Diagnostic Criteria

Suggestive Findings

Classic early-onset and atypical later-onset SLC6A3-related dopamine transporter deficiency syndrome (DTDS) should be suspected in individuals with the following clinical and laboratory findings.

Clinical Findings

Classic early-onset DTDS

• Predominant features in infancy

• Onset usually within the first six months of life

• Early nonspecific clinical findings of irritability and difficulty feeding

• Axial hypotonia

• Delay in motor milestones

• Hyperkinetic movement disorder (chorea, ballismus, dystonia, orolingual dyskinesia) typically evident in infancy and early childhood; may persist into late childhood and adolescence

• Eye movement disorders including recurrent oculogyric crises, saccade initiation failure, ocular flutter, and eyelid myoclonus

Source: GeneReviews — "SLC6A3-Related Dopamine Transporter Deficiency Syndrome"

Differential Diagnosis

Hereditary and acquired disorders can present clinically with the manifestations of classic early-onset and atypical later-onset SLC6A3-related dopamine transporter deficiency syndrome (DTDS). Table 2. Genes of Interest in the Differential Diagnosis of SLC6A3-Related Dopamine Transporter Deficiency Syndrome

Management Guidelines

No clinical practice guidelines for SLC6A3-related dopamine transporter deficiency syndrome (DTDS) have been published. Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with a SLC6A3-related DTDS, the evaluations summarized (if not performed as part of the evaluation that led to the diagnosis) are recommended. Table 3. SLC6A3-Related Dopamine Transporter Deficiency Syndrome: Recommended Evaluations Following Initial Diagnosis

Source: GeneReviews — "SLC6A3-Related Dopamine Transporter Deficiency Syndrome"

Clinical Guidance

Although dopamine agonists are used as first-line treatment of dystonia in SLC6A3-related DTDS, bromocriptine and pergolide are generally avoided due to increased risk of pulmonary, retroperitoneal, and pericardial fibrosis. Drugs with anti-dopaminergic side effects (e.g., some antihistamines, sedatives, and dimenhydrinate) may exacerbate movement disorders. The antiemetics metoclopramide, prochlorperazine, and other medicines with anti-dopaminergic effects may exacerbate movement disorders and alternatives should be used (e.g., anti-serotonergic agents).

Source: GeneReviews — "SLC6A3-Related Dopamine Transporter Deficiency Syndrome"

Surveillance Guidelines

To monitor existing manifestations, the individual's response to supportive care, and the emergence of new manifestations, the evaluations summarized in are recommended. Table 5. SLC6A3-Related Dopamine Transporter Deficiency Syndrome: Recommended Surveillance

Source: GeneReviews — "SLC6A3-Related Dopamine Transporter Deficiency Syndrome"