Cardio-facio-cutaneous syndrome and gastrointestinal defects: report on a newborn with 19p13.3 deletion including the MAP 2 K2 gene

Abstract

Background Cardio-facio-cutaneous syndrome (CFCS) belongs to RASopathies, a group of conditions caused by mutations in genes encoding proteins of the rat sarcoma/mitogen-activated protein kinase (RAS/MAPK) pathway. It is a rare syndrome, with about 300 patients reported. Main clinical manifestations include facial dysmorphisms, growth failure, heart defects, developmental delay, and ectodermal abnormalities. Mutations (mainly missense) of four genes (BRAF, MAP 2 K1, MAP 2 K2, and KRAS) have been associated to CFCS. However, whole gene deletions/duplications and chromosomal microdeletions have been also reported. Specifically, 19p13.3 deletion including MAP 2 K2 gene are responsible for cardio-facio-cutaneous microdeletion syndrome, whose affected subjects show more severe phenotype than CFCS general population. Case presentation Hereby, we report on a female newborn with prenatal diagnosis of omphalocele, leading to further genetic investigations through amniocentesis. Among these, array comparative genomic hybridization (a-CGH) identified a 19p13.3 microdeletion, spanning 1.27 Mb and including MAP 2 K2 gene. Clinical features at birth (coarse face with dysmorphic features, sparse and friable hair, cutaneous vascular malformations and hyperkeratotic lesions, interventricular septal defect, and omphalocele) were compatible with CFCS diagnosis, and further postnatal genetic investigations were not considered necessary. Soon after discharge, at around 1 month of life, she was readmitted to our Neonatal Intensive Care Unit due to repeated episodes of vomiting, subtending a hypertrophic pyloric stenosis (HPS) which was promptly identified and treated. Conclusions Our report supports the 19p13.3 microdeletion as a contiguous gene syndrome, in which the involvement of the genes contiguous to MAP 2 K2 may modify the patients’ phenotype. It highlights how CFCS affected subjects, including those with 19p13.3 deletions, may have associated gastrointestinal defects (e.g., omphalocele and HPS), providing further data on 19p13.3 microdeletion syndrome, and a better characterization of its genomic and phenotypic features. The complex clinical picture of such patients may be worsened by additional, and even precocious, life-threatening conditions like HPS. Clinicians must consider, anticipate and/or promptly treat possible medical and surgical complications, with the aim of reducing adverse outcomes. Extensive diagnostic work-up, and early, continuous, and multidisciplinary follow-up, as well as integrated care, are necessary for the longitudinal clinical evolution of any single patient.

Quality of life improving after propranolol treatment in patients with Infantile Hemangiomas

“…They significantly affect QoL of the families involved, and may also lead to potentially severe complications. Early management within reference centers allowing proper and prompt diagnosis, treatment and monitoring [ 15 – 18 ], should be guaranteed to affected subjects, in light of the known more favorable outcomes in addition to the positive effects on QoL.…”

Congenital hypopituitarism and multiple midline defects in a newborn with non-familial Cat Eye syndrome

“…A multidisciplinary (auxological/endocrinological, neurodevelopmental, surgical, ophthalmological, audiological, cardiological, orthopedic) management and longitudinal follow-up [21][22][23][24][25][26][27] must be guaranteed to affected subjects. The latter should be oriented to a prompt recognizing of complications and/or associated anomalies [28][29][30][31][32][33][34], allowing practitioners to thus lower mortality rates and short-and long-term adverse outcomes [35][36][37].…”

Comprehensive Analysis of Genomic Alterations in Hepatoid Adenocarcinoma of the Stomach and Identification of Clinically Actionable Alterations

“…Amplification of the CCNE1 locus in this region was synthetic lethal related, targeted by PKMYT1 kinase inhibition, and it was also a promising target in AFPGC, which warranted further research in HAS [ 10 , 33 ]. Deleted regions-associated studies were mainly involved in gastrointestinal defects, Peutz-Jeghers syndrome (19p13.3), and immunodeficiency (14q32.33) [ 34 , 35 , 36 , 37 ]. There were 32 regions specifically amplificated or deleted in HAS ( Figure S7C,D ), and the amplification of chr22q11.21 and deletions of chr1p36.21, chr7q11.21, chr7q22.1, chr9q12 as well as chr12q24.33 predicted a tendency of shorter OS.…”