Rajab Anna, Kornak U, Budde B S, Hoffmann K, Jaeken J, Nürnberg P, Mundlos S
Genetic Unit, DGHA, Ministry of Health, Muscat, Sultanate of Oman.
Am J Med Genet A. 2008 Apr 15;146A(8):965-76. doi: 10.1002/ajmg.a.32143.
Excessive skin wrinkling and cutis laxa are seen in many genetic conditions and overlapping features can make a clinical diagnosis difficult. Here we report on 22 Omani patients from 11 consanguineous families with the diagnosis of wrinkly skin syndrome (WSS, OMIM 278250) or geroderma osteodysplasticum hereditaria (GO, OMIM 231070). The WSS phenotype evolves during early childhood and includes a generalized and excessive skin wrinkling, dental problems, herniae, foot deformities, hip dislocations, growth retardation, and a large anterior fontanelle. The facial gestalt is characterized by a broad nasal bridge, hypertelorism, and downslanting palpebral fissures. We were unable to differentiate between WSS and cutis laxa with growth and developmental delay (CLGDD, OMIM 219200) suggesting that both can be considered as one entity. Distinct hallmarks of GO were skin wrinkling limited to the dorsum of hands and feet and to the abdomen, normal fontanelles, maxillary hypoplasia, bowed long bones, and osteopenia with frequent fractures. In contrast to the attenuation of the skin phenotype with age in WSS, adult patients with GO appeared prematurely aged. A serum sialotransferrin type 2 pattern was found in all four WSS patients tested. Apolipoprotein CIII (a marker for O-glycosylation) was normal suggesting that WSS is frequently associated with a N-protein glycosylation defect, probably at the level of processing (CDG-II). All four investigated GO patients showed normal sialotransferrin patterns. The known loci for cutis laxa and WSS on 2q31, 5q23-q31, 7q11, 11q13, and 14q32 were excluded. We suggest that WSS and GO are distinct entities with overlapping features.
在许多遗传疾病中都可见到皮肤过度褶皱和皮肤松弛，且重叠的特征可能使临床诊断变得困难。在此，我们报告了来自11个近亲家庭的22名阿曼患者，他们被诊断为皱纹皮肤综合征（WSS，OMIM 278250）或遗传性骨发育不良性老年皮病（GO，OMIM 231070）。WSS表型在儿童早期出现，包括全身性和过度的皮肤褶皱、牙齿问题、疝气、足部畸形、髋关节脱位、生长发育迟缓以及前囟门大。面部形态特征为鼻梁宽、眼距过宽和睑裂下斜。我们无法区分WSS和伴有生长发育迟缓的皮肤松弛（CLGDD，OMIM 219200），这表明两者可被视为同一实体。GO的明显特征是皮肤褶皱仅限于手背部、足部和腹部，囟门正常，上颌骨发育不全，长骨弯曲以及骨质减少且频繁骨折。与WSS中随年龄增长皮肤表型减弱不同，成年GO患者显得过早衰老。在所有检测的4名WSS患者中发现了血清2型唾液酸转铁蛋白模式。载脂蛋白CIII（O-糖基化的标志物）正常，这表明WSS通常与N-蛋白糖基化缺陷相关，可能在加工水平（先天性糖基化障碍-II型）。所有4名接受调查的GO患者唾液酸转铁蛋白模式均正常。排除了已知的位于2q31、5q23 - q31、7q11、11q13和14q32的皮肤松弛和WSS的基因座。我们认为WSS和GO是具有重叠特征的不同实体。
