To date, the diagnosis of FSHD was usually made on the basis of clinical findings in Korea. Although individual patients with FSHD may vary to some extent, most of the patients fit into a clinically typical feature. However, with the availability of genetic testing, it has been recently reported that the clinical manifestations of FSHD are much broader than previously known (6
). Therefore, it can be misleading to make a diagnosis solely based on the clinical findings especially in the patient with atypical presentations. In our study, two patients showed unusual clinical features. The initial diagnosis of patient 3 was idiopathic brachial plexopathy due to right arm weakness, asymmetric winged scapulae, and a negative family history. In patient 4, facial weakness and family history were absent. Furthermore, other tests including serum CK, needle electromyography, and muscle biopsy often do not helpful in the diagnosis of FSHD, as in our patients. Therefore, genetic testing is essential to confirm the correct diagnosis of FSHD. And it will be also helpful to facilitate the diagnosis and avoid unnecessary tests, especially in the patient with atypical presentations.
Molecular diagnosis for FSHD is used for diagnostic confirmation, pre-symptomatic testing, and for prenatal diagnosis. FSHD diagnosis relies on the detection of a D4Z4 repeat array less than 35 kb (<10 units) (20
). However, a number of factors have complicated the molecular diagnosis of FSHD (13
). First, it was reported that a highly homologous and equally polymorphic repeat resides on chromosome 10. Second, in nearly one-fifth of all individuals, exchanges of repeat units have been observed between chromosomes 4 and 10. A third complication comes from the observation of a biallelic variation of chromosome 4qter, designated 4qA and 4qB. It is reported that FSHD is associated solely with the 4qA allele and contractions of D4Z4 on 4qB subtelomeres do not cause FSHD (21
). Furthermore, a minority of patients carries a contraction of D4Z4 that extends in a proximal direction. The disease allele in these patients often goes undetected, as the probe region is also missing from the disease allele. Lastly, locus heterogeneity still remains. Nonetheless, Southern blot analysis using two restriction enzymes discriminating 4-type and 10-type units are very useful that FSHD can be diagnosed with up to 98% accuracy (23
Recently, a new diagnostic method for rapid and specific diagnosis of FSHD by a long PCR has been introduced (19
). This long PCR method can specifically amplify the repeated region from chromosome 4q up to 18.4 Kb in size and countable from one to five D4Z4 repeated units. By using this new technique, we can confirm a diagnosis of FSHD in one patient in whom we could not perform conventional Southern blot analysis due to insufficient DNA. Although Lemmers et al. (24
) argued that at least half of the Caucasian FSHD patients could not be diagnosed by the long PCR method because of the different distribution of D4Z4 repeats alleles in Japanese and in Caucasians, this method might be useful when the conventional Southern blot analysis is unavailable. Nevertheless, careful attention should be made to prevent false-negative results by long PCR method because of amplification failure due to 5 or more D4Z4 repeats.
Penetrance of FSHD was found variable by age and gender that it was 83% by age 30 yr and males were reported to be more severely and more frequently affected than females (95% vs. 69%, respectively) (25
). Anticipation in FSHD remains controversial, but an inverse correlation between D4Z4 repeat size and the clinical severity and onset age was reported (4
). A similar result was suggested only in the clinical severity in our study. However, the number of the patients in our study was too limited to clearly verify a relationship between the clinical features and D4Z4 repeat size. Further study in a larger number of the FSHD patients is needed.
This study reports four patients with genetically established FSHD. Two of them had family histories while the others did not. Considering that genomic structure of D4Z4 repeat in chromosomes 4 and 10 in Koreans is similar to that in Japanese, the frequency of FSHD might not be different from that in Japan (26
). However, there are only limited reports on the FSHD in Korea (14
). Therefore, more efforts should be made to identify and to diagnose Korean patients with FSHD by genetic analysis