Jezela-Stanek Aleksandra, Kucharczyk Marzena, Falana Katarzyna, Jurkiewicz Dorota, Mlynek Marlena, Wicher Dorota, Rydzanicz Malgorzata, Kugaudo Monika, Cieslikowska Agata, Ciara Elzbieta, Ploski Rafal, Krajewska-Walasek Malgorzata
Department of Medical Genetics, The Children's Memorial Health Institute, Warsaw, Poland.
Department of Medical Genetics, Warsaw Medical University, Warsaw, Poland.
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2016 Mar;160(1):161-7. doi: 10.5507/bp.2016.006. Epub 2016 Feb 29.
Sotos syndrome 2 (MIM #614753), known also as Malan syndrome, is caused by heterozygous mutations/deletions of the NFIX gene located on chromosome 19p13.2. It manifests in developmental delay, intellectual impairment, macrocephaly, central nervous system anomalies, postnatal overgrowth, and craniofacial dysmorphism. Unusual behavior with/without autistic traits, ophthalmologic, gastrointestinal, musculo-skeletal, and hand/foot abnormalities are also frequent. Due to the limited number of such cases, no definitive conclusions about genotype-phenotype correlations have been possible. In the following paper, we discuss physical features consistent with Sotos syndrome 2 based on literature review and two new cases [a patient with de novo 19p13.2 deletion encompassing a part of the NFIX gene and a patient with de novo (not described so far) heterozygous missense mutation c.367C>T (p.Arg123Trp) in the NFIX gene].
Apart from overgrowth and psychomotor developmental delay, the most consistent physical features of our two patients are dysmorphism including high forehead, downslanting palpebral fissures, pointed chin, and abnormalities of the pinna. Both show abnormal behavior and present with long, tapered fingers and toenail defect. No severe congenital malformations were noted.
We hope these data will serve as a material for further studies and provide an opportunity to make more reliable genotype-phenotype correlations.
索托斯综合征2型（MIM #614753），也称为马兰综合征，由位于19号染色体p13.2区域的NFIX基因杂合突变/缺失引起。其表现为发育迟缓、智力障碍、巨头畸形、中枢神经系统异常、出生后过度生长以及颅面畸形。伴有或不伴有自闭症特征的异常行为、眼科、胃肠道、肌肉骨骼以及手足异常也较为常见。由于此类病例数量有限，关于基因型与表型相关性尚未得出明确结论。在接下来的论文中，我们基于文献综述以及两例新病例[一例为新发19p13.2缺失累及部分NFIX基因的患者，另一例为新发（迄今未描述）NFIX基因杂合错义突变c.367C>T（p.Arg123Trp）的患者]，讨论与索托斯综合征2型相符的身体特征。
除了过度生长和精神运动发育迟缓外，我们这两名患者最一致的身体特征是畸形，包括额头高、睑裂向下倾斜、下巴尖以及耳廓异常。两人均表现出异常行为，且手指和脚趾细长、指甲有缺陷。未发现严重的先天性畸形。
我们希望这些数据能作为进一步研究的素材，并提供机会以建立更可靠的基因型与表型相关性。
