Table 2 X-linked hydrocephalus
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
Alhousseini et al., 2019 [149] | Familial Hydrocephalus and Dysgenesis of the Corpus Callosum Associated with Xp22.33 Duplication and Stenosis of the Aqueduct of Sylvius with X-Linked Recessive Inheritance Pattern | Wayne State University, Detroit, Michigan, USA | 2 Subjects, 1 Control | Furey | Case study | Global motor delay | Â | Obstructive | Chromosomal microarray | CNV | X-linked Recessive | Xp22.33 (439Â Kb duplication) |
Beggs et al., 1992 [150] | Possible influences on the expression of X chromosome-linked dystrophin abnormalities by heterozygosity for autosomal recessive Fukuyama congenital muscular dystrophy | Howard Hughes Medical Institute, Children's Hospital, Boston, MA | 37 Subjects, Controls used | Japanese | Case series | Comedullar atrophy, cortical dysgenesis | Congenital muscular dystrophy | Communicating | TGS | Southern blotting | AR with X linked interaction | Xp21.2-p21.1 (exons 51–54 deletion in DMD) |
Berger et al., 2011 [38] | Early prenatal ventriculomegaly due to an AIFM1 mutation identified by linkage analysis and whole exome sequencing | Hadassah-Hebrew University Medical Center, Jerusalem, Israel | 2 Subjects, 86 Controls | Palestinian | Case Study | Bilateral septated choroid plexus cysts, enlarged cisterna magna, swallowing difficulties, hypotonia | Hypertrophic cardiomyopathy, dystrophic muscle changes | Obstructive | WES | Linkage analysis | X-linked | Xq26.1 (c.G923A, p.G308E in exon 9 of AIFM1) |
Cacciagli et al., 2013 [151] | AP1S2 is mutated in X-linked Dandy-Walker malformation with intellectual disability, basal ganglia disease and seizures (Pettigrew syndrome) | Faculté de Médecine de La Timone, Marseille, France | 4 Subjects, Control matched sampling | - | Case series | Dandy walker malformation, intellectual disability, self-harm, ataxia, limb scissoring, spasticity, kyphoscoliosis | Facial dysmorphism with a long and narrow face, prominent mandible, inconstant choreoathetosis | - | WES | SNP analysis; Sanger Sequencing | X-linked | Xp22.2 (c.G426 + 1 T mutation in exon 4 of AP1S2) |
Chassaing et al., 2005 [152] | X-linked dominant chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia | Hôpital Pellegrin, CHU Bordeaux, France | 4 Subjects | - | Case study | Macrocephaly | Microphthalmia, small low-set ears, and a short flat nose, platyspondyly, poor mineralization of the bones, 11 pairs of thin ribs, hypoplasia of the iliac wings, metaphyseal cupped phalanges, and hypoplastic bilobar-shaped calcaneus | - | TGS | Microsatellite marker assay; linkage analysis | X-linked dominant | X-linked dominant |
Furtado et al., 2010 [153] | A novel X-linked multiple congenital anomaly syndrome associated with an EBP mutation | University of Utah Health Sciences Center, Salt Lake City, Utah, USA | 1 Subject, 5 Controls | - | Case study | Dandy–walker malformation, dysgenesis of the corpus callosum, | Cataracts, bilateral cryptorchidism, collodian or ichthyotic skin, 2,3-toe syndactyly, robin anomaly, a high-nasal bridge, auricular dysplasia, and septal defects | Obstructive | TGS | Variant analysis, Sanger sequencing | X-linked recessive | Xp11.23 (c.G141T, p.W47C in exon 2 of EBP) |
Holden et al., 2006 [154] | Fanconi anaemia complementation group B presenting as X linked VACTERL with hydrocephalus syndrome | Guy's Hospital, St Thomas Street, London SE1 9RT, UK | 2 Subjects, 2 Controls | - | Case Study | Cervical vertebral defects, Arnold Chiari malformation, lumbar spina bifida occulta | Absent thumbs, unilateral renal agenesis, incomplete lung lobulation, cardiac defects, tracheoesophageal fistula/atresia, abnormal ear | Communicating | TGS | chromosome breakage assay, direct sequencing | X-linked | Xp22.2 (G to A substitution in intron 7 of FANCB which causes skipping of exon 7) |
Jouet et al., 1995 [155] | New domains of neural cell-adhesion molecule L1 implicated in X-linked hydrocephalus and MASA syndrome | University of Cambridge Department of Medicine, Addenbrooke's Hospital, United Kingdom | 9 Subjects | - | Case–Control | Intellectual disability, and spastic paraplegia type I | Aphasia, shuffling gait, adducted thumbs | - | TGS | Automated sequencing; SSCP; HA; direct radioactive cycle sequencing; SNuPE | X-linked | Xq28 (L1 gene mutations: c.G2302T, p.V768F; c.G361A, p.G121S; exon 1 (c.G26C, p.W9S); exon 8 (nucleotide G-to-A transition, p.E209K); exon 14 (c.C1756T, p.Q586X); exon 21 (c.C2822T, p.P941L); exon 24 (c.A3209G, p.Y1070C); base change at the intron 10 donor splice site resulting in the skipping of exon 10; point mutation in intron 26) |
Kaepernick et al., 1994 [156] | Clinical aspects of the MASA syndrome in a large family, including expressing females | Michigan State University | 22 Subjects | - | Case series | Intellectual disability, spasticity | Developmental delay, adducted thumbs, syndactyly of toes, rounded shoulders, shuffling gait, kyphosis, lordosis, hammer toes, metatarsus adductus, pes cavus, ankle | - | Southern blotting | DNA probing | X-linked | Mutation within Xq28 |
Kenwrick et al., 1986 [157] | Linkage studies of X-linked recessive spastic paraplegia using DNA probes | Nutfield Department of Clinical Medicine, John Radcliffe Hospital, OX39DU, Oxford, UK | 6 Subjects | - | Case series | Spastic paraplegia, intellectual disability | Absence of extensor pollicis longus | - | Southern blotting | Linkage analysis | X-linked | Mutation within Xq28 |
Ko et al., 1994 [158] | Prenatal diagnosis of X-linked hydrocephalus in a Chinese family with four successive affected pregnancies | National Taiwan University Hospital, Taipei, Republic of China | 4 Subjects | Chinese | Case study | Psychomotor delay, spastic quadriplegia, seizures | Aphasia | Obstructive | TES | Linkage analysis; direct sequencing | X-linked | Mutation within Xq28 |
Kolanczyk et al., 2015 [159] | Missense variant in CCDC22 causes X-linked recessive intellectual disability with features of Ritscher-Schinzel/3C syndrome | Institute for Medical Genetics and Human Genetics, Charité-Universitätsmedizin Berlin, Berlin, Germany | 2 Subjects, 1 Parent, 1 Control | Australian | Case study | Dandy–Walker malformation, cerebellar vermis hypoplasia, posterior fossa cysts, and ventricular dilatation, intellectual disability | Facial dysmorphism, cardiac defects, glaucoma, VSD, cryptorchidism | Obstructive | WES, cytogenetics | NGS-based WES, aCGH, segregation analysis, Sanger sequencing | X-linked recessive | Xp11.23 (c.A1670G, p.Y557C in exon 15 of CCDC22) |
Kroes et al., 2005 [160] | Cerebral, cerebellar, and colobomatous anomalies in three related males: Sex-linked inheritance in a newly recognized syndrome with features overlapping with Joubert syndrome | University Medical Center Utrecht, Utrecht, The Netherlands | 3 Subjects, 1 Control | Caucasian, Indonesian | Case study | Neural tube defect, convulsions, hypotonia, Dandy walker—cerebellar malformations, hypotonia, molar tooth sign, | Meckel’s diverticulum, Facial dysmorphism, bilateral colobomas | Communicating/Obstructive | TGS | X-inactivation status | X-linked recessive | X-linked inheritance |
Legius et al., 1994 [161] | Fine mapping of X-linked clasped thumb and mental retardation (MASA syndrome) in Xq28 | University of Michigan, Department of Pediatric Genetics, Ann Arbor | 49 Subjects | - | Case Study | Spastic paresis, Intellectual disability | Adducted thumbs, global physical delay | - | Haplotyping | Two-point and Multipoint linkage analysis | X-linked | Xq28 (Genetic etiology of MASA syndrome is localized to between DXS455 and F8C) |
McCauley et al., 2011 [162] | X-linked VACTERL with hydrocephalus syndrome: further delineation of the phenotype caused by FANCB mutations | GSTS Pathology, Guy's Hospital, London, UK | 10 Subjects, Controls used | - | Case series | Isolated hydrocephalus | Vertebral defects, hear anomalies, esophageal/duodenal/anal atresia, renal abnormalities, genital abnormalities (vacterl-h like phenotype) | - | TGS | Direct sequencing | X-linked, De novo | Xp22.2 (FANCB mutations: deletion of exons 8–10; c.2165 + 1G > T exon 9 donor splice site mutation; c.1857_1858delAG, p.R619fs; c.T2150G, p.L717X) |
Mikat et al., 2016 [163] | X-linked recessive VACTERL-H due to a mutation in FANCB in a preterm boy | University Hospital Essen, University Duisburg-Essen, Duisburg and Essen | 1 Subject, 1 Control | Caucasian | Case study | Isolated hydrocephalus | Bilateral renal agenesis, posteriorly rotated ears, retrognathia, oligodactyly of the hands, bilateral dysplasia of the radius and ulna, anal atresia, and myocardial hypertrophy | - | TGS | - | X-linked recessive | Xp22.2 (c.C832T, p.Q278X in FANCB) |
Peters et al., 2014 [42] | Focal dermal hypoplasia: report of a case with myelomeningocele, Arnold-Chiari malformation and hydrocephalus with a review of neurologic manifestations of Goltz syndrome | University of Calgary, Calgary, Alberta, Canada | 1 Subject | Nigerian | Case study | Arnold Chiari I malformation, lumbosacral meningomyelocele | Cryptorchidism, pointed chin and low set under folded ears with hypopigmentation of the helices linear hypoplasia and atrophy of the skin, bilateral iris and chorioretinal colobomas, syndactyly | Obstructive | TGS | a-CGH | X-linked, De novo | Xp11.23 (c853_855delACG in PORCN) |
Rietschel et al., 1991 [164] | MASA syndrome: clinical variability and linkage analysis | Institut für Humangenetik der Universität Bonn, Germany | 3 Subjects | - | Case series | Intellectual disability, spastic paraplegia | Aphasia, shuffling gait, and adducted thumbs | - | Chromosome analysis | Linkage analysis | X-linked | Mutation within Xq28 |
Rosenthal, Jouet, Kenwrick, 1992 [165] | Aberrant splicing of neural cell adhesion molecule L1 mRNA in a family with X-linked hydrocephalus | University of Cambridge, Addenbrooke's Hospital, UK | 2 Subjects, 2 Controls | - | Case–Control | Intellectual disability, spasticity | Adducted thumbs | - | TGS | Direct sequencing | X-linked | Xq28 (intronic A to C base change 19 bp upstream of a splice acceptor site in the L1 gene) |
Saillour et al., 2007 [39] | Mutations in the AP1S2 gene encoding the sigma 2 subunit of the adaptor protein 1 complex are associated with syndromic X-linked mental retardation with hydrocephalus and calcifications in basal ganglia | Institut Cochin, Université Paris Descartes, CNRS (UMR 8104), Paris, France | 8 Subjects | Scottish, French | Case series | Hypotonia, calcification of the basal ganglia, intellectual disability, seizures | Osteosclerosis of the calvarium, mild facial dysmorphism | Communicating/Obstructive | WGS | Microsatellite marker assay; linkage analysis, chromatographic mutation analysis | X-linked | Xp22.2 (c.288 + 5G > A in AP1S2) |
Schrander-Stumpel et al., 1990 [166] | MASA syndrome: new clinical features and linkage analysis using DNA probes | State University of Limburg, The Netherlands | 3 Subjects | - | Case series | Intellectual disability, macrocephaly, spastic paraplegia | Aphasia, shuffling gait, adducted thumbs, divergent strabismus, myopia, astigmatism, anteverted hip and shoulders, bowed knees, pupils irregularly shaped and not reactive to light, camptodactyly of fingers, dysarthria | - | Southern blotting | Linkage analysis | X-linked recessive | Mutation within Xq28 |
Serville et al., 1992 [167] | X-linked hydrocephalus: clinical heterogeneity at a single gene locus | CHU, Hôpital Pellegrin, Bordeaux, France | 3 Subjects | - | Case series | Cortex thinning, spasticity, cerebral palsy, intellectual disability, corpus callosum agenesis, aqueductal stenosis | Bilateral adducted thumbs | - | Southern blotting | Linkage analysis | X-linked | Mutation within Xq28 |
Sheen et al., 2004 [168] | Etiological heterogeneity of familial periventricular heterotopia and hydrocephalus | Beth Israel Deaconess Medical Center, Harvard Medical School, HIM 816, 4 Blackfan Circle, Boston, MA 02115, USA | 3 Subjects | Caucasian (Australian & American), Ethiopian | Case series | Periventricular heterotopia, callosal agenesis, hypotonia, Chiari I malformation and aqueductal stenosis, seizures | Pulmonary artery stenosis, cardiac defects, bilateral per planovalgus, bilateral knee recurvatum, bilateral hip dysplasia, dysmorphic facial features | Obstructive | TGS | Linkage analysis | X-linked, Autosomal | Xq28 |
Simon et al., 2010 [169] | A mutation in the 3'-UTR of the HDAC6 gene abolishing the post-transcriptional regulation mediated by hsa-miR-433 is linked to a new form of dominant X-linked chondrodysplasia | Laboratoire de Génétique Humaine, EA 4137, Université Victor Segalen Bordeaux 2, Bordeaux 33,076, France | 2 Subjects, 1 Control | - | Case series | Isolated hydrocephalus | Platyspondyly, rhizomelic shortening of the members, specific brachydactyly, hydrocephaly, facial dysmorphism and microphthalmia | - | TES, cytogenetics | Linkage analysis; aCGH | X-linked dominant | Xp11.23 (c.*281A > T in exon 29 of HDAC6 gene) |
Tripolszki et al., 2020 [170] | An X-linked syndrome with severe neurodevelopmental delay, hydrocephalus, and early lethality caused by a missense variation in the OTUD5 gene | CENTOGENE GmbH, Rostock, Germany | 13 Subjects, Controls used | Irish Caucasian | Case study | Severe neurodevelopmental delay, hypotonia | Growth retardation, congenital heart defects, hypospadias | Obstructive | WGS | Variant analysis | X-linked | Xp11.23 (c.G598A, p.E200K in exon 2 of OTUD5) |
Watanabe et al., 2018 [171] | X-linked VACTERL-H caused by deletion of exon 3 in FANCB: A case report | Yamagata University Faculty of Medicine, Yamagata, Japan | 1 Subject | - | Case study | Isolated hydrocephalus | Tetralogy of fallot, absence of pulmonary valve, tracheoesophageal fistula, esophageal atresia, bilateral radial aplasia, left renal dysplasia, duodenal atresia, imperforate anus, and cleft vertebrae | - | WES | CNV, MLPA analysis | X-linked | Xp22.2 (exon 3 deletion in FANCB) |
Willems et al., 1990 [172] | Assignment of X-linked hydrocephalus to Xq28 by linkage analysis | University of Antwerp-UIA, Wilrijk, Belgium | 7 Subjects, 34 Family Members, 55 Controls | Dutch, UK, USA | Case Series | Stenosis of the aqueduct of Sylvius, intellectual disability, spastic paraparesis | Clasped thumbs | - | X chromosome DNA marker probing | Southern Blot analysis, Linkage analysis | X-linked | mutation located on Xq28 |
Willems et al., 1992 [173] | Further localization of X-linked hydrocephalus in the chromosomal region Xq28 | University of Antwerp-UIA, Belgium | 20 Subjects, 84 Family Members | Netherlands, European, Israeli, German, French | Case series | Stenosis of the aqueduct of Sylvius, intellectual disability, and spastic paraparesis | Clasped thumbs | - | Southern blotting | Two-point and multipoint linkage analysis | X-linked | Gene mutations within Xq28 (between DXS52 and F8C) |
Zhang et al., 2021 [43] | A rare mutant of OFD1 gene responsible for Joubert syndrome with significant phenotype variation | West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, 610,041, China | 1 Subject, 5 Family Members, 201 Controls | - | Case study | Agenesis of cerebellar vermis and abnormal brain stem | Tetralogy of fallot | Obstructive | WES | Sanger sequencing | X-linked recessive | Xp22.2 (c.599 T > C, p.L200P in exon 8 of OFD1) |