Researchers from Redcliffe Labs have highlighted the importance of considering family history, genetic counselling and advanced genomic testing alongside traditional prenatal investigations, especially in cases involving a history of unexplained childhood illness, developmental problems or recurrent adverse pregnancy outcomes.
In a case report published in the Iranian Journal of Neonatology, the researchers demonstrated how advanced genetic testing helped diagnose Tay-Sachs disease, a rare inherited disorder, even when routine prenatal ultrasound does not show major abnormalities.
The study, titled “A Rare Case of Antenatally Diagnosed Tay-Sachs Disease,” describes the case of a 30-year-old woman who was 19 weeks pregnant and had a significant family history of unexplained childhood illnesses and deaths. Two of her previous daughters had died at 11 months and five years of age, while another daughter had developed seizures and global developmental delay.
Despite the concerning family history, routine prenatal ultrasound did not reveal any major abnormalities. Given the history of consanguinity and previous children with suspected metabolic or neurodegenerative conditions, clinicians pursued genetic evaluation.
Whole-exome sequencing (WES) of both parents, followed by Sanger sequencing of the foetus, identified disease-causing variants in the HEXA gene associated with Tay-Sachs disease.
Redcliffe Labs researchers explained thatTay-Sachs disease is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the HEXA gene. When a child inherits disease-causing variants from both parents, production of the lysosomal enzyme beta-hexosaminidase A declines. This results in the accumulation of certain fatty substances in nerve cells and can lead to progressive and life-threatening neurological damage in affected children.
Family history can provide an important diagnostic clue
According to the researchers, the case highlights the limitations of relying on prenatal imaging alone when an inherited disorder is suspected.
They said that although prenatal ultrasound remains an essential part of pregnancy care, some genetic conditions may not produce detectable structural abnormalities at the time of scanning.
In such cases, they said, a detailed family history can provide a vital clinical clue and help determine whether further genomic investigation is warranted.
This may be particularly relevant for families with a history of unexplained childhood deaths, seizures, developmental delay, recurrent pregnancy or infant loss, known or suspected inherited disease, or consanguineous marriage.
The researchers encourage clinicians to incorporate family history assessment into routine prenatal care to improve early diagnosis of inherited conditions.
“Many rare inherited disorders may not be detectable through routine prenatal ultrasound alone. A detailed family history can provide important clinical clues, while advanced genomic testing can help identify the underlying genetic cause,” said Dr Himani Pandey, Lab Head – Genomics, Redcliffe Labs, and corresponding author of the study.
“In families with a previous history of unexplained childhood illness or recurrent adverse pregnancy outcomes, timely genetic evaluation may support earlier diagnosis and more informed reproductive and clinical decision-making,” she added.
Aditya Kandoi, Founder and CEO of Redcliffe Labs, highlighted the importance of investing in research to improve understanding of rare and inherited conditions and strengthen the standard of care.
“Our aim is not only to make advanced diagnostics accessible, but also to contribute evidence that can help clinicians recognise conditions that may otherwise remain undiagnosed,” he said.
The Redcliffe Labs study noted that genomic testing can complement conventional prenatal investigations by providing additional information for suspected inherited disorders. Once a disease-causing variant is identified, targeted testing and genetic counselling can help clinicians assess the risk of recurrence in future pregnancies and support families in making informed reproductive choices.
Genomic investigations such as whole-exome sequencing, clinical exome sequencing, targeted genetic testing, Sanger sequencing, chromosomal microarray and other prenatal genetic investigations are increasingly being used to investigate rare, inherited and reproductive health conditions.
