From: The genetic basis of hydrocephalus: genes, pathways, mechanisms, and global impact
Citation | Title | Author affiliation | Case # | Ancestry | Study design | CNS phenotype | Non-CNS phenotype | Type of hydrocephalus | Genetic methodology | Genetic analysis | Inheritance | Genetic findings |
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Antwi et al., 2018 [340] | A novel association of campomelic dysplasia and hydrocephalus with an unbalanced chromosomal translocation upstream of SOX9 | Yale University, New Haven, CT, United States | 1 Subject | - | Case study | Hypoplastic C6 vertebral body, exaggerated cervical lordosis, and exaggerated thoracic kyphosis | Tracheobronchomalacia, cleft palate, retrognathia, hypertelorism, hypoplastic mandible | Communicating | WES, cytogenetics | Karyotyping, FISH, aCGH | De novo | 17q24.3 (SOX9) |
Avitan-Hersh et al., 2011 [341] | A case of H syndrome showing immunophenotye similarities to Rosai-Dorfman disease | Technion Institute of Technology, Haifa, Israel | 1 Subject, 2 Parents | Arab | Case study | Isolated hydrocephalus | Pulmonic stenosis, skin hyperpigmentation, hepatomegaly, splenomegaly, dilatation of the right renal pelvis | Communicating | TES | - | AR | 10q22.1 (SLC29A3 gene, encodes human equilibrative nucleoside transporter hENT3) |
Cauley et al., 2019 [342] | Overlap of polymicrogyria, hydrocephalus, and Joubert syndrome in a family with novel truncating mutations in ADGRG1/GPR56 and KIAA0556 | The George Washington University School of Medicine and Health Sciences, Washington, DC, USA | 2 Subjects, 2 Siblings, 2 Parents, Controls used | Sudanese | Case series | Psychomotor delay, intellectual disability, seizures, severe brain malformations, spasticity, hyperreflexia | Ptosis, unilateral ophthalmoplegia, and bilateral vertical ophthalmoplegia, muscle wasting | - | WES | Variant analysis, Sanger sequencing | AR | 16q21 (ADGRG1) And 16p12.1 (KIAA0556) |
Christofolini et al., 2006 [343] | Hydrocephaly, penoscrotal transposition, and digital anomalies associated with de novo pseudodicentric rearranged chromosome 13 characterized by classical cytogenetic methods and mBAND analysis | Departamento de Morfologia, Disciplina de Genética, Universidade Federal de São Paulo, São Paulo, Brazil | 1 Subject, 2 Parents | - | Case study | Corpus callosum agenesis | Imperforate anus with anocutaneous fistula, penoscrotal transposition, and digital reduction defects, short palpebral fissures, telecanthus, epicanthic folds, short nose with depressed nasal bridge and anteverted nostrils, posteriorly rotated ears, short neck | Obstructive | Cytogenetics | G-banding | De novo | 13q deletion |
Doherty et al., 2012 [344] | GPSM2 mutations cause the brain malformations and hearing loss in Chudley-McCullough syndrome | University of Washington, Seattle Children's Hospital, USA | 12 Subjects, Controls used | Mennonite, European American, Dutch | Case series | Bilateral sensorineural deafness, corpus callosum agenesis, arachnoid cysts, posterior agenesis of the corpus callosum, frontal polymicrogyria, frontal heterotopia, cerebellar dysplasia | Down slanting palpebral fissures and low-set, posteriorly rotated ears | Communicating, Obstructive | Genotyping, WES | SNP, sanger sequencing | AR | 1p13.3 (G protein-signaling modulator 2 gene, GPSM2) |
Forrester et al., 2002 [345] | Kousseff syndrome caused by deletion of chromosome 22q11-13 | Southern Illinois University School of Medicine, Springfield, Illinois, USA | 3 Subjects, 2 Controls | - | Case series | Intellectual disability | Lumbosacral myelomeningocele, cleft palate, and dysmorphic features consisting of low-set and posteriorly rotated ears, retrognathia, and clinodactyly of the fifth toes, cardiac anomalies | Obstructive | Genotyping, cytogenetics | FISH, karyotyping, microsatellite marker assay | AR | 22q11.2-microdeletion |
Furey et al., 2018 [8] | De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus | Yale University School of Medicine, New Haven, CT 06510, USA | 177 subjects, 1,789 controls | - | Case series | Isolated hydrocephalus | Â | Communicating, Obstructive | WES | Direct sequencing | De novo | 3p22.3 (TRIM71) 3p21.31 (SMARCC1 9q22.32 (PTCH1) |
Grosso et al., 2002 [346] | De novo complete trisomy 5p: clinical and neuroradiological findings | University of Siena, Siena, Italy | 1 Subject | - | Case study | Isolated hydrocephalus | Low-set, posteriorly rotated ears with reduced cartilage, up slanted palpebral fissures, epicanthus, hypertelorism, a wide and depressed nasal root, a short nose with anteverted nostrils, a long philtrum, retrognathia, an ogival palate, a short neck, abnormal palmar creases, and a bell-shaped trunk | - | Cytogenetics | FISH w/ WCP | De novo | trisomy 5p |
Jacquemin et al., 2020 [347] | TrkA mediates effect of novel KIDINS220 mutation in human brain ventriculomegaly | Université Libre de Bruxelles, 1070 Brussels, Belgium | 3 Subjects, 1 Control | Pakistan | Case series | Isolated hydrocephalus | Limb contractures, club feet | - | WES | Variant analysis | AR | 2p25.1 (homozygous variant of KIDINS220) |
Kline-Fath et al., 2018 [348] | Fowler syndrome and fetal MRI findings: a genetic disorder mimicking hydranencephaly/hydrocephalus | Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave., Cincinnati, OH, USA | 1 Subject | - | Case study | Thin cerebral cortex, cerebellum, brainstem, and spinal cord | Arthrogryposis, proliferative glomeruloid vasculopathy | Obstructive | WES | - | AR | 14q24.3 (FLVCR2 gene) |
Koenigstein et al., 2016 [349] | Chudley-McCullough Syndrome: Variable Clinical Picture in Twins with a Novel GPSM2 Mutation | Justus-Liebig-University, Giessen, Germany | 2 Subjects | Turkish | Case series | Callosal agenesis, interhemispheric cyst, frontal polymicrogyria | Sensorineural deafness | Communicating | - | - | AR | 1p13.3 (c.C1093T; p.R365X in GPSM2) |
Lahiry et al., 2009 [350] | A multiplex human syndrome implicates a key role for intestinal cell kinase in development of central nervous, skeletal, and endocrine systems | Robarts Research Institute, London, Ontario N6A 5K8, Canada | 6 Subjects, 3112 Controls | Amish | Case series | Cerebral anomalies | Facial dysmorphisms, eye anomalies, skeletal anomalies, pulmonary/GI/GU dysplasia | Communicating | Genotyping, TGS | SNP, autozygosity mapping, direct sequencing | AR | 6p12.1 (ICK p.R272Q mutation) |
Li et al., 2015 [351] | Congenital hydrocephalus and hemivertebrae associated with de novo partial monosomy 6q (6q25.3 → qter) | The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, People's Republic of China | 1 Subject | - | Case study | Isolated hydrocephalus | Lumbar hemivertebrae | - | Cytogenetics | CNV, aCGH, Karyotyping, FISH | - | deletion in chromosome region 6q25.3 → qter |
Maclean et al., 2004 (258) | Kousseff syndrome: a causally heterogeneous disorder | Sydney Children's Hospital, Sydney, Australia | 2 Subjects | Indonesian | Case series | Myelomeningocele, callosal hypoplasia, intellectual delay | Posteriorly rotated ears, a large nose, a smooth featureless philtrum, hypertrichosis and restricted ankle dorsiflexion, tetralogy of fallot | Obstructive | TES | Cycle sequencing | AR | 22q11.2-microdeletion |
Maclean et al., 2005 [352] | Axenfeld-Rieger malformation and distinctive facial features: Clues to a recognizable 6p25 microdeletion syndrome | The Children's Hospital at Westmead, Sydney, New South Wales, Australia | 1 Subject | Caucasian | Case study | Cerebellar hypoplasia, a deficient inferior vermis, hypoplasia of the pons, medulla, and posterior corpus callosum, and absent septum pellucidum | Axenfeld-rieger malformation, hearing loss, congenital heart disease, dental anomalies, developmental delay, and a characteristic facial appearance | Communicating | Cytogenetics, genotyping | Karyotyping, FISH, microsatellite marker assay, | De novo | 6p25 (deletion of the FOXC1/FOXF2/FOXQ1 forkhead gene cluster) |
Mero et al., 2017 [353] | Homozygous KIDINS220 loss-of-function variants in fetuses with cerebral ventriculomegaly and limb contractures | Oslo University Hospital, Oslo, Norway | 4 Subjects, 2 Parents | - | Case series | Callosum agenesis, small cerebellum | Limb contractures | Communicating | WES | Sanger sequencing, autozygosity mapping, | AR | 2p25.1 (homozygous frameshift variant in exon 24 in KIDINS220) |
Pappa et al., 2017 [354] | Exome analysis in an Estonian multiplex family with neural tube defects-a case report | University of Tartu, Riia 23b, 51,010, Tartu, Estonia | 3 Subjects, 2 Parents | Estonian | Case series | Spina bifida, aqueductal stenosis, intellectual delay | Gait and motor abnormalities | Obstructive | WES | Variant analysis | Maternal | 21q22.3 (CBS), 5p15.31 (MTRR), 1p36.22 (MTHFR), 19q13.33 (IL4I1), 8q24.3 (SCRIB1), 6p21.1 (PTK7), 7q21.13 (FZD1), 1q23.2 (VANGL2), 17p13.1 (DVL2), 18q21.1 (TCEB3B), 2q35 (PLCD4), 10q11.21 (RASSF4), and 6p25.1 (FARS2) |
Powis et al., 2018 [355] | Postmortem Diagnostic Exome Sequencing Identifies a De Novo TUBB3 Alteration in a Newborn with Prenatally Diagnosed Hydrocephalus and Suspected Walker-Warburg Syndrome | Ambry Genetics, Aliso Viejo, California, USA | 1 Subject, 2 Parents | Caucasian | Case study | Posterior fossa cyst, dandy walker malformation, seizures | Optic nerve abnormalities, abnormal renal function | - | Diagnostic exome sequencing | - | De novo | 16q24.3 (TUBB3) |
Rai et al., 2015 [356] | Cervicomedullary spinal stenosis and ventriculomegaly in a child with developmental delay due to chromosome 16p12.1 microdeletion syndrome | Midland Regional Hospital, Mullingar Westmeath, Ireland | 1 Subject | - | Case study | Macrocephaly | Significant delay in gross motor skills | - | Cytogenetics | aCGH | - | Chr. 16p12.2 deletion |
Su et al., 2021 [357] | Novel compound heterozygous frameshift variants in WDR81 associated with congenital hydrocephalus 3 with brain anomalies: First Chinese prenatal case confirms WDR81 involvement | Guangxi Health Commission Key Laboratory of Precise Diagnosis and Treatment of Genetic Diseases, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, China | 2 Subjects | Chinese | Case series | Cerebellar hypoplasia | Cleft lip and palate, hydrops fetalis, hepatomegaly | HYC3 | WES | Sanger sequencing, variant analysis | AR | 17p13.3 (WDR81) |
Yüksel et al., 2019 [358] | A homozygous frameshift variant in an alternatively spliced exon of DLG5 causes hydrocephalus and renal dysplasia | Centogene AG, Rostock, Germany | 1 Subject, 1 Control | - | Case study | Isolated hydrocephalus | Atrial and ventricular septal defects, cleft lip and palate, and a renal phenotype including multi-cystic dysplasia | Obstructive | WES | Variant analysis, sanger sequencing | De novo | 10q22.3 (DLG5) |