title: Phenotype analysis impacts testing strategy in patients with Currarino syndrome.
abstract: Currarino syndrome (OMIM 175450) presents with sacral, anorectal, and intraspinal anomalies and presacral meningocele or teratoma. Autosomal dominant loss-of-function mutations in the MNX1 gene cause nearly all familial and 30% of sporadic cases. Less frequently, a complex phenotype of Currarino syndrome can be caused by microdeletions of 7q containing MNX1. Here, we report one familial and three sporadic cases of Currarino syndrome. To determine the most efficient genetic testing approach for these patients, we have compared results from MNX1 sequencing, chromosomal microarray, and performed a literature search with analysis of genotype-phenotype correlation. Based on the relationship between the type of mutation (intragenic MNX1 mutations vs 7q microdeletion) and the presence of intellectual disability, growth retardation, facial dysmorphism, and associated malformations, we propose a testing algorithm. Patients with the classic Currarino triad of malformations but normal growth, intellect, and facial appearance should have MNX1 sequencing first, and only in the event of a normal result should the clinician proceed with chromosomal microarray testing. In contrast, if growth delay and/or facial dysmorphy and/or intellectual disability are present, chromosomal microarray should be the first method of choice for genetic testing.
authors.affiliation: Faculty of Medicine, University of Belgrade, Belgrade, Serbia.|Department of Medical Genetics, University Children's Hospital, Belgrade, Serbia.
authors.forename: G
authors.initials: G
authors.lastname: Cuturilo
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.|Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Hodge
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: C K
authors.initials: CK
authors.lastname: Runke
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: Thorland
authors.affiliation: Department of Medical Genetics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.|Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
authors.forename: M A
authors.initials: MA
authors.lastname: Al-Owain
authors.affiliation: Department of Genetics, Kaiser Permanente Medical Center, San Francisco, CA, USA.
authors.forename: J W
authors.initials: JW
authors.lastname: Ellison
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA.|Department of Medical Genetics, Mayo Clinic, Rochester, MN, USA.
authors.forename: D
authors.initials: D
authors.lastname: Babovic-Vuksanovic
mesh_terms: D000465:Algorithms; D001003:Anal Canal / Q000002:abnormalities*; D002675:Child, Preschool; D002869:Chromosome Aberrations; D004065:Digestive System Abnormalities / Q000175:diagnosis* / Q000235:genetics*; D019066:Facies; D056726:Genetic Association Studies; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D007621:Karyotyping; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D010641:Phenotype; D012007:Rectum / Q000002:abnormalities*; D012447:Sacrum / Q000002:abnormalities*; D013131:Spine / Q000473:pathology; D013595:Syringomyelia / Q000175:diagnosis* / Q000235:genetics*
keywords: Currarino syndrome; MNX1 gene; chromosomal microarray; distal 7q deletions; sequencing; testing algorithm