Table 1 Aqueductal stenosis
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Alazami et al., 2019 [129] | A novel ISLR2-linked autosomal recessive syndrome of congenital hydrocephalus, arthrogryposis and abdominal distension | King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia | 2 Subjects, 8 Controls | Saudi | Case series | Generalized hypotonia, diminished reflexes | Arthrogryposis and abdominal distension | Obstructive | WES | Autozygome analysis; Variant analysis | AR | 13q21.32 (c.652 T > C, p.Y218H in PCDH9); 15q24.1 (c.1660delT, p.W554Gfs*40 in ISLR2) |
Allocco et al., 2019 [130] | Recessive Inheritance of Congenital Hydrocephalus with Other Structural Brain Abnormalities Caused by Compound Heterozygous Mutations in ATP1A3 | Yale University, New Haven, CT, United States | 1 Subject, 2 Parents | Caucasian | Case study | Open schizencephaly, type 1 Chiari malformation, and dysgenesis of the corpus callosum | – | Obstructive | WES | CNV, Sanger sequencing | AR | 19q13.2 (p.R19C in exon 2 and p.R463C in exon 11 of ATP1A3) |
Chassaing et al., 2007 [131] | Germinal mosaicism and familial recurrence of a SOX2 mutation with highly variable phenotypic expression extending from AEG syndrome to absence of ocular involvement | Hôpital Purpan, Toulouse, France | 1 Subject, 1 Control | – | Case study | Brain malformations, corpus callosum hypoplasia | Ocular dysgenesis, male genital tract malformations, postnatal growth retardation, and facial dysmorphic features | Obstructive | TGS | – | AD | 3q26.33 (deletion within SOX2) |
Cox et al., 1997 [132] | VACTERL with hydrocephalus in twins due to Fanconi anemia (FA): mutation in the FAC gene | Royal Postgraduate Medical School, Hammersmith Hospital, London, United Kingdom | 2 Subjects, 2 Parents | South African Ashkenazi Jew | Case study | Isolated hydrocephalus | Absent thumb, pericardial effusion, tracheo-esophageal fistula, pulmonary dysgenesis, intestinal malrotation, ectopic kidney, tetralogy of fallot | Obstructive | TGS | – | AR | 9q22.32 (IVS4 + 4 A to T splice mutation in intron 4 of FAC) |
De Keersmaecker et al., 2013 [133] | Prenatal diagnosis of MPPH syndrome | University Hospitals, Leuven, Belgium | 1 Subject | – | Case study | Polymicrogyria | Postaxial polydactyly | Obstructive | Cytogenetics, TGS | aCGH | – | – |
Escobar et al., 2009 [134] | Significant phenotypic variability of Muenke syndrome in identical twins | St. Vincent Children's Hospital, Indianapolis, Indiana, USA | 2 Subjects | – | Case study | Coronal craniosynostosis, porencephalic cyst, and absence of the corpus callosum | Bilateral sensorineural hearing loss, tracheoesophageal fistula, asd, vsd | Obstructive | TGS | – | De novo | 4p16.3 (c.C749G, p.P250R in FGFR3 gene) |
Gomy et al., 2008 [135] | Two new Brazilian patients with Gómez-López-Hernández syndrome: reviewing the expanded phenotype with molecular insights | School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil | 2 Subjects | Brazilian | Case study | Craniosynostosis, craniofacial anomalies, trigeminal anesthesia, cerebellar ataxia, intellectual disability, and rhombencephalosynapsis | Scalp alopecia, developmental delay | Obstructive | TGS | Direct sequencing | - | No pathogenic mutations |
Isik et al., 2018 (78) [136] | Clinical and genetic features of L1 syndrome patients: Definition of two novel mutations | Faculty of Medicine, Ege University, Izmir, Turkey | 2 Subjects | - | Case series | Intellectual disability, microcephaly, spasticity | Developmental delay, broad forehead, hypertelorism, low set ears, long philtrum, bilateral adducted thumbs, atrial septal defect | Obstructive | Molecular analysis, unspecified | De-novo mutation analysis, Segregation analysis | X-linked | Xq28 (c.3166 + 1G > A; c.749delG, p.S250Tfs*51) |
Jin et al., 2019 [137] | SLC12A ion transporter mutations in sporadic and familial human congenital hydrocephalus | Yale University School of Medicine, New Haven, CT, USA | 2 Subjects | - | Case series | Agenesis of the corpus callosum, and schizencephaly | - | Obstructive | WES | CNV | De novo | 15q14 (c.C1814T, p.Pr05L in SLC12A6); 5p15.33 (SLC12A7 deletion) |
Jouet et al., 1993 [138] | Refining the genetic location of the gene for X linked hydrocephalus within Xq28 | University of Cambridge | 4 Subjects | - | Case series | Seizures, intellectual disability, callosal agenesis, aqueduct stenosis, spastic paraparesis | Adducted thumbs | Obstructive | Genotyping | Two point/multipoint linkage analysis | X-linked recessive | Xq28 (HSAS gene proximal to DXS605 & coincident with DXS52) |
Khattab et al., 2011 [139] | A de novo 3.54 Mb deletion of 17q22-q23.1 associated with hydrocephalus: a case report and review of literature | Yale University School of Medicine, New Haven, Connecticut 06520–8064, USA | 1 Subject | - | Case study | Generalized hypotonia | Sutural separation with full anterior fontanel, small palpebral fissures, hypertelorism, low-set ears, micrognathia, downturned corners of the mouth, arachnodactyly of fingers and toes, contractures of joints | Obstructive | TGS, cytogenetics | aCGH; FISH | De novo | 17q22-q23.1 deletion |
Lamont et al., 2016 [140] | Expansion of phenotype and genotypic data in CRB2-related syndrome | Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada | 5 Subjects | - | Case series | Hypoplastic cerebellum, Subependymal heterotopias, hypertonia | Bilateral echogenic kidneys, hypoplastic right lung, hypoplastic right pulmonary artery, dextroposition of the heart, ASD defect, low visual acuity, irregular retinal pigmentation, mild optic atrophy | Obstructive | WES | NGS, Sanger sequencing, SNP genotyping array | AR, De novo, maternal | 9q33.3 (CRB2 mutations (p.C620S; p.R628C; p.C629S; p.G1036Afs*42; p.R1248Q; p.W498C; p.R633W; p.E643A; p.W759X; p.N800K; p.D1076A; p.C1098Sfs*53; p.R1115C; p.C1129R)); 4q27 (BBS7 mutation (p.R238Efs*59)); 1q25.2 (NPHS2 mutation (p.R229Q)) |
Lyonnet et al., 1992 [141] | The gene for X-linked hydrocephalus maps to Xq28, distal to DXS52 | Hôpital des Enfants-Malades, Paris, France | 58 Subjects | French, German | Case series | Intellectual disability and spasticity | Abnormal flexion deformity Of the thumbs | - | Haplotyping | Pairwise and multipoint linkage analysis | X-linked | HSAS1 localized to Xq28 and distal to DXS52 |
Maurya et al., 2021 [142] | A case report of Arnold Chiari type 1 malformation in acromesomelic dwarf infant | Seth Gordhandas Sunderdas Medical College and King Edward Memorial Hospital, Mumbai, Maharashtra, India | 1 Subject | - | Case study | Arnold Chiari type 1 malformation, atrophy of both lentiform nuclei, paucity of white matter in bilateral occipital regions, thinning of the corpus callosum | Acromesomelic dwarfism | Obstructive | WGS | NGS | AR | 4p16.3 (c.G1138A, p.G380R in exon 9 of FGFR3); 9p23 (c.G394A, p.G132S in exon 5 of MPDZ); 7q31.1 (c.T4133A, p.L1378H in exon 27 of LAMB1); 17q25.3 (c.A1G, p.M1V in exon 2 of GAA) |
Porayette et al., 2013 [143] | Novel mutations in geleophysic dysplasia type 1 | Boston Children's Hospital, Harvard Medical School, Boston, MA, USA | 1 Subject | - | Case study | Isolated hydrocephalus | Large head, prominent flat forehead, hypertelorism, wide mouth with long thin lips, full cheeks, downturned corners of the mouth, short palpebral fissures, long flat philtrum, grooved tongue with tongue-tie, low-set ears, small nose with depressed nasal bridge, short neck, mild abdominal distension, symmetrical shortening of all extremities, aortic stenosis, pulmonary valve stenosis | Obstructive | TGS | - | AD | 9q34.2 (c.1934G > A, p.R645H in exon 13 and mutation in intron 8) of ADAMTSL2) |
Serville et al., 1993 [144] | Prenatal exclusion of X-linked hydrocephalus-stenosis of the aqueduct of Sylvius sequence using closely linked DNA markers | Unité de Recherches sur les Handicaps Génétiques de l'Enfant INSERM U-12, Hôpital des Enfants-Malades, Paris, France | 2 Subject | - | Case series | Cortex thinning, spasticity, cerebral palsy, intellectual disability, corpus callosum agenesis, aqueductal stenosis | Bilateral adducted thumbs | Obstructive | Southern blotting, DNA probes; autoradiography | Linkage analysis | X-linked recessive | Xq28 region linkage with the HSAS locus |
Strain et al., 1994 [145] | Genetic heterogeneity in X-linked hydrocephalus: linkage to markers within Xq27.3 | Human Genetics Unit, University of Edinburgh, Western General Hospital, UK | 4 Subjects, Controls used | - | Case series | Septum pellucidum and corpus callosum agenesis, aqueductal stenosis | Adducted thumbs | Obstructive | Chromosomal banding | Two-point/multipoint linkage analysis | - | Linkage to DXS548 and FRAXA loci in Xq27.3 |
Tzschach et al., 2012 [146] | Interstitial 9q34.11-q34.13 deletion in a patient with severe intellectual disability, hydrocephalus, and cleft lip/palate | Institute of Human Genetics, University of Tuebingen, Tuebingen, Germany | 1 Subject, 2 Parents | - | Case study | Intellectual disability | Cleft lip and palate, bilateral talipes equinovarus, kyphoscoliosis, psychomotor development delay, short stature, bilateral convergent strabismus, dysmorphic facial features | Obstructive | Chromosome analysis | SNP array | - | 9q34.11–q34.13 (3.7 Mb deletion) |
Verbeek et al., 2012 [147] | COL4A2 mutation associated with familial porencephaly and small-vessel disease | Erasmus University Medical Center, Rotterdam, The Netherlands | 10 Subjects, Controls used | Caucasian, Afghani | Case series | Porencephaly, periventricular leukoencephalopathy, cerebellar hypoplasia, cerebral atrophy | Developmental delay, feeding difficulties, bilateral ica, ophthalmological signs | Obstructive | TGS | SNP array | AD | 13q34 (c.4165G4A, p.G1389R in exon 44 and c.3206delC in exon 34 in COL4A2) |
Vieira et al., 2012 [148] | Primary ciliary dyskinesia and hydrocephalus with aqueductal stenosis | Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, Lisbon, Portugal | 1 Subject | Gypsy | Case study | Aqueductal stenosis | Dextrocardia, a complex heart malformation, situs inversus, intestinal malrotation | Obstructive | TES | - | AR | No mutations in DNAI1 or DNAH5 |