Clinical Guidance

L1 syndrome is seen almost exclusively in males. Affected Males L1 syndrome comprises three clinical phenotypes ranging from severe to mild; its major features are hydrocephalus, intellectual disability, spasticity of the legs, and adducted thumbs. To date, more than 280 individuals have been identified with a pathogenic variant in L1CAM . compares the features among the various phenotypes associated with L1 syndrome. It is important to note that all phenotypes can be observed within the same family. Table 2. L1 Syndrome: Comparison of Phenotypes in Male Probands by Select Features Feature | L1 Phenotype

Diagnostic Criteria

Suggestive Findings

L1 syndrome involves a phenotypic spectrum ranging from severe to mild. L1 syndrome should be suspected in individuals with any of the following clinical phenotypes or neuroimaging findings and supportive family history.

Clinical Phenotypes

X-linked hydrocephalus with stenosis of aqueduct of Sylvius (HSAS). Signs present in affected males:

Source: GeneReviews — "L1 Syndrome"

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with L1 syndrome, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. Recommended Evaluations Following Initial Diagnosis in Individuals with L1 Syndrome

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with L1 Syndrome

System/Concern | Evaluation | Frequency

Hydrocephalus

| Neurologic eval | At regular intervals per individual patient

DD/ID

Spastic paraplegia