Clinical Guidance

No clinically relevant genotype-phenotype correlations have been identified.

Source: GeneReviews — "PRICKLE1-Related Disorders"

Diagnostic Criteria

Suggestive Findings

PRICKLE1-related progressive myoclonus epilepsy (PME) with ataxia should be suspected in a child or adolescent with the following:

• Myoclonic seizures (lightning-like jerks)

• Generalized convulsive seizures

• Varying degrees of cognitive decline and motor impairment especially presenting with ataxia

• Family history consistent with autosomal recessive inheritance (e.g., affected sibs and/or parental consanguinity). Autosomal dominant transmission or absence of a known family history does not preclude the diagnosis.

Heterozygous PRICKLE1-related disorders should be considered in individuals with any combination of the following features:

• Seizures

• Developmental delay/ intellectual disability

• Autism spectrum disorder

• Central nervous system malformations

Establishing the Diagnosis

The ...

Source: GeneReviews — "PRICKLE1-Related Disorders"

Differential Diagnosis

Progressive myoclonic epilepsy (PME). This term covers a large and varied group of disorders characterized by myoclonus, generalized tonic-clonic seizures, and progressive neurologic deterioration. This group includes the following disorders that should be excluded before considering PRICKLE1-related PME with ataxia: EPM1 (Unverricht-Lundborg disease); PME, Lafora type; several forms of neuronal ceroid lipofuscinoses; myoclonus epilepsy with ragged-red fibers (MERRF); EPM3 (non-neuronal ceroid lipofuscinosis KCTD7-related PME); and types I and II sialidoses . Table 2. Disorders of Interest in the Differential Diagnosis of PRICKLE1-Related Progressive Myoclonus Epilepsy with Ataxia

Management Guidelines

Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a PRICKLE1-related disorder, 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 PRICKLE1-Related Disorders

Source: GeneReviews — "PRICKLE1-Related Disorders"

Clinical Guidance

Avoid the following drugs, which could worsen myoclonic seizures:

• Phenytoin

• Carbamezapine and oxycarbazepine

• Gabapentin, pregabalin, tiagabine, and vigabatrin

Source: GeneReviews — "PRICKLE1-Related Disorders"

Therapies Under Investigation

Search ClinicalTrials.gov in the US and EU Clinical Trials Register in Europe for access to information on clinical studies for a wide range of diseases and conditions. Note: No clinical trials are currently ongoing for PRICKLE1-related disorders.

Source: GeneReviews — "PRICKLE1-Related Disorders"

Surveillance Guidelines

Table 5.

Recommended Surveillance for Individuals with PRICKLE1-Related Disorders

System/Concern | Evaluation | Frequency

Neurologic

| Neurologic exam assessment for new onset or changes in seizures | Every 6 mos

Development

| • Developmental assessment incl speech, walking (mobility), coordination, handwriting

• Eval of school performance emotional status

| Every 6-12 mos (depending on age)

Source: GeneReviews — "PRICKLE1-Related Disorders"