Speeding Time to Diagnosis for Rare Disorders: A Comprehensive Guide

Rare chromosome disorders encompass a spectrum of conditions resulting from atypical chromosomal arrangements, deletions, duplications, or alterations. Unlike more common genetic anomalies, these disorders occur infrequently, making their identification and classification a very daunting task for healthcare professionals, simply because most clinicians don’t see them often and aren’t familiar with their presentations. 

This lack of familiarity can severely delay diagnosis – it takes an average of five to nine years for people living with rare disorders to get the correct diagnosis. However – as with all diseases and disorders – early diagnosis is critical to proper management and enhanced quality of life. 

In this blog, we’ll explore the complexities of diagnosing rare chromosome disorders, highlight how to better detect the early signs of chromosomal abnormalities in your clinic, plus offer tips for creating an effective care plan for patients.

The Challenge of Chromosomal Abnormalities

Chromosome abnormalities vary widely and are often elusive due to their differing names and infrequent occurrence. Common chromosomal disorders include trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). Yet, there exists a multitude of other conditions that are rarer and bear different names.

Detecting the Early Signs of a Chromosomal Abnormality

Chromosomal abnormalities encompass a wide spectrum of genetic variations that can manifest in various ways, making early detection essential to effective patient care. Due to their variety and uniqueness, abnormalities can be difficult to discern immediately, however some common signs should raise red flags. They include:

Delays in developmental milestones: Failure to thrive or delays in achieving developmental milestones such as sitting, crawling, walking, or speech milestones may signal underlying chromosomal anomalies.

Abnormal Physical Features and Growth Patterns: Distinctive facial characteristics, abnormal limb lengths, unusual head size, or disproportionate growth patterns may hint at underlying chromosomal anomalies.

Cognitive and Behavioural Differences: Cognitive and behavioural differences might manifest as intellectual disabilities, learning difficulties, behavioural challenges, or psychiatric conditions and could be indicative of chromosomal abnormalities.

Tests to Help Confirm Diagnosis 

If you suspect a chromosomal abnormality, there are a number of tests available to help confirm a diagnosis. Options include:

Karyotype Test

The karyotype test involves looking at individual blood or skin cells under a microscope and can help identify genetic problems as the cause of a disorder or disease. It’s crucial for determining mosaicism (when patient has two or more sets of cells that differ genetically from one another) and is effective for determining how many cells actually have a chromosome abnormality and how many cells have normal chromosomes. 

Microarray Test

Microarray tests are efficient tools for recognizing the number of gene copies with a thousand times more precision than karyotype tests, and are quickly becoming a first-tier genetic test. 

Efficacy of both Karyotype and Microarray tests depend on aspects such as the location and size of the genetic change and has no direct correlation with their impact on phenotype.

Fluorescence In Situ Hybridization (FISH)

FISH is a specialized molecular technique used to detect specific chromosomal abnormalities. It involves labeling specific DNA sequences with fluorescent probes that bind to complementary sequences on chromosomes. This targeted approach aids in identifying particular chromosomal anomalies, such as deletions or translocations, however you must know what you’re looking for for this test to be effective. (i.e., If you use FISH to probe for the centromere of chromosome 21 because you suspect a Down’s syndrome, but the child had trisomy 18, you wouldn’t see it because you’re just looking for the number of probes or fluorescent signals in any one cell for chromosome 21.)

Role of Genetic Counsellors

Understanding genetic tests and their results can be a complex task, often requiring specialist input. Genetic counsellors are well-versed in navigating the intricacies of genetic reports; their guidance based on specific lab results is invaluable in this context. Almost all labs have genetic counsellors on staff whose role is to help you interpret any abnormality you discover. They can also provide condition-specific information and guidance on referrals. With only about 10 percent of genes linked to the condition having an established cause or consequence, the knowledge provided by these professionals is invaluable.

Creating a Custom Care Plan

Once you have a diagnosis, you’re encouraged to dedicate time familiarizing yourself with the specific chromosomal anomaly in question. This is a patient you are likely going to see often, and the investment of time up-front will be crucial to helping preempt potential issues before they arise in the future. 

Parent support groups are a helpful resource for information, fostering connections, and providing support for families dealing with rare conditions. Empower parents to join you in actively looking for new information that you can review together to determine the best care plan. Ensuring everyone is actively committed to learning supports improved  patient outcomes.

Sharpen your skills around diagnosing rare disorders. Take our free course, Reducing the Time to Diagnosis: Chromosome Abnormalities, and get expert advice on recognizing early symptoms of chromosome abnormalities and steps to optimize patient management. 


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