X-linked Hydrocephalus with Aqueductal Stenosis: L1CAM Gene Deletion/Duplication

Condition Description

Mutationof the L1CAM gene (Xq28) is characterized by hydrocephalus, mentalretardation, spasticity of the legs, and adducted thumbs. The phenotypicspectrum L1CAM mutations includes X-linked hydrocephalus with stenosisof the aqueduct of Sylvius (HSAS), MASA syndrome (mental retardation, aphasia(delayed speech), spastic paraplegia (shuffling gait), adducted thumbs), SPG1(X-linked complicated hereditary spastic paraplegia type 1), and X-linkedcomplicated corpus callosum agenesis. The group of conditions as a whole can bereferred to as L1 syndrome.

Hydrocephalusin L1 syndrome may be present prenatally and result in stillbirth or death inearly infancy. Males with HSAS are born with severe hydrocephalus and adductedthumbs. Seizures may occur. In less severely affected males, hydrocephalus maybe subclinically present and documented only because of developmental delay.Mild-to-moderate ventricular enlargement is compatible with long survival.Mental retardation is usually severe and is independent of shunting proceduresin individuals with severe hydrocephalus. In MASA syndrome, mental retardationranges from mild (IQ of 50-70) to moderate (IQ of 30-50). The degree ofintellectual impairment does not necessarily correlate with head size orseverity of hydrocephalus; males with severe mental retardation and a normalhead circumference have been reported. All phenotypes can be observed inaffected individuals in the same family. Females may manifest minor featuressuch as adducted thumbs and/or subnormal intelligence. Rarely do femalesmanifest the complete L1 syndrome phenotype.

X-linkedhydrocephalus with stenosis of the aqueduct of Sylvius is the most commongenetic form of congenital hydrocephalus, with a prevalence of approximatelyone in 30,000. This accounts for approximately 5%-10% of males withnonsyndromic congenital hydrocephalus.

Whilemutation detection rates are unknown, point mutations, partial gene deletions,and partial gene duplications have all been reported. Although uncommon, denovo disease-causing mutations have been reported.

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Genes (1)

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This test is indicated for:

  • Confirmation of a clinical diagnosis of L1 syndrome in individuals who have tested negative for sequence analysis
  • Carrier testing in adult females with a family history of L1 syndrome who have tested negative for sequence analysis


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Sequencing analysis of the L1CAM gene is available and is required before deletion/duplication analysis.
  • ACGH array-based test for deletion/duplication analysis of 109 differentX-linked intellectual disability genes is available.
  • Prenataltesting is available to adult females who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.

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