Kyphoscoliotic type of Ehlers-Danlos Syndrome (EDS VIA) in six Egyptian patients presenting with a homogeneous clinical phenotype
Kyphoscoliotic type of Ehlers-Danlos Syndrome (EDS VIA) in six Egyptian patients presenting with a homogeneous clinical phenotype
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DOI：
10.1007/s00431-014-2429-9
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发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Giunta, Cecilia
中科院分区：
文献类型：
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作者：
Abdalla, Ebtesam M.;Rohrbach, Marianne;Giunta, Cecilia
脊柱后凸型Ehlers-Danlos综合征（EDS VIA）是一种罕见的Recommendations遗传性结缔组织疾病，其特征是皮肤可擦伤、过度伸展、全身关节松弛、出生时严重肌肉张力减退和进行性先天性脊柱侧凸或脊柱后凸。由于PLOD 1突变导致赖氨酰羟化酶1（LH 1）缺乏导致胶原赖氨酰残基羟基化不足，因此导致胶原交联的异常形成。在这里，我们报告的临床，生化和分子研究结果在6个埃及患者从4个无关的家庭严重影响EDS VIA。除了经常报道的p.Glu326_Lys585dup之外，我们还鉴定了两种新的序列变体p.Gln208* 和p.Tyr675*，它们导致LH 1功能丧失或其缺陷。所有受影响的儿童都表现出类似的临床特征，此外，还有几个畸形的颅面特征，尚未在EDS VIA中描述。这些都是特定的每个家庭的受影响的个人，但在他们的父母和他们的未受影响的siblings.Conclusion：我们的描述6例患者提出了一个同质的临床表型和畸形颅面特征将有助于儿科医生在诊断这种罕见的疾病。
The kyphoscoliotic type of the Ehlers-Danlos syndrome (EDS VIA) is a rare recessively inherited connective tissue disorder characterized by bruisable, hyperextensible skin, generalized joint laxity, severe muscular hypotonia at birth and progressive congenital scoliosis or kyphosis. Deficiency of the enzyme lysyl hydroxylase 1 (LH1) due to mutations in PLOD1 results in underhydroxylation of collagen lysyl residues and, hence, in the abnormal formation of collagen cross-links. Here, we report on the clinical, biochemical, and molecular findings in six Egyptian patients from four unrelated families severely affected with EDS VIA. In addition to the frequently reported p.Glu326_Lys585dup, we identified two novel sequence variants p.Gln208* and p.Tyr675*, which lead either to loss of function of LH1 or to its deficiency. All affected children presented with similar clinical features of the disorder, and in addition, several dysmorphic craniofacial features, not yet described in EDS VIA. These were specific for the affected individuals of each family, but absent in their parents and their unaffected siblings.Conclusion: Our description of six patients presenting with a homogeneous clinical phenotype and dysmorphic craniofacial features will help pediatricians in the diagnosis of this rare disorder.