The genetic and clinical characteristics of oculopharyngeal muscular dystrophy patients in Israel.

backgroundOculopharyngeal muscular dystrophy (OPMD) is a late-onset autosomal dominant myopathy, caused by a (GCN)n/polyalanine repeat expansion in the PABPN1 gene. In Israel, OPMD is particularly prevalent among individuals of Jewish Bukharian descent due to a (GCN)13 repeat expansion. In this retrospective study, we collected genetic and clinical data of OPMD patients who visited the Israeli reference clinic from its opening in 2022 through September 2025 and were enrolled in the Israeli OPMD registry (IsrO-PMD).

resultsA total of 102 Jewish individuals with OPMD symptoms and a confirmed molecular diagnosis were identified (52 males, 51.0%). The heterozygous (GCN)13 repeat allele (10/13 genotype) was found in 95 patients (93.1%), of whom 89 (93.7%) were of Bukharian descent, five (5.6%) were of Bulgarian origin, and a single patient was from Georgia. In this 10/13 genotype group (n = 95), initial symptoms were dysphagia and ptosis, which occurred at a similar mean age of 53.0 ± 8.3 and 53.9 ± 7.2 years, respectively. Symptoms of limb muscle weakness occurred significantly later, at a mean age of 57.9 ± 10.2 years. Overall, the onset of symptoms occurred approximately 4 years earlier in females (48.9 ± 7.9, n = 48) than in males (52.6 ± 7.1, n = 47), and this difference was statistically significant (p = 0.02). However, the difference did not reach significance when calculated for each of the three symptoms separately. On evaluation, at a mean age of 61.6 ± 10.7 years, dysphagia was present in 92/95 (96.8%) of patients, ptosis in 85/95 (89.5%), and limb muscle weakness in 56/95 (58.9%) of cases, most notably of hip flexion and abduction. Different genotypes were detected in seven patients: Three of Bukharian descent were homozygous for (GCN)13 repeats, three of Karaite descent were homozygous for (GCN)11 repeats, and one of Tunisian origion was heterozygous for (GCN)15 repeats (10/15 genotype). DISCUSSION: While most OPMD patients in Israel are of Jewish Bukharian descent, patients from other origins were also identified. Dysphagia and ptosis are the common initial symptoms, and overall, the onset of symptoms was reportedly earlier in females. Proximal muscle weakness becomes common with disease progression. Further studies are required to delineate genotype-phenotype correlations.