title: Congenital hydrocephalus in clinical practice: a genetic diagnostic approach.
abstract: Congenital hydrocephalus is a common and often disabling disorder. The etiology is very heterogeneous. Little is known about the genetic causes of congenital hydrocephalus. A retrospective survey was performed including patients with primary congenital hydrocephalus referred to the Department of Clinical Genetics between 1985 and 2010 by perinatologists, (child) neurologists or pediatricians. Patients with hydrocephalus secondary to other pathology were excluded from this survey. We classified patients with primary congenital hydrocephalus into two main groups: non-syndromic hydrocephalus (NSH) and syndromic hydrocephalus (SH). Seventy-five individuals met the inclusion criteria, comprising 36% (27/75) NSH and 64% (48/75) SH. In 11% (8/75) hydrocephalus was familial. The cause of hydrocephalus was unknown in 81% (61/75), including all patients with NSH. The male-female ratio in this subgroup was 2.6:1, indicating an X-linked factor other than the L1CAM gene. In the group of SH patients, 29% (14/48) had a known cause of hydrocephalus including chromosomal abnormalities, L1 syndrome, Marden-Walker syndrome, Walker-Warburg syndrome and hemifacial microsomia. We performed this survey in order to evaluate current knowledge on the genetic etiology of primary congenital hydrocephalus and to identify new candidate genes or regulatory pathways for congenital hydrocephalus. Recommendations were made concerning the evaluation and genetic workup of patients with primary congenital hydrocephalus. We conclude that further molecular and functional analysis is needed to identify new genetic forms of congenital hydrocephalus.
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center Rotterdam, The Netherlands.
authors.forename: J M A
authors.initials: JM
authors.lastname: Verhagen
authors.forename: C T R M
authors.initials: CT
authors.lastname: Schrander-Stumpel
authors.forename: I P C
authors.initials: IP
authors.lastname: Krapels
authors.forename: C E M
authors.initials: CE
authors.lastname: de Die-Smulders
authors.forename: F H M
authors.initials: FH
authors.lastname: van Lint
authors.forename: C
authors.initials: C
authors.lastname: Willekes
authors.forename: J W
authors.initials: JW
authors.lastname: Weber
authors.forename: A W D
authors.initials: AW
authors.lastname: Gavilanes
authors.forename: M V E
authors.initials: MV
authors.lastname: Macville
authors.forename: A P A
authors.initials: AP
authors.lastname: Stegmann
authors.forename: J J M
authors.initials: JJ
authors.lastname: Engelen
authors.forename: J
authors.initials: J
authors.lastname: Bakker
authors.forename: Y J
authors.initials: YJ
authors.lastname: Vos
authors.forename: S G M
authors.initials: SG
authors.lastname: Frints
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D054119:Arachnodactyly / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D016569:Blepharophimosis / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D002675:Child, Preschool; D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D003240:Connective Tissue Diseases / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D003286:Contracture / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D056915:DNA Copy Number Variations; D005260:Female; D018628:Gene Dosage; D006801:Humans; D006849:Hydrocephalus / Q000145:classification / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D007223:Infant; D007621:Karyotyping; D008297:Male; D009426:Netherlands; D039842:Neural Cell Adhesion Molecule L1 / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D012720:Severity of Illness Index; D058494:Walker-Warburg Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology
chemical_list: D039842:Neural Cell Adhesion Molecule L1