Detecting Fragile X Syndrome

In 2017, a man in Delhi, affected by autism, underwent his first DNA blood test at the age of 40. He tested positive for Fragile X Syndrome (FXS). This is caused by changes in a gene called FMR1 which make an important protein (FMRP). This protein is required for brain development.

Largely undetected in India

It was in 1991, 14 years after that man was born, that the mutation was discovered and named FRAXA by three American geneticists — Ben Oostra, David Nelson and Stephen Warren. They found that it was the leading inherited cause of autism worldwide.

Three decades ago, there was no primary knowledge of this among healthcare professionals. However, even after the discovery of FMR1, the lack of awareness and appropriate training to diagnose FXS in time prevails everywhere. In India, the lack of adequate screening and diagnostic facilities, the stigma attached to mental health, the absence of surveys in community settings, and bare minimum hospital data based on clinical experience have all kept FXS largely undetected.

According to a 2019 review paper of the Advanced Centre for Evidence-Based Child Health, established by PGIMER, Chandigarh, under the aegis of the Indian Council of Medical Research, “there is an under-recognition of the genetic disorder due to delay in diagnosis at young age and the lack of uniform application of validated, accessible and affordable diagnostic tools.” It is estimated there are 4,00,000 individuals who have been identified with mutated FMRI in India and 40 lakh undiagnosed carriers of the gene.

According to Centers for Disease Control and Prevention (CDC), one in 7,000 males and one in 11,000 females are affected with FXS. FXS is the leading inherited cause of autism in 4% of the population worldwide. The CDC estimates that one in 259 women and one in 800 men carry Fragile X. A mother who is a carrier has a 50% chance of passing the mutated gene to her children, who will either be carriers or have FXS. Men who are carriers do not pass the pre-mutation to their sons, but only daughters, who become carriers. This knowledge is crucial and the numbers are critical and demand attention, according to Professor Sumantra Chattarji, senior neurobiologist at the National Centre for Biological Sciences in Bengaluru. His research is focused on correcting the powerful emotional symptoms of FXS. It helps empower parents with information about babies in whom the FMR1 shuts down the production of FMRP.

Shalini Kedia, who founded the Fragile X Society of India in 2003 as a support system for families impacted with FXS, says that it is every woman’s right to make an informed choice of becoming a special mother. Studies suggest a high effect of consanguineous parenting on FXS prevalence.

Timely detection

The simplest tool for timely detection is a DNA test. In the U.S., FXS testing is mandatory for every child diagnosed with autism. This helps parents plan their family better. In India, doctors often fail to appropriately guide women who have fertility issues, late pregnancies, opt for IVF with donor eggs, or donate embryo for surrogacy.

Experts suggest an overhaul of the MBBS curriculum to include a detailed chapter on FXS and more government-organised Continuing Medical Education programmes for practising healthcare professionals so that FXS is treated as a major public health concern. Mass awareness and an additional test in the list of pregnancy and prenatal and neonatal tests for other chromosomal abnormalities (such as Down Syndrome) will be beneficial. But the majority of people are either not aware of the FXS test or cannot afford it. Tests are done in major government hospitals and in a few private labs and cost between ₹4,500 and ₹7,500.

People must understand that autism triggered by FXS is a behavioural condition. The symptoms are learning difficulty, speech delay, aggressive behaviour, hyperactivity, attention deficit, fear of the unfamiliar, sensory processing disorders and problems in motor skills. These cannot be cured, but early therapy can improve the individual’s quality of life.

The National Policy for Treatment of Rare Diseases, 2017, was limited by challenges in implementation. This year, the government introduced the National Policy for Rare Diseases Act. It calls for systematic epidemiological studies on incidence and prevalence of rare diseases. Without naming FXS directly, it recommends prenatal tests for lesser-known single-gene and other genetic disorders. This is profound as the dialogue on rare diseases has to be kept open, even during the pandemic. Or else, it will leave all those who are trying to cope feel even more vulnerable and isolated.

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Printable version | Oct 25, 2021 11:38:18 PM |

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