IllnessHydrocephalus, X linked; differential diagnosis

NGS +

[Sanger]

A genetic etiology is suspected in nearly half of the cases of congenital hydrocephalus. However, only 3% of all cases are associated with defined gene mutations. The most common mutations involve the L1CAM gene, where the hydrocephalus is caused primarily by the obstructed flow of cerebrospinal fluid via an aqueductal stenosis. Here, the hydrocephalus is often severe, begins prenatally and may be the predominant clinical feature. On the other hand, L1CAM mutations cause the so-called L1 syndrome with two clinical phenotypes in addition to the mentioned X-linked hydrocephalus with stenosis of the Sylvian aqueduct: MASA syndrome (Mental Retardation, Aphasia, Spastic Paraplegia, Adducted Thumb) with X-linked complicated hereditary spastic paraplegia type 1 and finally X-linked complex agenesis of the corpus callosum. Yet aqueductal stenosis is not a constant feature of L1 syndrome. In addition, rarely, other mutated X-linked genes (AP1S2 etc.) as well as mutations in a number of autosomal genes may be responsible for hydrocephalus development. However, since most hydrocephalus cases are multifactorial, the molecular genetic yield is not yet well defined. An unremarkable genetic finding does not mean exclusion of the suspected clinical diagnosis.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1484/

• Alias: Hydrocephalus with stenosis of the aqueduct of Sylvius, HSAS
• Alias: XL acqueductal stenosis
• Alias: XL hydrocephalus
• Alias: XL hydrocephalus with stenosis of aqueduct of Sylvius
• Allelic: CRASH syndrome; Gareis-Mason syndrome (L1CAM)
• Allelic: Cardiac valvular dysplasia, XL (FLNA)
• Allelic: Cerebellar ataxia, mental retardation + dysequilibrium syndrome 2 (WDR81)
• Allelic: Chondrodysplasia punctata, XLD (EBP)
• Allelic: Congenital short bowel syndrome (FLNA)
• Allelic: Corpus callosum, partial agenesis of (L1CAM)
• Allelic: FG syndrome 2 (FLNA)
• Allelic: Frontometaphyseal dysplasia 1 (FLNA)
• Allelic: Heterotopia, periventricular, 1 (FLNA)
• Allelic: Hydranencephaly with abnormal genitalia (ARX)
• Allelic: Intestinal pseudoobstruction, neuronal (FLNA)
• Allelic: Lissencephaly, XL 2 (ARX)
• Allelic: MASA syndrome (L1CAM)
• Allelic: Otopalatodigital syndrome, type I (FLNA)
• Allelic: Otopalatodigital syndrome, type II (FLNA)
• Allelic: Partington syndrome (ARX)
• Allelic: Proud syndrome (ARX)
• Allelic: Spinocerebellar ataxia 40 (CCDC88C)
• Allelic: Terminal osseous dysplasia (FLNA)
• Allelic: VACTERL association, XL (ZIC3)
• Chondrodysplasia with platyspondyly, distinct brachydactyly, hydrocephaly, microphthalmia (HDAC6)
• Coffin-Lowry syndrome (RPS6KA3)
• Developmental + epileptic encephalopathy 1 (ARX)
• Fanconi anemia, complementation group B (FANCB)
• Hydrocephalus due to aqueductal stenosis (L1CAM)
• Hydrocephalus with Hirschsprung disease (L1CAM)
• Hydrocephalus with congenital idiopathic intestinal pseudoobstruction (L1CAM)
• Hydrocephalus, congenital, 1 (CCDC88C)
• Hydrocephalus, congenital, 2, with/-out brain or eye anomalies (MPDZ)
• Hydrocephalus, congenital, 3, with brain anomalies (WDR81)
• MEND syndrome (EBP)
• Melnick-Needles syndrome (FLNA)
• Mental retardation, XL 19 (RPS6KA3)
• Mental retardation, XL 29 + others (ARX)
• Mental retardation, XL 99 (USP9X)
• Mental retardation, XL 99, syndromic, female-restricted (USP9X)
• Mental retardation, XL syndromic 5 (AP1S2)
• Mental retardation, XL, syndromic 32 (CLIC2)
• Mucopolysaccharidosis II (IDS)
• Myotubular myopathy, XL (MTM1)
• VACTERL-H, XL (ZIC3)