Objective:To analyze and summarize the clinical and genetic features of Noonan syndrome (NS) caused by mutations in the leucine zipper-like transcription regulator 1 ( LZTR1) gene. Methods:The retrospective study analyzed a patient who was examined at the Center of Prenatal and Hereditary Disease Diagnosis, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University in January 2021 because of fetal nuchal translucency thickening and a previous history of problematic pregnancies. Subsequently, the patient was diagnosed with Noonan syndrome (NS) through whole exome sequencing. Using keywords such as "Noonan syndrome," "Leucine zipper-like transcription regulator 1", and " LZTR1", clinical and genetic characteristics of NS derived from LZTR1 mutations were summarized by extracting relevant literature from China National Knowledge Infrastructure, Wanfang Database, Yiigle, PubMed and Web of Science, covering from January 2013 to October 2022. Descriptive analysis was applied to the data. Results:(1) Case report: WES and Sanger sequencing showed the existence of the biallelic variants of LZTR1 gene c.842C>T and c.2248G>A in the fetus (Ⅱ-3) and the proband (Ⅱ-2) that inherited from the father and the mother, respectively. Based on the typical special facial appearance and short stature in the proband indicative of NS, the fetus and the proband were diagnosed with autosomal recessive inheritance (AR) NS. The pregnant woman terminated her pregnancy at 22 weeks due to severe edema of the fetus. At the age of three, the proband exhibited typical craniofacial features and short stature characteristics of NS when presented to our hospital. The proband received regular follow-ups in the pediatrics department of other hospitals, where recombinant human growth hormone was used to improve his height. He attended kindergarten at age four and can communicate and play with other children normally. (2) Literature review: 95 cases of NS associated with LZTR1 mutations have been retrieved and included. When including the fetus and the proband of this case, the total reached 97 cases, involving 79 different mutation sites. Forty-three cases (44.3%) were AR, and 54 (55.7%) were autosomal dominant inheritance (AD). Missense mutation was the most prevalent type of mutation, whereas nonsense mutation and frameshift mutation were more common in biallelic variants. Across all cases, the clinical manifestations encompassed multiple systems, primarily characterized by craniofacial dysmorphia, skeletal deformities, heart defects, and short stature. Developmental delay, learning disabilities, and mental retardation of varying degrees may accompany these symptoms. Eighteen cases described antenatal phenotypes, with 16 of them reporting biallelic AR variants. Ultrasound findings of 18 prenatal cases revealed 11 cases of fetal NT thickening, seven cases of cystic hygroma, four cases of fetal pericardium or pleural effusion, two cases of severe fetal edema, and 11 cases of cardiovascular defects. Conclusions:NS induced by LZTR1 mutations is an autosomal dominant or recessive inherited genetic syndrome with a broad spectrum of clinical phenotypes. The severity of the disease varies among children with the same genotype. NS should be considered when prenatal ultrasound indicates nonspecific manifestations, such as fetal NT thickening, cervical lymphatic hydrops, polyhydramnios, fetal edema, and congenital heart defects. Prenatal identification is crucial for evaluating the prognosis of children and assisting families in making clinical decisions.

Objective     To investigate the combined effects of digastric muscle low frequency modulated medium frequency electro-acupuncture therapy and voice training for dysphagia in patients who underwent aortic arch surgery. Methods     Forty-two consecutive patients with dysphagia after aortic arch surgery between October 2014 and November 2017 were divided into two groups including an observation group and a control group. There were 21 patients in each group. There were 17 males and 4 females at age of 51.0±6.5 years in the observation group, while 18 males and 3 females at age of 49.8±7.3 years in the control group. The patients in the observation group underwent electroacupuncture therapy and voice training (20 min per day for each therapy, 2 weeks), while the patients in the control group only received safe swallowing education and rehabilitation guidance (2 weeks). The test results, such as fibrolaryngoscope and functional oral intake scale (FOIS) score, and the data of computer phonatory detection, before and after the intervention were  compared. Results     The fibrolaryngoscope of vocal cords significantly decreased and the FOIS score significantly increased after digastric muscle low frequency modulated medium frequency electro-acupuncture therapy and voice training in the observation group(6.30 vs. 4.60, P<0.05). Bucking was obviously reduced. The indicators of hoarse degree, such as median pitch, fundamental frequency, jitter (0.60%±0.96% vs. 1.99%±1.86%, P=0.033), shimmer (2.47%±4.26% vs. 5.89%±3.66%, P=0.043), maximum phonation time (15.31±9.10 s vs. 3.72±8.83 s, P=0.006), maximum and loud phonation time (9.30±5.73 s vs. 2.32±2.99 s, P=0.039), mean noise-to-harmonics ratio (23.99±10.17 vs .9.98±9.37, P=0.006) and mean harmonics-to-noise ratio (0.03±0.02 vs. 0.17±0.23, P=0.019) improved after the treatment in both groups. But the improvement in the observation group was significantly better than that in the control group. Conclusion     The combination of digastric muscle low frequency modulated medium frequency electro-acupuncture therapy and voice training on dysphagia in patients who underwent aortic arch surgery can significantly improve the swallowing function of patients. Meanwhile, it also helps the recovery of phonic function and improves the ability of feeding and communication in these patients.