Next Generation Sequencing Approach in a Prenatal Case of Cardio-Facio-Cutaneus Syndrome

Mucciolo, Mafalda; Russo, Claudio Dello; D’Emidio, Laura; Mesoraca, Alvaro; Giorlandino, Claudio

doi:10.3390/ijms17060952

Cited by 7 publications

(4 citation statements)

References 30 publications

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“…Prenatal Findings: increased NT was described once, caused by a pathogenic BRAF variant [Witters et al, 2008]. Cystic hygroma was found in 4 cases, caused by pathogenic variants in BRAF (n = 3) and MAP2K1 (n = 1) [Witters et al, 2008;Terry et al, 2014;Mucciolo 2016;Biard et al, 2019]. No pericardial and pleural effusions were described; 1 case showed ascites [Terry et al, 2014].…”

Section: Cardiofaciocutaneous Syndromementioning

confidence: 99%

Lymphatic Abnormalities in Noonan Syndrome Spectrum Disorders: A Systematic Review

Sleutjes¹,

Kleimeier²,

Leenders

et al. 2021

Mol Syndromol

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Noonan syndrome spectrum disorders are a group of phenotypically related conditions, resembling Noonan syndrome, caused by germline pathogenic variants in genes within the Ras/mitogen-activated protein kinase (Ras/MAPK) signalling pathway. Lymphatic dysplasia with a clinical lymphatic abnormality is one of the major features. We performed a systematic review to get more insight in (1) the prevalence of clinically lymphatic abnormalities in patients with a genetically proven Noonan syndrome spectrum disorder, (2) if a genotype-lymphatic phenotype relation can be found and describe the clinical presentation and course of the lymphatic abnormality. Most studies report patients with Noonan syndrome. Prenatally, the prevalence of increased nuchal translucency differs from 7% in patients with pathogenic PTPN11 variants to 38% in patients with pathogenic RIT1 variants, and the prevalence of pleural effusions differed from 7% in patients with pathogenic SOS1 to 29% in patients with pathogenic RIT1 variants. Postnatally, the prevalence of lymphedema differs from 16% in patients with pathogenic PTPN11 variants to 44% in patients with pathogenic SOS1 variants, and the prevalence of acquired chylothorax is 4% in patients with pathogenic RIT1 variants. Lymphatic abnormalities do occur in patients with cardiofaciocutaneous syndrome and Costello syndrome. In conclusion, Noonan syndrome spectrum disorders, Noonan syndrome in particular, are associated with lymphatic abnormalities. Combining the available published literature about genetically proven Noonan syndrome spectrum disorders, it appears likely that the lifetime prevalence of these abnormalities in Noonan syndrome is higher than the 20% that were generally accepted so far. This is increasingly important, because the activation of the RAS/MAPK pathway can be inhibited by RAS/MAPK inhibitors, and clinically severe lymphatic abnormalities may improve.

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Section: Cardiofaciocutaneous Syndromementioning

confidence: 99%

Lymphatic Abnormalities in Noonan Syndrome Spectrum Disorders: A Systematic Review

Sleutjes¹,

Kleimeier²,

Leenders

et al. 2021

Mol Syndromol

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“…Therefore, much of what is known about the natural history of CFC syndrome pertains to the postnatal phenotype. While several studies (Biard et al, 2019; Mucciolo et al, 2016; Myers et al, 2014; Scott et al, 2021; Sparks et al, 2020; Stuurman et al, 2019) have described prenatal features of the RASopathies in general, there remains a paucity of data pertaining to the prenatal features of CFC in particular. Thus, we sought to delineate the prenatal phenotype, and the obstetrical and neonatal outcomes, of pregnancies after which the child was confirmed to have CFC syndrome.…”

Section: Introductionmentioning

confidence: 99%

Obstetrical and neonatal outcomes of cardio‐facio‐cutaneous syndrome: Prenatal consequences of Ras/MAPK dysregulation

Jelin

Mahle

Tran

et al. 2022

American J of Med Genetics Pt A

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We systematically delineated the prenatal phenotype, and obstetrical and neonatal outcomes of the RASopathy cardio‐facio‐cutaneous (CFC) syndrome. A comprehensive, retrospective medical history survey was distributed to parents of children with confirmed CFC in collaboration with CFC International, Inc. Data were collected on CFC gene variant, maternal characteristics, pregnancy course, delivery, and neonatal outcomes with the support of medical records. We identified 43 individuals with pathogenic variants in BRAF (81%), MEK1 (14%), or MEK2 (5%) genes. The median age was 8.5 years. Hyperemesis gravidarum, gestational diabetes, gestational hypertension, and preeclampsia occurred in 5/43 (12%), 4/43 (9%), 3/43 (7%), and 3/43 (7%) of pregnancies, respectively. Second and third trimester ultrasound abnormalities included polyhydramnios, macrocephaly, macrosomia, and renal and cardiac abnormalities. Delivery occurred via spontaneous vaginal, operative vaginal, or cesarean delivery in 15/42 (36%), 7/42 (16%), and 20/42 (48%), respectively. Median gestational age at delivery was 37 weeks and median birth weight was 3501 grams. Germline pathogenic vaiants had mutiple congenital consequences including polyhydramnios, renal and cardiac abnormalities, macrosomia, and macrocephaly on second and third trimester ultrasound. Elevated rates of operative delivery and neonatal complications were also noted. Understanding and defining a prenatal phenotype may improve prenatal prognostic counseling and outcomes.

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“…Today, Sanger sequencing is the gold standard method for molecular diagnosis of RASopathies. Prenatal molecular diagnosis of CS is possible by ruling out the absence of HRAS mutations ( 4 ).…”

Section: Introductionmentioning

confidence: 99%

Recombinant GH treatment in a case of Costello syndrome with a 5-year follow-up

Cetin

Şıklar

Özsu

et al. 2020

Clin Pediatr Endocrinol

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. Costello syndrome (CS) is a rare member of the group of neuro-cardio-facio-cutaneous diseases known as RASopathies. CS involves characteristic dysmorphic craniofacial features, cardiac defects, and increased cancer susceptibility, depending on the heterozygous activating germline mutations in HRAS . Polyhydramnios and high birth weight are the most common presentations in the perinatal and neonatal periods; while poor postnatal growth, short stature, and failure to thrive are significant issues in infancy. Possible mechanisms of short stature in CS include GH deficiency and feeding difficulties. Only a few reported cases of CS with GH deficiency exist in literature. Here, we describe the 5-yr follow-up of a CS patient with complete GH deficiency treated with recombinant human GH (rhGH) from the age of four years. No significant adverse events regarding progression of hypertrophic cardiomyopathy and tumor development were observed. She has been responsive to treatment with improved growth velocity and height standard deviation scores. She is still under continuous monitoring for concerns on the possible development of cardiac events and malignancies. This case indicated that rhGH therapy is effective for improving the height and growth velocity of CS patients with GH deficiency under close cardiac and oncological monitoring.

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Next Generation Sequencing Approach in a Prenatal Case of Cardio-Facio-Cutaneus Syndrome

Cited by 7 publications

References 30 publications

Lymphatic Abnormalities in Noonan Syndrome Spectrum Disorders: A Systematic Review

Lymphatic Abnormalities in Noonan Syndrome Spectrum Disorders: A Systematic Review

Obstetrical and neonatal outcomes of cardio‐facio‐cutaneous syndrome: Prenatal consequences of Ras/MAPK dysregulation

Recombinant GH treatment in a case of Costello syndrome with a 5-year follow-up

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