Case report Klin~felter's syndrome 48,XXYY Refracto,y leg ulcers in a patient with 43~ ararevarla,nt ef Klinefelters syndrome S. Lauchli, J . Hafner and G. Burg SUMMARY A case of a 17-year old boy with extensive ulcers on both lower legs is presented. Clinical examination showed an unusually tall stature, obesity and eunuchoid habitus. Chromosomal analysis revealed a karyotype of 48,XXYY, a rare variant of Klinefelter's syndrome (47,XXY). After treatment with moist gauze and many recurrences, rapid ulcer healing could be achieved with topical application of Factor XIII. Patients with 48,XXYY seem to be particularly prone to developing extensive leg ulcers. Possible etiolo- gies include chronic venous insufficiency and microvascular disturbances as a consequence of fibrin- olytic abnormalities. Differences between Klinefelter's syndrome (47,XXY) and 48,XXYY are discussed. Introduction Klinefelter's syndrome is one of the most common chromosomal variations in humans. Patients with this syndrome have at least one extra X chromosome which results in a karyotype of 47,XXY or, in less common variations, 48,XXXY, 49,XXXXY andXY/XXY mosaic (1). One rare variant is the 48,XXYY syndrome (2). Boys with the latter syndrome are, like Klinefelter patients, usually of a tall stature with a eunuchoid habitus and small testes. There are, however also some important clifferences: more often than in Klinefelter syndrome, patients with a 48,XXYY ka1yotype show cognitive or behavioral problems and extensive ulcers of the lower limbs (3). Patients with a female phenotype ancl extra X chromosomes can have a karyotype of 47,XXX and usu- ally show very little, if any, clinical abnormalities, which might include tall sta ture and neuromotor developmen- tal clelay, but normal sexual clevelopment. Case report A 17 year-olcl boy was seen at our clinic for the first tirne in 1995 with extensive ulcers on both legs, which hacl persistecl in spite of intensive therapy. His family history was unremarkable for genetic cliseases. He had just started an apprenticeship as a cook, a job which involved long periods of standing. Initial examination Acta Dermatoven APA Vol 11, 2002, No 4 ------------- -----J29 Klinefelter's syndrome 48,XXYY Figure1. Patient with XXYY-syndrome featuring tall stature, eunuchoid habitus and gynecomastia revealed an unusually tall , obese boy with gynecomas- tia and hypoplastic testes (Figure 1). Both legs presented with ulcerations on the medial and fronta! aspect ofthe shin (Figure 2) as well as the dorsum of the left foot (Figure 3a). The ulcerations measured up to 6 cm in diameter and were covered with large quantities of fi- brinous exsudate. There were no conspicuous varicose Figure 2. Heavily exsuding pHeaHHh retibial ulcer of patient with XXYY-syndrome veins and the dorsal arteries of both feet w ere easily palpable. Blood work showed normal results. In par- ticular, there were no signs of a coagulation disorder, all the parameters including thrombocytes, antithrom- bin III, Plasminogen, Protein C and S w ere all within the normal range. The patient was treated in our outpatient clinic with Figures 3 a and b. Ulcer of the left forefoot before and after treatment with topical Factor XIII Case report 130 - - --------- ------- - --------------Acta Dermatoven APA Vol 11, 2002, No 4 Case report compression therapy and moist gauze dressing, which resulted in complete healing after several months, only to recur a few weeks later. In the fallowing year, insuf- ficiency of both greater saphenous veins could be de- tected by means of duplex sonography. After stripping of both greater saphenous veins, the ulcers healed far more than one year, but severa! recurrences fallowed. In 2001, the patient was readmitted to our clinic with ulcers that had persisted far more than one year. This tirne, almost complete healing could be achieved within two months with application of topical factor XIII (Fibrogammin a) in addition to moist, non-adherent wound dressings and compression therapy (Figure 3b). Discussion In the early 1940's, Hany Klinefelter was a trave]jng fel- / low at Harvard Medica! School in Boston, Mass., where he worked in the endocrinology laboratory. After he broke severa! pieces of expensive equipment in the laboratory, he was transferred to another department that did not require laboratory work. There, in the group of Dr. Fuller Albright at Massachusetts General Hospi- tal, he hacl the opportunity to fallow a large number of patients. He noticed severa! unusually tali boys with gynecomastia, small testes and elevated levels of gona- clotropin releasing hormone (GnRH) as well as Follicle- Stimulating Hormone (FSH) ancl lutenizing hormone (LH). This led to the first publication describing this syn- drome subsequently namecl after Hany Klinefelter ( 4). While it is now generally accepted that the 48,XXYY synclrome is a variant of Klinefelter syndrome, many authors stress the importance of differentiating between the two (3, 5). Both entities can be traced to a common pathogenetic mechanism, i.e . they can be consiclerecl a consequence of meiotic non-clisjunction cluring sper- matogenesis or oogenesis (2). Because Klinefelter's syn- drome is a sexual clisorder, its specific features are usu- ally not noticed in individuals until they reach puberty. Boys with Klinefelter's synclrome often show ve1y dis- crete clinical features, including tali stature, obesity, gynecomastia and eunuchoid habitus, therefare the syndrome is often not diagnosed. These features are shared by patients with all variations of Klinefelter's syndrome. In addition, they have small testes, a normal to low testosterone leve! and are infertile. Although l y E li'E, R E· l'