Balkan Journal of Medical Genetics

MYOTONIC DYSTROPHY-2: UNUSUAL PHENOTYPE DUE TO A SMALL CCTG-EXPANSION
Finsterer J, Stöllberger C, Reining-Festa A, Loewe-Grgurin M, Gencik M
*Corresponding Author: Josef Finsterer, M.D., Ph.D., Krankenanstalt Rudolfstiftung, Messerli Institute, Veterinary University of Vienna, Postfach 20, 1180 Vienna, Austria. Tel. +43-1-71165-92085. Fax. +43-1-4781711. E-mail: fifigs1@yahoo.de
page: 39

DISCUSSION

The presented patient is noteworthy for a number of aspects. First, the clinical presentation is distinct from previously reported phenotypes (Table 1). Not reported so far were thrombocytosis, hyperuricemia, vesico-urinary reflux, hydronephrosis, gallstones, hyperlipidemia, and arterial hypertension (Table 1). Whether these features were truly due to the CCTG-repeat expansion, remains speculative and requires further investigation. Thrombocytosis and hyperuricemia have not been reported in association with MD1 either. Heterozygosity of the FVL mutation has not been reported as a manifestation of MD2. Only in a single patient with MD1 has such an association been reported [2]. Second, disregarding the vesico-ureteral reflux, the patient remained asymptomatic during a period of at least 20 years since detection of hyper-CKemia. The patient developed the first symptoms attributable to MD2 not earlier than at age 51 years. She had asymptomatic hyper-CKemia during years without developing muscle symptoms. Clinical muscle manifestations (exercise-induced weakness, myotonia) occurred not earlier than age 51 years, 20 years after first recognition of hyper-CKemia. Though obese, the patient did not complain about easy fatigability or exercise intolerance. Third, the patient developed a melanoma and dysplasias of the cervix uteri. Whether the risk of developing a neoplasm is increased in MD2 is under debate [3]. However, melanoma has been repeatedly reported in patients with MD1 [4]. There are also indications that MD1 predisposes for the development of basal cell carcinoma [5]. Though melanoma has not been reported in MD2, there is generally, both in MD1 and MD2, an increased risk of premature ageing and impaired vitamin-D homeostasis [6]. In accordance with these findings, the presented patient had vitamin-D deficiency as well. In a study of 307 patients with myotonic dystrophy, without specifying how many had MD1 or MD2, it was concluded that these patients carry an increased risk of developing thyroid cancer, melanoma, testicular carcinoma, and prostate carcinoma [7]. The mechanism underlying the association is unclear, but it can be speculated that impaired protein production due to the RNA defect, may generally lead to cell dysfunctions at multiple levels, including cell division and oncogenesis. Whether thrombocytosis reflects the increased risk of neoplasms remains speculative. Fourth, the patient had hydroureter, ovarian cysts, and renal cysts. A hydroureter or hydronephrosis has not been previously reported in association with MD1 or MD2 [8]. Despite extensive work-up for the cause of hydroureter, the cause remained undetermined. Renal cysts have not been reported in association with MD1 or MD2 either but pancreatic cysts have rarely been observed [9]. Ovarian cysts have been rarely reported in MD1 [10] but not in MD2. In conclusion, this case shows that asymptomatic hyper-CKemia in association with diabetes, gallstones, hyperlipidemia, hyperuricemia, renal cysts, hydroureter, arterial hypertension, and thrombocytosis should raise the suspicion of an MD2. In patients with asymptomatic hyper-CKemia needle-EMG should be considered to look for myotonic and pseudomyotonic discharges. Myotonic dystrophy type 2 may take a mild course over many years if the CCTG-expansion is short.

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