2 research outputs found
Novel CDK10 variants with multicystic dysplastic kidney, left ventricular nonâcompaction, and a solitary median maxillary central incisor
International audienc
Diagnosis of MenkeâHennekam syndrome by prenatal whole exome sequencing and review of prenatal signs
Abstract Introduction CREBBP truncating mutations and deletions are responsible for the wellâknown RubinsteinâTaybi syndrome. Recently, a new, distinct CREBBPâlinked syndrome has been described: missense mutations located at the 3âČ end of exon 30 and the 5âČ portion of exon 31 induce MenkeâHennekam syndrome. Patients with this syndrome present a recognizable facial dysmorphism, intellectual disability of variable severity, microcephaly, short stature, autism, epilepsy, visual and hearing impairments, feeding problems, upper airway infections, scoliosis, and/or kyphosis. To date, all diagnoses were made postnatally. Method and Case Report Trioâwhole exome sequencing (WES) was performed in a fetus showing increased nuchal translucency persistence and aorta abnormalities at 28âweeks of gestation (WG). Results WES revealed a CREBBP de novo missense mutation (c.5602C>T; p.Arg1868Trp) in exon 31, previously reported as the cause of MenkeâHennekam syndrome. Termination of pregnancy was performed at 32 WG. We further reviewed the prenatal signs of MenkeâHennekam syndrome already reported. Among the 35 patients reported and diagnosed postnatally up to this day, 15 presented recognizable prenatal signs, the most frequent being intraâuterine growth retardation, brain, and cardiovascular anomalies. Conclusion MenkeâHennekam is a rare syndrome with unspecific, heterogeneous, and inconstant prenatal symptoms occurring most frequently with the c.5602C>T, p.(Arg1868Trp) mutation. Therefore, the prenatal diagnosis of MenkeâHennekam syndrome is only possible by molecular investigation. Moreover, this case report and review reinforce the importance of performing prenatal WES when unspecific signs are present on imaging