a uterus, which was confirmed on transabdominal ultrasound examination. There was a normal female karyotype, 46,XX. Laboratory testing demonstrated normal levels of estradiol, testosterone and FSH.
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The psychosexual identity of the patient is clearly female. She has a partner, and the impossibility of having sexual intercourse caused her great problems. After detailed information about the different options for creating a neovagina, the patient decided to undergo laparoscopic creation of a neovagina by the modified Vecchietti method. Intra operatively, rudimentary uterine horns were identified adjacent to the morphologically normal ovaries which were located at the pelvic side walls. Surgery and the post-operative course were uneventful, resulting in a neovagina 10 cm in length.
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Discussion |
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There are other hereditary and sporadic complex malformation syndromes concerning Müllerian anomalies, renal, heart and skeletal malformations that have been classified and separated from classical MRKHS, e.g. KlippelFeil syndrome (KFS), MURCS association and VACTERL association. KFS was traditionally defined by the classic triad of short neck, low posterior hairline and restriction of neck movement due to segmentation failure of the cervical vertebrae (Scott, 1993). The original definition of three types of KFS by Feil has been replaced by a new classification by Clarke. This classification is based on the inheritance and the most rostral vertebral fusion diagnosed (Clarke et al., 1998
). Other anomalies that are typical of KFS, such as spina bifida, Sprengel anomaly (30%) and deafness (30%), are not common in MRKHS. However, a unique family with KFS has been reported with hypoplasia of the thumb, one of the characteristic anomalies in MRKHS (Hensinger et al., 1974
). The VACTERL association includes vertebral anomalies, cardiac and renal malformations and limb anomalies. The MURCS association is a combination of Müllerian duct aplasia, renal aplasia and cervicothoracic somite dysplasia. These syndromes are rare.
The absence of the vagina is a huge problem for the affected women. This diagnosis not only means infertility but also makes it impossible to have satisfactory vaginal intercourse. The laparoscopic creation of a neovagina by the modified Vecchietti technique is simple, safe and effective, with good functional results (Keckstein et al., 1995). In addition, having MRKHS and HOS may cause serious psychosexual and psychosocial problems. Therefore, sound knowledge concerning options as well as the limits of different therapeutic interventions is essential when counselling such patients. Psychological and social support is also needed. The large number of associated disorders of MRKHS and HOS is an interdisciplinary challenge facing cardiologists, cardiovascular and orthopaedic surgeons, and gynaecologists.
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Acknowledgement |
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References |
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Submitted on October 27, 2003; accepted on February 5, 2004.
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