From the Guidelines
The next best step in management and workup for a patient with an undiagnosed condition is to perform a comprehensive history and physical examination, followed by targeted genetic testing, such as chromosomal microarray (CMA) and Fragile X testing, as recommended by the American Academy of Pediatrics (AAP) and the American College of Medical Genetics and Genomics (ACMG) 1.
Initial Assessment
This initial assessment should include a detailed review of symptoms, past medical history, family history, social history, and medication use.
- A comprehensive history and physical examination are essential in identifying potential genetic disorders, such as autism spectrum disorder (ASD), global developmental delay (GDD), or intellectual disability (ID) 1.
- The AAP and ACMG recommend performing CMA and Fragile X testing as first-tier tests for patients with unexplained developmental delay or intellectual disability 1.
Targeted Laboratory Tests and Imaging Studies
Following the initial assessment, targeted laboratory tests and imaging studies should be ordered based on the clinical presentation and suspected diagnoses.
- The ACMG recommends considering exome sequencing (ES) or whole genome sequencing (WGS) as a first- or second-tier test for patients with unexplained developmental delay or intellectual disability 1.
- The AAP recommends considering metabolic testing if indicated by history and physical examination, and second-tier testing may include ES and gene panels 1.
Referral to Specialists and Symptomatic Management
If the diagnosis remains unclear after initial evaluation, consider referral to appropriate specialists based on the predominant symptoms or organ systems involved.
- Throughout this process, symptomatic management should be provided while the diagnostic workup continues, and regular follow-up appointments are essential to reassess the patient's condition and adjust the diagnostic strategy as new information becomes available 1.
- The use of contrast-enhanced CT scan is advocated for in certain populations, such as immunocompromised patients, to obtain a definitive diagnosis 1.
From the Research
Next Best Step in Management and Workup
The next best step in management and workup for a patient with an undiagnosed condition involves a thorough diagnostic approach.
- Identifying "red," "orange," and "green" flags in the patient's clinical presentation is crucial 2.
- A complete blood count (CBC) can be a useful initial test, as abnormalities in CBC parameters such as leucocytosis, neutrophilia, lymphopenia, and anemia can indicate the severity of certain conditions, like COVID-19 3.
- In patients with headache, a thorough understanding of secondary headache disorders and their clinical presentation is necessary, and particular attention should be paid to individual circumstances such as pregnancy, older age, and risk factors for alterations in intracranial pressure 2.
- Diagnostic tests should be evaluated for their clinical utility, which expresses the extent to which diagnostic testing improves health outcomes relative to the current best alternative 4.
- In geriatric patients, anemia is common and requires a thorough diagnostic workup to exclude other etiologies, and transfusions may be considered in symptomatic or severe cases 5.
Considerations for Specific Patient Populations
- In pregnant women, particular attention must be paid to the effects of blood pressure and hypercoagulability 2.
- In older adults, there is a need for higher suspicion for an intracranial mass lesion or giant cell arteritis 2.
- In patients with COVID-19 or long COVID-19, headache may have multiple etiologies and requires careful evaluation 2.