title: Choroidal abnormalities in café-au-lait syndromes: a new differential diagnostic tool?
abstract: The best known café-au-lait syndrome is neurofibromatosis type 1 (NF1). Legius syndrome (LS) is another, rarer syndrome with café-au-lait macules (CALMs). In young patients their clinical picture is often indistinguishable. We investigated the presence of choroidal abnormalities in syndromes with CALMs as a candidate tool for a more efficient diagnosis. Thirty-four patients with NF1 (14 with a truncating mutation, 14 with a non-truncating mutation and 6 with unknown mutation) and 11 patients with LS. All patients underwent an ophthalmological examination. Infrared images were performed. Choroidal nodules were diagnosed in 65% of the NF1 group. About 71% of NF1 patients with a truncating mutation and 50% of patients with a non-truncating mutation were found to have nodules. Choroidal nodules were seen in 18% of the LS patients, never more than one nodule/eye was detected in this group. Choroidal nodules are more abundantly present in NF1 genotypes with truncating mutations. In contrast, the number of choroidal nodules in LS is comparable with their presence in healthy individuals. Especially at an early age, when the clinical picture is incomplete, the detection of choroidal nodules is of diagnostic value, and helps in an appropriate genetic counselling and follow-up. These results support the suggestion to include choroidal nodules to the diagnostic criteria for NF1.
authors.affiliation: Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Cassiman
authors.affiliation: Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Casteels
authors.affiliation: Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Jacob
authors.affiliation: Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Plasschaert
authors.affiliation: Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Brems
authors.affiliation: Faculty of Medicine, Catholic University of Leuven, Leuven, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Dubron
authors.affiliation: Department of Ophthalmology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: K V
authors.initials: KV
authors.lastname: Keer
authors.affiliation: Department of Human Genetics, University Hospitals Leuven, Leuven, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Legius
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D019080:Cafe-au-Lait Spots / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D002829:Choroid / Q000503:physiopathology*; D003937:Diagnosis, Differential; D005817:Genetic Counseling; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D009456:Neurofibromatosis 1 / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D014792:Visual Acuity / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C504812:SPRED1 protein, human
keywords: Legius syndrome; Noonan syndrome with multiple lentigines; café-au-lait macules; choroidal abnormalities; neurofibromatosis