Table 2.
X-linked hydrocephalus
| 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 | Obstructive | Chromosomal microarray | CNV | X-linked Recessive | Xp22.33 (439 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) |
Amplification created restriction site (ACRS). Array comparative genomic hybridization (aCGH). Atrial Septal Defect (ASD). Autosomal Recessive (AR). Central Nervous System (CNS), Copy number variant (CNV). Deep tendon reflexes (DTR). Denaturing gradient gel electrophoresis (DGGE). Fluorescein isothiocyanate (FITC). Fluorescence assisted mismatch analysis (FAMA). Mental retardation, aphasia, shuffling gait, and adducted thumbs syndrome (MASA syndrome). Multiplex ligation dependent probe amplification (MLPA). Restriction endonuclease fingerprinting (REF). Targeted exome sequencing (TES). Targeted genome sequencing (TGS). Ventricular septal defect (VSD). Whole exome sequencing (WES). Whole genome sequencing (WGS). Internal carotid artery (ICA)