Details of Disease

General Information of Disease (ID: DIS6QXIR)

• Disease Name: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
• Synonyms: HYCX; hydrocephalus due to congenital stenosis of aqueduct of Sylvius; HSAS1; XLAS; hydrocephalus, X-linked, with congenital idiopathic intestinal pseudoobstruction; hydrocephalus, X-linked; aqueductal stenosis, X-linked; HSAS; X-linked acqueductal stenosis; Bickers-Adams syndrome; hydrocephalus with hirschsprung disease, X-linked recessive; hydrocephalus with stenosis of the aqueduct of Sylvius; X-linked hydrocephalus with stenosis of aqueduct of Sylvius; hydrocephalus due to aqueductal stenosis, X-linked recessive; X-linked HSAS; X-linked hydrocephalus; X-linked hydrocephalus with stenosis of the aqueduct of Sylvius; hydrocephalus with congenital idiopathic intestinal pseudoobstruction, X-linked recessive
• Definition: A form of L1 syndrome caused by changes in the L1CAM gene characterized by severe hydrocephalus mostly with prenatal onset, signs of intracranial hypertension, adducted thumbs, spasticity, and severe intellectual deficit. HSAS represents the severe end of the spectrum and is associated with poor prognosis.
• Disease Hierarchy:
  DIS3PN9X: X-linked disease
  DISYPSZE: L1 syndrome
  DIS7O6UL: Congenital hydrocephalus
  DIS6QXIR: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius
• Disease Identifiers:
  MONDO ID: MONDO_0010611
  MESH ID: C536078
  UMLS CUI: C0265216
  OMIM ID: 236635
  MedGen ID: 75552
  Orphanet ID: 2182
  SNOMED CT ID: 71779008

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 2 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AVPR2	TTK8R02	Limited	Genetic Variation	[1]
L1CAM	TTC9D3K	Definitive	X-linked	[2]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
COL4A3	OT6SB8X5	Limited	Genetic Variation	[3]
COL4A4	OT9G0MCT	Limited	Genetic Variation	[3]
MYO1E	OTM9YSIZ	Limited	Genetic Variation	[4]
NRCAM	OT80HHQ2	Limited	Genetic Variation	[5]
ENOPH1	OTKXMWNN	moderate	Genetic Variation	[6]
CALM2	OTNYA92F	Strong	Genetic Variation	[7]
CAMKMT	OTLJBRUW	Strong	Genetic Variation	[7]
COL4A6	OTUREU5Z	Strong	Genetic Variation	[8]
KRIT1	OT58AP1I	Strong	Genetic Variation	[7]
COL4A5	OTHG60RE	Definitive	Genetic Variation	[9]
L1CAM	OTNWAQ4Y	Definitive	X-linked	[2]

References

• [1] Contiguous gene deletion involving L1CAM and AVPR2 causes X-linked hydrocephalus with nephrogenic diabetes insipidus.Am J Med Genet A. 2007 Mar 15;143A(6):594-8. doi: 10.1002/ajmg.a.31536.
• [2] Hereditary stenosis of the aqueduct of Sylvius as a cause of congenital hydrocephalus. Brain. 1949 Jun;72(Pt. 2):246-62. doi: 10.1093/brain/72.2.246.
• [3] Effect of heterozygous pathogenic COL4A3 or COL4A4 variants on patients with X-linked Alport syndrome.Mol Genet Genomic Med. 2019 May;7(5):e647. doi: 10.1002/mgg3.647. Epub 2019 Mar 18.
• [4] Coinheritance of COL4A5 and MYO1E mutations accentuate the severity of kidney disease.Pediatr Nephrol. 2015 Sep;30(9):1459-65. doi: 10.1007/s00467-015-3067-9. Epub 2015 Mar 5.
• [5] X-linked hydrocephalus: a novel missense mutation in the L1CAM gene.Pediatr Neurol. 2002 Oct;27(4):293-6. doi: 10.1016/s0887-8994(02)00440-x.
• [6] Multiple exon screening using restriction endonuclease fingerprinting (REF): detection of six novel mutations in the L1 cell adhesion molecule (L1CAM) gene.Hum Mutat. 1998;11(3):222-30. doi: 10.1002/(SICI)1098-1004(1998)11:3<222::AID-HUMU7>3.0.CO;2-J.
• [7] Nine novel L1 CAM mutations in families with X-linked hydrocephalus.Hum Mutat. 1997;9(6):512-8. doi: 10.1002/(SICI)1098-1004(1997)9:6<512::AID-HUMU3>3.0.CO;2-3.
• [8] Alport syndrome. An inherited disorder of renal, ocular, and cochlear basement membranes.Medicine (Baltimore). 1999 Sep;78(5):338-60. doi: 10.1097/00005792-199909000-00005.
• [9] Reassessing the pathogenicity of c.2858G>T(p.(G953V)) in COL4A5 Gene: report of 19 Chinese families.Eur J Hum Genet. 2020 Feb;28(2):244-252. doi: 10.1038/s41431-019-0523-1. Epub 2019 Oct 1.