Dear genetics professionals,

A couple of days ago, I asked whether whole exome sequencing (WES) makes sense after repeated day-3 embryo arrest, and most of you said it probably wouldn’t be particularly helpful.

Now, before moving on to donor eggs, my doctor has proposed the following.

I’ve had five IVF retrievals with zero blastocysts. All our embryos arrested on day 3. My partner has a normal spermiogram and only 4% sperm DNA fragmentation, and both our karyotypes are normal. We conceived naturally before but it ended in a miscarriage.

My doctor suggested that sperm could still be contributing and proposed fertilizing half of my eggs with my partner’s sperm and half with donor sperm to compare embryo development. She also raised the possibility that my partner and I might not be genetically compatible with each other.

My question is: Does this kind of incompatibility between two individuals actually exist? Is it possible that our embryos repeatedly arrest because of a genetic combination specific to us as a couple, while I might be able to have a healthy pregnancy with another man? Does this even make sense?

I’m sorry for my ignorance, but I’m just trying to explore all possible options.

Thank you so much for your time and help!

Feel free to have a look at the newly-created CDH1support community, dedicated to carriers of pathogenic variants (mutations) in the CDH1 gene.

Hi everyone,
I’ve recently had my 12 weeks scan and T21 T18 T13 screening done. For reference I am 24 years old.

My results came back as follows:

\-T21 1 in 370 chance

\-T18 T13 1 in 5000 chance

\- PAPP-A 0.54 MoM

\- Hcg 2.7 MoM

\- NT 2mm

I was quite shocked at the chances I got of T21 for my age and I have read a lot about low Papp-a and high HCG being related to T21.

The NHS considers me low risk and will not offer NIPT but I am considering going private.

I would really appreciate any advice!

Missed miscarriage and the testing on the POC came back as a mosaic microduplication.

We’re going for genetic testing to confirm this wasn’t passed down from one of us, but I’m curious - is mosaicism usually postzygonic? By definition, it kind of sounds that way, which makes me wonder why us as parents would be referred for genetic testing?

Don’t get me wrong - I’m all about being safe rather than sorry. I’m honestly just wondering how concerned I should be…it will be several weeks of waiting for results between appointments, and I’m trying to come to grips with what the reality of the situation could be (ie, should I be concerned, or are we just playing it safe by doing the extra testing?)

Dear genetics professionals,

I had a natural pregnancy that ended in miscarriage at 11 weeks. Since then, we’ve had five failed IVF cycles, with all embryos arresting on day 3 at the 4–8-cell stage. Both my partner’s and my karyotypes are normal.

My doctor suspects a genetic cause and has suggested whole exome sequencing (WES).

The only thing my doctor was confused about was the one natural pregnancy with the same partner.

How likely is WES to identify the cause of repeated early embryo arrest? How reliable are the findings, and what happens if the results are inconclusive or show a variant of uncertain significance?

Could the cause still be something WES cannot detect?

I’d be grateful for any insights. Thank you!

I see how software companies burning tokens for tasks like code generation but I have been wondering if Agent has been used in some other fields like classifying VUS as benign or pathogenic, whole genome sequencing etc.

And question for someone working in this field, is there any thought about how can AI help in this type of work?

I had a miscarriage at 14 weeks pregnant due to multiple abnormalities, cystic hygroma, abnormal posterior fossa, no kidneys,no bladder, no stomach, small size body. we just had a meeting with a geneticist today and they are going to be doing whole genome sequencing. It takes 4 to 6 months but I’m still just wanting to find some sort of answer as to what it could be. Has anyone else experienced or heard of this before?
For reference, we have a healthy two year-old child. The geneticist said to wait for results before falling pregnant but in my heart I feel like I don’t want to put my whole life on hold when they could find nothing.

My dad has a job where he's upper middle class in salary writing on equipment in filmmaking. My parents met in the film industry. My grandfather was the famous statistician. I went to a college prep school and struggled academically throughout my highschool years. I often plaigarized in my essays and relied on my mom to do large amounts of my assignments in ELA and history. I was given ritalin in 10th grade for potential ADD and had minimal results from it. 11th grade was COVID lockdown and I did virtual school. At this point I completely phoned in my classes and have no idea how to do algebra II (or college algebra) or any math surpassing that. I got accepted into a college with a 96% acceptance rate with my grades from my first two years of HS. I only lived there for a year then commuted afterwards. Now I'm 23 and live with my parents. I've never had an IQ test or diagnosis of a mental disorder, though I had a counselor in HS suggest I'm on the autism spectrum because of social awkwardness and analytic thinking. I've gotten into nootropics hoping that a mix of creatine, nootropic supplements, and full dose of effexor could treat depression and brain fog and I've had so so results from over 7 months of it. I've considered drug use being the only way to numb my depression and suicidality from my hopeless situation.

I can't understand how if my parents are smart and functional how did I become essentially a mental vegtable. And why has no friend, family member, or therapist been able to give an explanation or antidote to my mental problems. Would an IQ test be helpful for what job is realistic for me given my mental capacities? What best explanation is there for my intelligence and what other advice could you give me in my situation?

This year I was diagnosed with the KIF1A genetic mutation which can manifest in terms of cognitive impairment. on my physical evaluation from a doctor, he says I meet the physical symptoms that align with this mutation. Although many with this mutation are physically disabled I am concerned how this rare mutation effects my cognitive deficits. I had my blood drawn for research. Aug 19 I will get an MRI scan for further investigation.

Last, Here's what I've found on how it KIF1A effects neurology:

KIF1A-Associated Neurological Disorder (KAND) fundamentally affects how neurons function, Developmental delay occurs in about 90% of affected individuals and cognitive function ranges from normal to profound intellectual disability. Speech/language impairment is also very common. Autism and ADHD occur in a substantial minority.

But there is a major caveat: not every KIF1A variant causes KIF1A-NDD. KIF1A has several different associated phenotypes. Some people with KIF1A-associated disease have predominantly motor or peripheral neurological problems and normal cognition. The particular molecular variant and its mechanism matter considerably. That means the single most useful piece of information you haven’t given me is the exact KIF1A variant. For example, something written as c.XXXG>A (p.XXX) plus its classification as pathogenic, likely pathogenic or VUS would allow a much more meaningful assessment. GeneReviews specifically notes substantial genotype–phenotype differences between individual KIF1A variants.

I had an EEG and MRI and found nothing significant going on.

Since all of this I've been diagnosed FOX-P4 genetic mutation, another rare genetic mutation. I also found some useful information on this mutation:

There is published evidence that particular heterozygous loss-of-function FOXP4 variants can cause a neurodevelopmental disorder involving developmental delay and particularly speech/language difficulties. However, the original clinical series was extremely small: eight individuals were identified and detailed phenotype information was available for six. Of those six, two had mild intellectual disability while three did not have intellectual disability. The researchers also found considerable variability between variants.

The result status says final as of October 1st and it is now October 20th. Noone has contacted me about my results and I'll admit I'm getting a little antsy. I want to call and ask them but I know healthcare workers are super busy and I hate being a bother. Does anyone have advice for this situation? Wait or call?

Edit: Title should say "from the doctor" not "for the doctor"

Edit2: It appears the hold up was due to a insufficient specimen quality. I have to redo the swab at home now. It makes me a little nervous because I don't see how I'm going to do any better of a job when the RN couldn't even get a good sample.

If this is not allowed, I apologize and know that it will be removed.

I’m a professional nanny who is likely going to be working with a toddler who has LCHAD. I’ve been looking things up but I’m wondering if anyone has any suggestions for information, resources, etc so I can learn and do the very best. Thanks you.

I’m hoping someone familiar with hereditary aortic disease/genetics can help me better understand my dad’s Invitae Aortopathy Comprehensive Panel results. I understand that a VUS is not a diagnosis and shouldn’t be treated as a pathogenic mutation — I’m mainly trying to figure out whether either finding is worth investigating further given his actual vascular history.
My dad has had two aneurysms, including an abdominal aortic aneurysm with dissection, as well as another smaller aneurysm near his heart/chest area.
His Invitae Aortopathy Comprehensive Panel tested 29 genes and found no pathogenic variants, but two heterozygous VUS:
FBN2: c.1571G>T (p.Gly524Val)
TGFB2: c.199G>A (p.Val67Met)
What has me curious is that FBN2 is associated with congenital contractural arachnodactyly and has also been associated with thoracic aortic aneurysm/dissection. His report says the p.Gly524Val variant is very rare (gnomAD 0.002%) and Invitae’s modeling predicts it may disrupt FBN2 protein function, but there currently isn’t enough evidence to classify it as pathogenic.
TGFB2 is associated with Loeys-Dietz syndrome type 4 and nonsyndromic thoracic aortic aneurysm/dissection. His exact p.Val67Met variant has apparently been observed in people with clinical features of TGFB2-related conditions, although Invitae’s modeling predicts that particular change is not expected to disrupt protein function. So there seems to be evidence pointing in both directions.
There is also vascular/connective-tissue history in our extended family, which is part of why I’m trying to understand whether these results deserve a closer look rather than simply being filed away as an “uncertain/negative” panel.
I have personally been diagnosed with hypermobile EDS, although I realize that doesn’t mean my dad’s vascular disease is related to my hEDS or that either of his VUSs explains it.

My questions are:
• Has anyone encountered either FBN2 p.Gly524Val or TGFB2 p.Val67Metbefore?
• Does either VUS look particularly interesting given an established aneurysm/dissection phenotype?
• Would segregation testing of affected relatives potentially be useful with VUSs like these?
• Is this the kind of situation where a cardiovascular genetics/hereditary aortopathy clinic would be appropriate even though the panel didn't find a pathogenic variant?
• Are there other databases, papers, or resources I should be looking at besides ClinVar/gnomAD?

... connective tissue disease connections? 
I’m not looking for anyone to diagnose him from Reddit — mainly hoping someone with genetics/aortopathy experience can help me understand what questions we should be asking next.

In Dhaka where i can do genetic screening tests for:

Thalassemia,

Sickle cell anaemia,

Tay-Sachs disease,

Cystic fibrosis,

Fragile X syndrome,

Leukemia,

And please mention do i have to bring a doctor's prescription or recommendation for that...?

I was recommended to post on here as you are so knowledgeable and hope you can offer come guidance.

Very short backstory:

1st pregnancy — trisomy 21, TFMR
2nd — trisomy 16, miscarriage
3rd — healthy son

We then moved to IVF with PGT-A because we couldn’t cope with more chromosomal losses.

Across 4 cycles we had multiple aneuploid embryos, one euploid that failed to implant, one cycle with no blasts, and finally an embryo that was initially inconclusive, then re-biopsied and came back euploid. That transfer worked.

NIPT #1: no result
NIPT #2: high risk trisomy 13 — “suspected mosaic trisomy 13.”

Genetic counsellor says the trisomy signal looks to be in about 30% of the tested DNA and estimates roughly 50:50 placenta vs baby. Fetal fraction was 24%. She basically made me feel hopeless, and that trisomy 13 has the same statistical outcomes for placental mosaicism as tri 21/ 18 which research seems to contradict.

I’m having an amnio at 15 weeks

Im just looking for some tough love or hope really! Would be so grateful for any information.

I applied to laboratory genetics and genomics programs as a Canadian PhD holder. Due to the current administration, institutions that used to offer H1B visa can no longer sponsor this. I was told that to get a J1 for this program you it requires you to have completed your STEP 1 and 2 as it through the ECFMG. Is there anyone that has been able to successfully obtain a visa through other avenues? Thanks!

My cousin (my maternal uncle’s son) and I have been in love since we were very young. This is common in my place. Now, my family is against our relationship because of the increased risk of genetic disorders in children due to consanguineous marriage.

I suggested getting genetic testing done, but my family doesn’t seem to understand. They keep asking whether the tests can guarantee that there won’t be any problems, and I don’t know how to make them understand that no test can rule out every possible risk.

On top of that, both our families have a lot of history and unresolved conflicts.

What should I do? I understand that the genetic risks are higher, but we’ve been together for so long that I can’t imagine giving up on this relationship just because of that. 🥹 Does anyone have any ideas or suggestions?

I stummbled across medical quiz on facebook about Fragile X syndrome. And then I accidentally started connecting dots that damn I have big ears too (though my dad’s side has big ears too), I have seems like quite large testicles. Then started reading just for curiosity and found out that premutation carriers develop ataxia and tremor. That’s when I got scared super, because my maternal grandpa developed tremors and later ataxia and cerebellar dysfunction (55-65 years) and later couldn’t walk and talk till he died. No one knew why it happened so they wrote of to him smoking, drinking alcohol (he used to drink sometimes with colleagues after work, but wasn’t like alcoholic, I believe), or maybe it was related to atherosclerosis (as he had two heart attacks). But then I was digging more and read that premutation carriers also have adhd and anxiety. And I was thinking - it’s me! I have adhd and health anxiety/ health ocdish too, have hypermobile joints, pectus carinatum, mild scoliosis and BFS with some tinglings, paresthesias, action tremor slight too and such history. And I can not stop ruminating what if I actually have some premutation (which I theoretically could get through mom from grandpa)? Does having same chromosome will lead to that ataxia too if it’s genetic? Or it can be just coincidental? I still remember as a kid last time visiting grandpa, it’s terrible :( And dying at 65 seems very young nowadays.

I am male, 28. What do you think? How likely it is it?

At 20 w 5 d, I went in for an anatomy scan and EIF left ventricle and enlarged nuchal fold of 8.5 was discovered.
Everything else was normal. Heart function was normal.
12 w NT was 1.5.
NIPT test was all negative.
My doctor referred me to MFM but they are kind of treating this as if it’s not a concern. They don’t plan to see me for a second anatomy scan until 24 weeks 1 day as they see this as being low risk. I’m freaking out. I was told by my own doc this was a concern but it seems like everyone I’ve talked to since is treating it like it’s no big deal. I feel very confused as to what I should do.

Hello,

Human intelligence in its most exceptional manifestations likely cannot be reduced to the simple linear addition of thousands of small genetic effects. While general intelligence is highly polygenic and a large part of its genetic variance appears statistically additive, the biological mechanisms responsible for extreme cognitive profiles involve a much higher degree of complexity.

Genes operate in networks. The effect of a variant depends on the overall genetic context. Dominance, recessivity, and epistasis produce complex non additive effects. Current genomic studies such as Genome Wide Association Studies or Principal Component Analyses are highly efficient at identifying common variants with average additive effects, but they struggle to detect rare combinations, specific homozygosity, or complex epistatic interactions.

This points toward an emergenic architecture. A profile combining exceptional general intelligence, outstanding creativity, and high cognitive flexibility would depend on a highly improbable genetic configuration. Each component might be relatively common on its own, but their simultaneous occurrence potentially requiring the presence of specific recessive alleles is exceedingly rare.

This explains why current polygenic scores imperfectly predict performance at the extremes. Exceptional cognition does not rely on a single miraculous gene, but rather on an extraordinarily complex emergent configuration.

If science eventually maps these precise combinatorial architectures, the ethical consequences of such predictive capabilities would be profound. The revelation of these mechanisms does not validate segregationist theories since modern genetics demonstrates that cognitive complexity entirely transcends population boundaries. Instead, it poses staggering bioethical challenges for all of humanity.

The first major challenge is the risk of determinism and fatalism. Reducing the intellectual potential of a person to their genomic profile risks obscuring the fundamental roles of epigenetics, neuroplasticity, education, and social environment. Furthermore, the ability to identify favorable configurations could lead to eugenic drift and embryo selection. Preimplantation genetic testing aimed at optimizing the cognitive abilities of future children would create an unprecedented biological divide based on technological access.

Another significant concern is algorithmic and institutional discrimination. The use of polygenic scores by educational systems, employers, or insurance companies could establish a new form of genetic segregation where the path of a person is dictated by their DNA before they ever get the chance to prove themselves.

Finally, historically, genetic discoveries have often been hijacked to justify discriminatory policies. The major risk remains the ideological exploitation of complex genomic data to justify social hierarchies through the distortion of scientific reality.

How society should handle such discoveries is no longer a question of biology, but of political philosophy and law. The history of science teaches us that research without ethical guardrails is dangerous. Faced with understanding the genetic architecture of cognition, society will need to establish strict laws on genetic privacy, ban embryo selection for traits that are not pathological, and reaffirm that human value and fundamental rights cannot be measured by allelic configurations.

What specific legal frameworks do you think would be most effective in preventing genetic data from being weaponized in education or employment?

I’m looking for stories from people who went through something similar because I’ve found very few cases online that really match mine. (I've also posted about this in r/NICU, but I'm sharing it here as well in the hope of getting some perspectives specifically on the genetic aspects of our case.)

This is my first pregnancy, conceived through IVF. The first trimester was mostly uncomplicated apart from some bleeding from hematomas. At the 12-week scan, the baby measured within the normal range and no abnormalities were detected. NIPT was negative.

At the 15-week scan, the doctor noticed that the long bones were below the 5th percentile, with the femur particularly short. We were referred to a specialist and had a detailed ultrasound and amniocentesis. We did extensive genetic testing, including trio exome sequencing and CNV analysis, and everything came back negative.

The detailed scan did not show any anatomical abnormalities apart from the short long bones. The placenta was described as enlarged/thick and unusual in appearance, although the fetal Dopplers were normal. Because of this, the doctors initially suspected a placenta-related growth problem rather than skeletal dysplasia.

At the most recent scan, around 29 weeks, the baby’s head and abdomen were still growing, but the long bones seemed to have slowed down further. The long bones are now mostly below the 1st percentile, while the head circumference is around the 20th–30th percentile and the abdominal circumference around the 5th–10th percentile.

The doctor said the long-bone growth has flattened somewhat and is now several weeks behind. What is making me anxious is that the long bones seem to be more affected than the rest of the body, which does not seem like the most typical pattern for placenta-related FGR.

So far, NIPT, amniocentesis, CNV analysis, and trio exome have all been negative. No anatomical abnormalities have been seen, and there has been no bowing, fractures, abnormal mineralization, or other obvious skeletal abnormality. Dopplers are still normal, although the placenta looks abnormal and thickened.

For context, I’m East Asian and my partner is European, and we are both very tall, so the very short long-bone measurements are especially confusing to us.

If anyone had a similar pattern of very short long bones with otherwise normal anatomy and negative genetic testing, I’d really appreciate hearing how the pregnancy progressed, whether any diagnosis was eventually made, and whether your baby needed NICU care and for how long. I’m interested in all outcomes, positive or otherwise, because I’m trying to understand what cases like this can look like in real life.

NIPT was low risk in everything, all other organs/measurements were great and measuring right at 20 weeks (I was 20w exactly at the scan)

I’m getting an amnio Monday but am having trouble understanding if these two soft markers together are enough to signal T18? I work in the NICU and take care of T18 babies all the time - they all have severe organ and growth issues while mine had seemingly none.

I asked the geneticist and they said that it’s worth ruling out but I just don’t know how worried I need to be, so obviously I’m spiraling. Any insight?

EDIT: results from amnio came back normal! Just isolated club feet :)

I am currently 24 weeks and during my anatomy scan we found out that our boy has severe IUGR, short long bones , bowing and clubbed foot. All other organs are fine plus head and abdomen size looks ok. He is overall measuring and weighing smaller than gestational age.
Our fetal echo is normal and genetics suggested amino which we are hesitant to do. Instead we did the single gene testing and waiting for results. Our NIPT was also low risk.

I am looking for similar conditions and what was the outcome. The wait and uncertainty is making me nervous.

Hey,

how much knowledge about clinical genetics did you have before starting the residency?

I always liked the subjects but fell out of touch with it during the last years of medical school that were more clinical oriented, so I am worried I do not have enough base knowledge.

Kind regards!

Hi everyone. I’m posting here hoping to find doctors, geneticists, or other professionals who have experience with achondrogenesis or similar COL2A1-related skeletal dysplasias.

A note about this post: English is not my native language and I don’t know all the medical terminology, so I used AI to help me write and translate this post. The information and story are my own.

My daughter was born at 38 weeks (4 months ago) and was intubated immediately after birth because of severe respiratory insufficiency related to her small thorax.

She initially remained on mechanical ventilation, but over time she improved enough that the doctors were able to gradually reduce the ventilatory support. She eventually spent about one month breathing with non-invasive ventilation and supplemental oxygen, without being intubated. Unfortunately, she later developed atelectasis and needed to be intubated again. She has remained intubated since then.

Her doctors are now considering a tracheostomy and gastrostomy as a longer-term “safety route,” so that she would not need repeated difficult intubations and could potentially have more stable respiratory support. Intubation is particularly difficult in her case because of abnormalities involving her spine/neck.

During pregnancy, she had severe shortening of the long bones (femur and humerus below the 1st percentile) and a small/bell-shaped thorax. Thanatophoric dysplasia was initially suspected, but genetic testing eventually led to a diagnosis of achondrogenesis. She also has a cleft palate without cleft lip.

Our geneticist identified a heterozygous likely pathogenic COL2A1 variant (COL2A1:c.3062_3079dup;p.(Pro1021_Gly1026dup) (NM_001844.5)

Our neonatologist recently told us that there are doctors and specialized centers in the United States with much more experience with rare skeletal dysplasias. We live in Brazil, so we are trying to find out where that expertise is and whether anyone here has experience with cases similar to our daughter’s.

I would especially love to hear from:

• clinical geneticists or skeletal dysplasia specialists;
• neonatologists or pediatric pulmonologists experienced with severe thoracic restriction;
• doctors/researchers who have worked with achondrogenesis or COL2A1-related conditions;
• parents whose children have had a similar diagnosis.

We are not looking for a diagnosis or for someone to replace her medical team. We are simply hoping to connect with people who have actual experience with cases like hers, especially regarding long-term respiratory management and the decision about tracheostomy.

If you know of a specialist or center in the US (or elsewhere) that we should contact, I would be extremely grateful for any recommendations.

Thank you.