BACKGROUND: We report a pair of dichorionic diamniotic (DCDA) twin pregnancy affected by Noonan syndrome (NS) with a novel mutation of LZTR1 determined by genetic analysis.
METHODS: A pregnant woman with monozygotic twins (DCDA) at 12 + 2 weeks gestation was referred to our center. This was her second pregnancy following a previous delivery of a healthy infant. Nuchal translucency of two fetuses was 11.2 mm (CRL 62.0 mm) and 6.9 mm (CRL 62.1 mm) respectively. Ultrasound examination indicated cystic hygroma and hypoplastic ear. The couple was not consanguineous, and both had normal phenotype. Familial hereditary disease was also excluded. Under ultrasound guidance, 30 mg of chorionic villi was obtained for karyotyping, quantitative fluorescent polymerase chain reaction (QF-PCR), chromosomal microarray analysis(CMA), and Trio-whole-exome sequencing(WES) examination. We used the \"target region capture and sequencing\" for WES, and the BWA (Burrows Wheeler Aligner) Multi-Vision software package for the data analysis. The results of all these tests were normal except WES detected a c.427 A > G mutation in the exonic region of the LZTR1 gene and a p. Asn143Asp novel heterozygous mutation associated with NS in this pair of twins. In addition, WES suggested that the mutation in the twin fetuses originated from the mother. When the mother got the genetic test report, she came to our fetal medicine department for genetic counseling and she declined the appointment with a clinical geneticist. The couple opted to terminate the pregnancy. Because the patient did not choose to terminate the pregnancy at our hospital, we were unable to take further examination. With the help of colleagues in another hospital, photos of the fetuses were taken. Compared with the prenatal ultrasound results, the appearance of the \"cystic hygroma\" and \"hypoplastic ear\" was consistent with the ultrasound. The couple were depressed after knowing this pathogenic result and although we advised the mother to take further investigation, they refused.
CONCLUSIONS: The mutant locus might be incompletely dominant, which led to an abnormal fetal phenotype such as cystic hygroma and hypoplastic ear.

Genetic cardiac diseases are the main trigger of sudden cardiac death (SCD) in young adults. Hypertrophic cardiomyopathy (HCM) is the most prevalent cardiomyopathy and accounts for 0.5 to 1% of SCD cases per year.
Herein, we report a family with a marked history of SCD focusing on one SCD young adult case and one pediatric case with HCM.
For the deceased young adult, postmortem whole-exome sequencing (WES) revealed a missense variant in the ACTN2 gene: c.355G > A; p.(Ala119Thr) confirming the mixed hypertrophic/dilated cardiomyopathy phenotype detected in the autopsy. For the pediatric case, WES allowed us the identification of a novel frameshift variant in the LZTR1 gene: c.1745delT; p.(Val582Glyfs*10) which confirms a clinical suspicion of HCM related to Noonan syndrome.
The present study adds further evidence on the pathogenicity of ACTN2: p. Ala119Thr variant in SCD and expands the mutational spectrum of the LZTR1 gene related to Noonan syndrome.

In cases of fetal hydrops, searching for an etiology is essential to evaluate the fetal prognosis and propose the most appropriate management.