Hydrocephalus with stenosis of aqueduct of Sylvius

General Information (adopted from Orphanet):

Synonyms, Signs: HYDROCEPHALUS, X-LINKED
AQUEDUCTAL STENOSIS, X-LINKED
XLAS HYDROCEPHALUS, X-LINKED, WITH CONGENITAL IDIOPATHIC INTESTINAL PSEUDOOBSTRUCTION, INCLUDED
HYCX
HSAS1
HSAS
X-linked acqueductal stenosis
X-linked hydrocephalus with stenosis of aqueduct of Sylvius
X-linked HSAS
Bickers-Adams syndrome
Number of Symptoms 24
OrphanetNr: 2182
OMIM Id: 307000
ICD-10: Q03.0
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 1.7 [Orphanet]
Inheritance: X-linked recessive
X-linked
[Orphanet]
Age of onset: Antenatal
Neonatal
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: L1 syndrome
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

L1 syndrome is a mild to severe congenital X-linked developmental disorder characterized by hydrocephalus of varying degrees of severity, intellectual deficit, spasticity of the legs, and adducted thumbs. The syndrome represents a spectrum of disorders including: X-linked hydrocephalus with stenosis of the aqueduct of Sylvius (HSAS), MASA syndrome, X-linked complicated hereditary spastic paraplegia type 1, and X-linked complicated corpus callosum agenesis (Orphanet, Dec 2016).

Symptom Information: Sort by abundance 

1
 (HPO:0000280) Coarse facial features Occasional [Orphanet] 189 / 7739
2
 (HPO:0000256) Macrocephaly 298 / 7739
3
 (HPO:0000486) Strabismus Occasional [Orphanet] 576 / 7739
4
 (HPO:0000639) Nystagmus Occasional [Orphanet] 555 / 7739
5
 (HPO:0001257) Spasticity 7645588 IBIS 251 / 7739
6
 (HPO:0001276) Hypertonia Very frequent [Orphanet] 317 / 7739
7
 (HPO:0002516) Increased intracranial pressure Very frequent [Orphanet] 47 / 7739
8
 (HPO:0001258) Spastic paraplegia 7645588 IBIS 97 / 7739
9
 (HPO:0004374) Hemiplegia/hemiparesis Very frequent [Orphanet] 158 / 7739
10
 (HPO:0001250) Seizures Occasional [Orphanet] 1245 / 7739
11
 (HPO:0001249) Intellectual disability 1089 / 7739
12
 (HPO:0001181) Adducted thumb 31 / 7739
13
 (HPO:0009600) Flexion contracture of thumb 2 / 7739
14
 (HPO:0001172) Abnormality of the thumb Frequent [Orphanet] 103 / 7739
15
 (HPO:0001387) Joint stiffness Occasional [Orphanet] 322 / 7739
16
 (HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
17
 (HPO:0002410) Aqueductal stenosis Very frequent [Orphanet] 19 / 7739
18
 (HPO:0007016) Corticospinal tract hypoplasia 1 / 7739
19
 (HPO:0007370) Aplasia/Hypoplasia of the corpus callosum Occasional [Orphanet] 180 / 7739
20
 (HPO:0012443) Abnormality of brain morphology Occasional [Orphanet] 45 / 7739
21
 (HPO:0001274) Agenesis of corpus callosum 142 / 7739
22
 (HPO:0001419) X-linked recessive inheritance 189 / 7739
23
 (HPO:0001331) Absent septum pellucidum 16 / 7739
24
 (HPO:0000238) Hydrocephalus Very frequent [Orphanet] 278 / 7739

Associated genes:

L1CAM;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) The X-linked recessive form of congenital hydrocephalus (HSAS) is the most common of the inherited forms of hydrocephalus. The phenotype consists of enlarged cerebral ventricles and mental retardation, and often includes spastic paraparesis and adducted thumbs. The most ...
Diagnosis OMIM Sajid and Copple (1968) found basilar impression (109500) as an associated feature in 2 brothers and suggested its usefulness in diagnosis.

Diagnosis of hydrocephalus is determined by brain imaging, and may be suspected if macrocephaly is ...
Clinical Description OMIM The hydrocephalus may become arrested and the principal manifestations may be mental deficiency and spastic paraplegia. Hypoplasia and contracture of the thumb are characteristic (Edwards, 1961) but were not present in any of the 7 affected males in ...
Molecular genetics OMIM The nature of the gene defect in X-linked hydrocephalus was established by the candidate gene approach. Schrander-Stumpel et al. (1990) noted that similar linkage of HSAS and the MASA syndrome (303350) to Xq28 and overlapping features of the ...
Population genetics OMIM In a Chicago study, Burton (1979) estimated that 'up to 25% of aqueductal obstruction in males may be the result of an X-linked recessive disorder.'

Rosenthal et al. (1992) noted that HSAS occurs in approximately 1/30,000 ...