Novel de novo mutation affecting two adjacent aminoacids in the EED gene in a patient with Weaver syndrome.

Overgrowth, macrocephaly, accelerated osseous maturation, variable intellectual disability, and characteristic facial features are the main symptoms of Weaver syndrome, a rare condition caused by mutations in EZH2 gene. Recently, in four patients with Weaver-like symptoms without mutations in EZH2 gene, pathogenic variants in EED were described. We present another patient clinically diagnosed with Weaver syndrome in whom WES revealed an EED de novo mutation affecting two neighboring aminoacids, NM_003797.3:c.917_919delinsCGG/p.(Arg306_Asn307delinsThrAsp) located in one allele (in cis). Our observation, together with previous reports suggests that EED gene testing is warranted in patients with the overgrowth syndrome features and suspicion of Weaver syndrome with normal results of EZH2 gene sequencing.

MAP2K2 mutation as a cause of cardio-facio-cutaneous syndrome in an infant with a severe and fatal course of the disease.

Cardio-facio-cutaneous syndrome (CFCS), a rare congenital disorder of RASopathies, displays high phenotypic variability. Complications during pregnancy and in the perinatal period are commonly reported. Polyhydramnios is observed in over half of pregnancies and might occur with fetal macrocephaly, macrosomia, and/or heart defects. Premature birth is not uncommon and any complications like respiratory insufficiency, edema, and feeding difficulties are present and might delay accurate clinical diagnosis. Besides neonatal complications, CFCS newborns and later infants have distinctive dysmorphic features usually accompanied by neurological (hypotonia with motor delay, neurocognitive delay) findings. Also, heart defects usually present at birth. Herein, we present the case of a female baby born prematurely from a pregnancy complicated with polyhydramnios, presenting at birth with craniofacial features typical for RASopathies, heart defects, neurological abnormalities, and hyperkeratosis unusual for a neonatal period. Due to the presence of a heart defect and other complications related to premature birth, the course of the disease was severe with a fatal outcome at the age of 9 months. The RASopathy, particularly CFCS, clinical diagnosis was confirmed and de novo p.Phe57Ile mutation in MAP2K2 was identified.