Pediatrics Department, Miguel Servet Children's Hospital, Isabel la Católica Avenue 1-3, 50009, Zaragoza, Spain.
Clinical Genetics and Assisted Reproduction, Clinical Biochemistry Department, Miguel Servet Hospital, Padre Arrupe Street, 50009, Zaragoza, Spain.
BMC Pediatr. 2019 Apr 5;19(1):92. doi: 10.1186/s12887-019-1463-1.
Rasopathies are a group of genetic malformative syndromes including neurofibromatosis 1, Noonan, LEOPARD, Costello, cardio-facio-cutaneous, Legius, and capillary malformation-arteriovenous malformation syndromes.
We present a female newborn that consulted at the emergency department with refusal to eat and sleepiness. A shortened femur, thickened nucal fold and suspect for agenesis of the corpus callosum were observed in prenatal ultrasound. Her phenotype included hypertelorism, antimongoloid obliquity of the palpebral fissure, prominent forehead, long filtrum, thickened nucal fold, separated nipples, widespread thickened skinfolds and café-au-lait spots. She had a systolic murmur due to pulmonary valve stenosis. The NF1 gene testing found the pathogenic variant p.E2586X (c.7756G > T) in exon 53, not described in any international database or scientific publications yet. Also, a mutation in the Kras gene was detected (p.Val14lle), which is associated with mild Noonan phenotype. Both variations were de novo.
Not all genes and mutations have already been discovered, so it's important to document new findings, like our patient's, to enrich and update the international database and broaden all possible knowledge about rasopathies. This is the first case to be described presenting simultaneously two mutations in Kras and NF1 genes, whose possible synergic effect regarding its pathogenicity is unknown, but could be interesting towards therapeutic alternatives.
Ras 病是一组遗传性畸形综合征，包括神经纤维瘤病 1 型、Noonan 综合征、LEOPARD 综合征、Costello 综合征、心面 cuts 综合征、Legius 综合征和毛细血管畸形-动静脉畸形综合征。
我们介绍了一位女性新生儿，因拒食和嗜睡到急诊科就诊。产前超声检查发现股骨缩短、颈后皮肤皱褶增厚，疑为胼胝体发育不全。她的表型包括眼距过宽、内眦赘皮、前额突出、长睑裂、颈后皮肤皱褶增厚、乳头分开、广泛的皮肤褶皱增厚和咖啡牛奶斑。她有肺动脉瓣狭窄引起的收缩期杂音。NF1 基因检测发现 53 号外显子的致病性变异 p.E2586X（c.7756G>T），尚未在任何国际数据库或科学出版物中描述。此外，还检测到 Kras 基因的突变（p.Val14lle），与轻度 Noonan 表型相关。这两种变异均为新生突变。
并非所有基因和突变都已被发现，因此记录新的发现（如我们患者的情况）非常重要，以丰富和更新国际数据库，并扩大对 Ras 病的所有可能的了解。这是首例同时存在 Kras 和 NF1 基因突变的病例，其致病性的可能协同作用尚不清楚，但可能对治疗选择具有重要意义。
