What further testing should be done for a patient with an unknown condition?

From the Guidelines

For a patient with an unknown condition, the most appropriate further testing should include a comprehensive history and physical examination, followed by chromosomal microarray (CMA) and Fragile X testing as first-tier tests, as recommended by the American Academy of Pediatrics (AAP) and the American College of Medical Genetics and Genomics (ACMG) 1.

Initial Assessment

The initial assessment should involve a thorough clinical evaluation, including a detailed history and physical examination, to identify any potential signs or symptoms that could guide further testing. This approach is supported by various professional societies, including the AAP and the ACMG, which emphasize the importance of a comprehensive evaluation in patients with developmental delay (DD), intellectual disability (ID), or autism spectrum disorder (ASD) 1.

Genetic Testing

Genetic testing, such as CMA and Fragile X testing, should be considered as first-tier tests for patients with unknown conditions, particularly those with suspected DD, ID, or ASD. The ACMG recommends that exome sequencing (ES) or whole genome sequencing (WGS) should be a first- or second-tier test in all patients with unexplained DD/ID or congenital anomalies 1.

Stepwise Approach

A stepwise approach to testing is recommended, starting with less invasive, broader tests before proceeding to more specific and invasive investigations. This systematic approach helps avoid unnecessary testing while efficiently narrowing down potential diagnoses. Throughout this process, the patient's symptoms should be monitored and managed appropriately, and consultation with relevant specialists may be beneficial for complex presentations or when initial testing is inconclusive.

Specialist Referral

If the patient's condition remains unclear after initial testing, or if there are atypical findings, referral to a specialist, such as a clinical geneticist, may be necessary for further evaluation and guidance on additional testing, as recommended by the Alzheimer's Association 1.

Additional Testing

Additional testing, such as metabolic testing, may be considered based on the patient's clinical presentation and family history. The AAP recommends that metabolic testing be considered in patients with suspected GDD/ID if indicated by history and physical examination 1.

Patient Management

Throughout the diagnostic process, the patient's symptoms should be managed appropriately, and their quality of life should be prioritized. A comprehensive and systematic approach to testing, combined with specialist referral and patient-centered care, can help ensure the best possible outcomes for patients with unknown conditions.

From the Research

Further Testing for Unknown Conditions

To determine the appropriate further testing for a patient with an unknown condition, several factors must be considered, including the patient's symptoms, medical history, and physical examination results.

• The patient's symptoms and medical history can help guide the selection of diagnostic tests, as certain tests are more relevant to specific conditions 2.
• A physical examination can also provide valuable information and help identify potential causes of the patient's symptoms.
• Laboratory tests, such as complete blood counts and comprehensive metabolic panels, can be useful in evaluating patients with unknown conditions 3, 4.
• Imaging studies, such as chest x-rays and abdominal ultrasounds, may also be necessary to rule out certain conditions 5.
• The choice of diagnostic tests should be guided by the patient's specific symptoms and medical history, as well as the potential risks and benefits of each test 6, 2.

Diagnostic Test Selection

The selection of diagnostic tests should be based on the patient's individual needs and the potential usefulness of each test in establishing a diagnosis.

• Some tests, such as liver function tests, may be useful in evaluating patients with symptoms suggestive of liver disease 6.
• Other tests, such as electrocardiography and stress tests, may be more relevant to patients with symptoms suggestive of cardiovascular disease 2.
• The use of point-of-care tests, such as comprehensive metabolic panels, can help reduce the length of stay in the emergency department and improve patient outcomes 4.

Limitations of Diagnostic Testing

It is essential to recognize the limitations of diagnostic testing and the potential for false-negative or false-positive results.

• No single test can diagnose all conditions, and a combination of tests may be necessary to establish a diagnosis 2, 3.
• The interpretation of diagnostic test results should be guided by the patient's clinical presentation and medical history 6, 5.
• Further testing may be necessary to confirm or rule out a diagnosis, and patients should be monitored closely for any changes in their condition 3, 4.