Dorobek Małgorzata, van der Maarel Silvère M, Lemmers Richard J L F, Ryniewicz Barbara, Kabzińska Dagmara, Frants Rune R, Gawel Malgorzata, Walecki Jerzy, Hausmanowa-Petrusewicz Irena
Department of Neurology, Central Clinical Hospital of the Ministry of Interior, Warsaw, Poland Neuromuscular Unit, Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland.
Leiden University Medical Center, Center for Human and Clinical Genetics, Leiden, the Netherlands.
J Child Neurol. 2015 Apr;30(5):580-7. doi: 10.1177/0883073814528281. Epub 2014 Apr 9.
Facioscapulohumeral muscular dystrophy cases with facial weakness before the age of 5 and signs of shoulder weakness by the age of 10 are defined as early onset. Contraction of the D4Z4 repeat on chromosome 4q35 is causally related to facioscapulohumeral muscular dystrophy type 1, and the residual size of the D4Z4 repeat shows a roughly inverse correlation with the severity of the disease. Contraction of the D4Z4 repeat on chromosome 4q35 is believed to induce a local change in chromatin structure and consequent transcriptional deregulation of 4qter genes. We present early-onset cases in the Polish population that amounted to 21% of our total population with facioscapulohumeral muscular dystrophy. More than 27% of them presented with severe phenotypes (wheelchair dependency). The residual D4Z4 repeat sizes ranged from 1 to 4 units. In addition, even within early-onset facioscapulohumeral muscular dystrophy type 1 phenotypes, some cases had uncommon features (head drop, early disabling contractures, progressive ptosis, and respiratory insufficiency and cardiomyopathy).
面肩肱型肌营养不良症患者在5岁前出现面部无力，10岁前出现肩部无力体征被定义为早发型。4号染色体长臂35区（4q35）上D4Z4重复序列的收缩与1型面肩肱型肌营养不良症病因相关，且D4Z4重复序列的剩余大小与疾病严重程度大致呈负相关。4号染色体长臂35区（4q35）上D4Z4重复序列的收缩被认为会引起染色质结构的局部变化，进而导致4q末端基因转录失调。我们展示了波兰人群中的早发型病例，这些病例占我们所有面肩肱型肌营养不良症患者总数的21%。其中超过27%表现出严重的表型（依赖轮椅）。D4Z4重复序列的剩余大小范围为1至4个单位。此外，即使在早发型1型面肩肱型肌营养不良症表型中，一些病例也有不常见的特征（头部下垂、早期致残性挛缩、进行性上睑下垂、呼吸功能不全和心肌病）。
