Dr. Lumaka underscores the critical impact of underrepresentation in genetic studies on the ability to classify variants. “The lack of representation is a major issue. It prevents us from properly classifying certain variants, resulting in a lower diagnostic yield in our population compared to Europeans,” he explains. While many genetic variants in European populations are well-characterized, African populations face a significant data gap. This scarcity hampers the classification of novel variants and limits the ability to upgrade clinical diagnoses due to insufficient evidence.

Representation also plays a crucial role in clinical training. “If we had more faces from our community in medical literature, these patients could serve as a vital training resource for us and our students,” Dr. Lumaka notes. Representation in the literature, he emphasizes, enables clinicians to better recognize syndromes and improve diagnostic accuracy within their communities.

From a phenotyping perspective, he points out the importance of visual data. “The more African faces we have in the medical literature, the better we can identify critical phenotypes specific to our population. This representation not only aids in clinical diagnosis but also helps narrow down core phenotypes that are universally present in specific syndromes.”

Beyond equitable healthcare, increasing African genetic data enriches scientific understanding. “The more African data we have in the public domain, the better we can characterize gene functions and disease mechanisms,” Dr. Lumaka says. Integrating diverse data also helps identify shared disease phenotypes, bridging gaps between African and European presentations.

Dr. Lumaka’s research team focuses on developmental disorders, employing innovative approaches alongside traditional postnatal genetics. “We primarily see paediatric patients referred by neuro-paediatricians and decide who is likely to benefit from genetic sequencing,” he shares. However, they are now expanding into new areas, such as unique phenotyping projects and secondary findings research.

A notable breakthrough in their work involves secondary findings—unexpected genetic results unrelated to the primary diagnostic question. “We are collaborating with colleagues across Africa to deepen our understanding of secondary findings and develop context-specific guidelines,” Dr. Lumaka reveals. This initiative aims to bridge knowledge gaps and establish tailored standards for African populations.

While optimistic, Dr. Lumaka remains mindful of the challenges ahead. “Phenotyping has traditionally been the first step in selecting tests and reviewing variants,” he notes. However, as broad sequencing becomes more accessible, the reliance on phenotyping as a diagnostic tool is diminishing. “This shift introduces challenges, especially for genes without distinct phenotypic markers, making them harder for clinicians to interpret.”  He also highlights the complexities of diagnosing patients with multiple developmental disorders—a scenario more common in populations with higher rates of consanguinity. “Determining whether a patient has two distinct diseases is a critical question we must address,” he says.

Despite these hurdles, Dr. Lumaka sees a promising future driven by computational advancements and artificial intelligence. “AI and computational tools hold great potential, though the journey ahead is fraught with challenges,” he acknowledges. Overcoming these obstacles will require innovative strategies, cross-continental collaboration, and sustained investment in research and technology.

Dr. Aime Lumaka’s work exemplifies the transformative potential of genetic research tailored to underrepresented populations. By increasing African representation in genomic studies, fostering breakthroughs in phenotyping, and embracing cutting-edge technologies, he envisions a future where precision medicine becomes a reality for all. While the path ahead is filled with challenges, his dedication and vision offer hope for a more equitable and informed healthcare landscape in Africa.

Explore Dr. Aimee Lumaka’s latest research on the application of Face2Gene in African populations. This study evaluates the tool’s performance in recognition of the fragile X syndrome gestalt in Congolese subjects. Read the full study here: https://www.sciencedirect.com/science/article/abs/pii/S1769721223001258?via%3Dihub

The post Genetic Research in Africa: An Interview with Dr. Aime Lumaka appeared first on FDNA™.

Dr. Giulia Pascolini’s work underscores the critical intersection of genetics and dermatology. By deepening our understanding of the genetic underpinnings of dermatological anomalies, she paves the way for more accurate diagnoses and targeted treatments. Her insights highlight the need for collaboration between dermatologists and geneticists, ensuring that patients with complex genetic conditions receive the comprehensive care they need. As research in this field continues to evolve, Dr. Pascolini’s contributions will undoubtedly play a pivotal role in advancing our knowledge and improving patient outcomes. Check out her insights below:

Genetics and Dermatology: An Intricate Relationship

Dr. Pascolini highlights the significance of understanding the genetic basis of dermatological conditions, particularly those arising from chromatin disturbances. “These genetic disruptions can manifest as cutaneous anomalies, and while some associations are well-known, others remain underexplored. Rubinstein-Taybi syndrome is a prime example of the association being well-documented,” she notes. Similarly, Koolen de-Vries syndrome often presents with pigment anomalies, such as spots and multiple nevi. Other conditions involve anomalies of hair and its appendages: “Hypertrichosis, seen in Coffin-Siris syndrome and more generically in BAF-opathies, is another well-known but underemphasized association,” Dr. Pascolini explains. Furthermore, ADNP syndrome has recently been linked to distinct cutaneous characteristics. In a study published in the American Journal of Medical Genetics Part A, Dr. Pascolini and her colleagues described these skin features, uncovering not only graphical thickening but also specific morphological anomalies.

The Role of Dermatologists in Genetic Pathologies

When asked if dermatologists know when to refer patients to geneticists, Dr. Pascolini asserts that while dermatologists are familiar with well-known genetic-based skin conditions, they might be less aware of those linked to chromatin disorders. “It’s understandable,” she says, “since dermatologists don’t encounter these cases as frequently as clinical geneticists do.”She emphasizes the importance of educating dermatologists to recognize when a genetic evaluation is warranted, particularly for chromatin-related anomalies and other rare syndromic presentations, which can manifest with not only skin features but also with appendages anomalies (hair, teeth, nails), mostly in pediatric age.

Dr. Pascolini points out a specific sign that should raise suspicion among dermatologists: an accumulation around the elbow combined with facial dysmorphism, such as hypertelorism. “This characteristic should prompt further investigation into potential chromatin pathologies, including Wiedemann-Steiner syndrome” she advises.

Current Research and Future Directions

Dr. Pascolini’s current work at the Skin Rare Diseases Center of IDI-IRCCS, one of the most important Italian Clinical and Research Institutes for the skin diseases, investigating genetic aspects of skin pathologies and diseases with inherited oncological susceptibility, such as multiple and familial melanoma. Within these oncological susceptibility pathologies, syndromic forms, such as Rothmund-Thomson syndrome, also fall under her research scope. “These conditions are caused by genes that mediate DNA repair, making this an emerging and rapidly growing field,” she explains. In this group of genetic diseases are also encountered trichothiodystrophies, a very rare genodermatoses with peculiar hair pattern, which she is studying.

Her team is poised to join a national network for the Kleefstra syndrome, a project already underway in Lombardy. This initiative aims to establish a satellite Center across Italy for phenotypic characterization and material collection for in-depth genetic studies. Dr. Pascolini will play a crucial role in the clinical characterization of these patients in the regions of Central Italy, contributing her expertise to this collaborative effort.

Dr. Pascolini recounts a case where a child’s clinical presentation strongly resembled a published case, yet molecular analysis initially revealed no mutations. “Sometime later, the laboratory that conducted the analysis contacted me again, saying that the mutation was actually present in a different gene, but it resulted in a very similar phenotype”. Dr Giulia explains that for this particular case, Face2Gene was very useful because it confirmed the differential diagnosis and gave more basis to finding the mutation in a new gene, for a similar phenotype.

The post Interview with Dr. Giulia Pascolini: Unravelling the Genetic Underpinnings of Dermatological Anomalies appeared first on FDNA™.

I started using Face2Gene four years ago. What caught my attention then was not only the phenotypic facial analysis, but also the functionality of the Overview screen – where I fill out the patients’  info and the clinical notes. In many cases, I already had the patient chart including photos previously taken, so that I could easily use Face2Gene to capture the patient’s data, phenotype description and  measurements.

This saves me time during the consultation because Face2Gene does a calculation, provides all relevant links, and I don’t have to look in books for specific info and growth curves. Since I started using Face2Gene, it continues to improve and update, allowing me to use the image analysis technology more thoroughly. 

Today, Face2Gene is integrated into my daily practice and is an integral part of the anamnesis and workflow. I annotate the results of my patient’s physical examination directly in Face2Gene rather than in the medical record, and print the report from Face2Gene.

Check out how to incorporate Face2Gene into your workflow.

Face2Gene significantly helps us in our practice. Sometimes we have an idea of a possible syndrome, and Face2Gene confirms our hypothesis. And sometimes, the opposite happens. For example, I had a patient with Velo-Cardio-Facial Syndrome  (VCFS), but she didn’t have congenital heart disease, so I did not think this was the correct diagnosis. However, when I uploaded her photo to Face2Gene, the tool listed VCFS in a top rank. I still couldn’t believe it! But the genetic test came back indicating a microdeletion in chromosome 22, thus confirming the diagnosis.

I think artificial intelligence technology exists to help us as doctors. It will never replace the doctor in the clinic, but it will increasingly shorten the time to diagnosis and save us all much-needed time.

Want to master Face2Gene? Check out all the tutorials available

The post Using Face2Gene in the clinic even when the patient does not show clear dysmorphic features appeared first on FDNA™.

“Our clinic is made up of a combination of five geneticists and five genetic counselors. We’re very fortunate to be able to see people of all ages throughout their lifetimes and have no real limitations on the indications that we see. We see genetics cases across the board, whether it is kids with birth problems, developmental delays or older people with neurological findings,” said GC Samantha Augustyn. “Sometimes we have a straightforward diagnosis and can do very specific testing just to confirm what we think. Other times we must do whole exome sequencing or genome sequencing because we don’t quite know what the answer is.”

“Face2Gene complements our workflow and enables us to work as a team. Obviously, not everyone is seeing everything, and not everyone is an expert in every single area, but we all have a lot of experience between us. We use Face2Gene as a collaborative tool to talk about the patient and make sure there’s nothing that we are majorly missing.”

“We take a picture of as many of our patients as possible, specifically the undiagnosed ones, and follow it through. Genetic testing is done and when the report comes back, we go back to Face2Gene to see if the relevant syndrome appeared there.”

“Knowing that Face2Gene is a protected setting that our team can have access to, we use this tool to share information between us to not only see what the algorithm gives us back in terms of possible syndromes but also all the different professionals within the team can view the clinical notes. We can share this information and ask, ‘Has anyone ever seen somebody with these features before? Here are pertinent positives, here are pertinent negatives.‘ This helps build the story and solve the problem as a team.”

This allows a conversation that can add pertinent points to what the app is showing us, almost like a new person looking at it with an outsider’s perspective, that can bring something that is important to think about.

Find out more about how to use Face2Gene as a team

Contact support@fdna.com for a demo!

The post Samantha Augustyn talks about how she uses Face2Gene as a team appeared first on FDNA™.

She took time from her busy schedule to speak with us about the field of genetics in Georgia, how she uses Face2Gene in her practice and the importance of an early diagnosis.

FDNA: First, congratulations on being selected as a board member of the ESHG. How do you feel about that?

Dr. Tkemaladze: Being a board member of the ESHG is a great honor and responsibility, since I am the first physician from Georgia to achieve that. I applied for this position in order to promote my country in an international medical society and contribute to further development and awareness of human genetics in Georgia. This is very important, because, just as in many other countries, the awareness about the different rare diseases is still deficient. Many non-geneticists still do not ‘think genetic’ and find it difficult to recognize specific syndromes, so to raise awareness about this is very, very important and I hope integration in ESHG from this perspective will further help.

FDNA: In your practice, do you think awareness is one of the main challenges to diagnose a rare genetic syndrome?

Dr. Tkemaladze: I would say so. 15 years ago, genetics as a separate subject didn’t even exist at our university. At the time when I was a student, I was never taught medical genetics.

When the Department of Molecular and Medical Genetics was established at our university, I had just finished my PhD and was invited to be a teacher. This is when I had to dive and fall in love with genetics.  But so many doctors who finished university 10 or 15 years ago, they simply were not taught genetics. I think this is one of the major challenges we face and the reason why often the diagnosis may be missed.

Another challenge for diagnosing genetic conditions is the fact that genetic tests are still quite expensive, especially for a resource-limited country like Georgia. But through participation in international clinical trials and research or sponsored projects,  free testing  is offered to patients with certain diseases. We try to promote this information among doctors and tell them: “okay, we have a program for skeletal dysplasia or epilepsy that will be free of charge”. And then, they start referring more patients and diagnosis is established in many. I am happy to see the stable increase in awareness for last several years, which is due to improved education and research opportunities.

FDNA: You said that tests are expensive. How Face2Gene helps with this?

Dr. Tkemaladze: Face2Gene helps a lot. There is no ‘one, perfect’ test that can detect all types of genetic abnormalities and choosing the right test is very important. Especially when you are from a country where the resources are lacking and there are many destitute people. As clinicians, we should try to think and choose the most appropriate diagnostic test.

Often, in Georgia, because of significant price difference we may opt for panels instead of exomes, and it’s very important to choose the right panel. When I see patients with dysmorphic features, I upload the portrait into Face2Gene. If the app shows a high score for a certain syndrome or even if it shows top 5-10 syndromes with similar scores, this helps me to narrow down the list of possible syndromes and ensure the needed genes are included in the list of panels and increase the diagnostic yield.

Face2Gene also helps me to interpret results with VUS (variants of unknown significance) because sometimes exomes or panels report several variants in genes causing overlapping syndromes. How to differentiate between them? Face2Gene is very, very helpful in this aspect.

FDNA: Can you give me an example?

Dr. Tkemaladze: Yes, this is one of my favorite case, and actually it will be published soon. The story is about a child with developmental delay and very peculiar facial features, whose parents are first cousins and the grandparents from each side are also third cousins (double consanguinity). Due to this fact I had a strong suspicion of a recessive disorder. But then I uploaded the patient’s photos to Face2Gene and it showed a very high match to Coffin-Lowry Syndrome, which is a X-linked dominant disease.

I was somehow surprised, I thought maybe the program is not working well enough since I was expecting a recessive disorder. But then I discussed the case with the foreign colleague who completely agreed on the clinical diagnosis of Coffin-Lowry syndrome and offered to analyze RPS6KA3 gene (which is the only causative gene for this syndrome) within his research study and the mutation was indeed there. It was a de-novo mutation that has no relation to parental consanguinity.

That was a life lesson for me because often when we see consanguinity we narrow down our clinical judgement for recessive disorders and disregard the possibility of de novo mutations. But when you have this nice tool, Face2Gene, it enables you to think broader and not to be biased.

FDNA: Do you think Face2Gene could also help improve the awareness and referral of other medical specialties?

Dr. Tkemaladze: Definitely. Before the pandemic, we had several in-person workshops on how to navigate and operate with Face2Gene for medical professionals. The feedback was excellent, and doctors were very happy and comfortable to use this tool. Later on, I was receiving feedback from my colleagues like: “I saw a patient, and this is the syndrome that matched, what do you think?” Face2Gene creates this feeling for non-geneticists to be more comfortable with rare syndromes with morphology disorders.

No one knows every syndrome, especially non geneticists. When they have this simple and nice tool on hand, they get more confidence. It’s easy, it’s free, provides suggestions and effectively shortens time to diagnosis.

FDNA: What is the importance of an early diagnosis in rare genetic disease?

Dr. Tkemaladze: Diagnosis in general is important and early diagnosis specifically, because some conditions are treatable, and we should strive to have a diagnosis as early as possible.

Some people may even argue that many rare genetic diseases are not curable. Some say: “If you cannot correct the gene, what’s the use of doing this?” But then you see these families who have gone through so many doctors and they have spent so much money for unnecessary investigations which consume so much of their time, resources and energy.

At the end of the day parents are frustrated that their child has problems and no one can explain what’s behind it. When you don’t have a diagnosis, how do you know if it is treatable or not? I would say that it’s a misconception that genetic diseases are not treatable. Some are and I am sure, with the new developments and tools, many more will be in the near future – this is my vision.

Also, often parents of undiagnosed children tell me that they are afraid to have another child because they don’t want the disease to recur. When we have the diagnosis, we are able to give accurate risk estimations. The families with inherited conditions may opt for prenatal or preimplantation genetic testing, whereas those with de novo mutations will feel more confident to proceed further without any additional tests, since the recurrence risk in this case is less than 1%. In Georgia most of the population does not practice consanguinity and the majority of genetic diseases I observe are due to de novo mutations. Having healthy children is so important!

Moreover, information about the causation of the disease goes much beyond just the diagnosis for the parents or the patients. For example, a boy may have an X-linked recessive condition and he may have unaffected sisters who themselves may be at risk to be carriers with further recurrence risk in their future children. When we have the diagnosis, then this risk can be surely avoided.

I would say that medical genetics is a very special field of medicine, where our concern is not only an affected patient, but also other, sometimes distant, family members, bringing a sensitive issue of ethics as well.

FDNA: It really helps to improve lives then?

Dr. Tkemaladze: I always say that Face2Gene is not only for geneticists, but it’s useful for any healthcare provider or medical student. It is so important for doctors to detect and recognize dysmorphism, and then it takes only one minute to upload the photo, another minute to put the symptoms and in three minutes they may have a suggestion of a possible diagnosis.

I am happy and honored to be part of the scientific advisory board of FDNA.

FDNA: And we are honored to have you!

The post A conversation with a Geneticist: Dr. Tinatin Tkemaladze from Tbilisi, Georgia appeared first on FDNA™.