Affiliation:
1. Service de médecine génomique des maladies rares, AP‐HP.Centre, Institut Imagine Hôpital Universitaire Necker‐Enfants Malades Paris France
2. Service d'Obstétrique—Maternité Chirurgie, Médecine et Imagerie foetales, AP‐HP.Centre Hôpital Necker Enfants Malades Paris France
3. Service d'Obstétrique Centre hospitalier du Mans Le Mans France
4. Service de Pédiatrie, génétique médicale Centre hospitalier d'Alençon Alençon France
5. AP‐HP.Centre Cardiologie Pédiatrique Hôpital Universitaire Necker‐Enfants Malades Paris France
6. Bioinformatics Platform, Institut Imagine INSERM UMR 1163 Paris France
Abstract
AbstractIntroductionCREBBP truncating mutations and deletions are responsible for the well‐known Rubinstein‐Taybi syndrome. Recently, a new, distinct CREBBP‐linked syndrome has been described: missense mutations located at the 3′ end of exon 30 and the 5′ portion of exon 31 induce Menke‐Hennekam 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 ReportTrio‐whole exome sequencing (WES) was performed in a fetus showing increased nuchal translucency persistence and aorta abnormalities at 28 weeks of gestation (WG).ResultsWES revealed a CREBBP de novo missense mutation (c.5602C>T; p.Arg1868Trp) in exon 31, previously reported as the cause of Menke‐Hennekam syndrome. Termination of pregnancy was performed at 32 WG. We further reviewed the prenatal signs of Menke‐Hennekam syndrome already reported. Among the 35 patients reported and diagnosed postnatally up to this day, 15 presented recognizable prenatal signs, the most frequent being intra‐uterine growth retardation, brain, and cardiovascular anomalies.ConclusionMenke‐Hennekam 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 Menke‐Hennekam 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.
Subject
Genetics (clinical),Genetics,Molecular Biology