DDX3X syndrome is a common cause of unexplained learning disability, most commonly (but not exclusively) found in girls. While there are only around 1,000 known cases of DDX3X syndrome in the world, researchers estimate that it accounts for 1–3% of all learning disability in females.
As well as its connection with learning disability and global development delay, the syndrome is also connected with other neurodevelopmental conditions such as autism, ADHD and language delays, according to Beth Buccini and Liz Berger, founders of the DDX3X Foundation.
The syndrome was discovered just 10 years ago in 2014, so until recently, very little was known about this rare condition. Researchers have since been working to better understand DDX3X syndrome, and there are now more than 130 scientific papers compared to just one in 2015.
DDX3X syndrome occurs when one of the two copies of the DDX3X gene loses its expected function. These genetic changes usually happen randomly at conception. Diagnosing DDX3X syndrome can therefore be done through genetic testing on DNA. In the UK, testing is available through the NHS Genomic Medicine Service.
DDX3X syndrome primarily affects females due to the gene’s location on the X-chromosome, however, there are a few known cases in males. The majority of known cases are females who have ‘de novo’ (not inherited) variants in DDX3X; however, male individuals have been reported with either de novo variants or inherited variants from unaffected mothers.
While everyone with the syndrome known about to date has some degree of learning disability, the range of disability is very broad, with some people able to communicate well, learn many skills and have independence, while others have major difficulties communicating and need more intense supervision and support.
Behavioural difficulties, sensory processing problems and delays to motor skills are also common among people with DDX3X syndrome.
Although motor delays appear to be ubiquitous, most individuals do learn to walk independently, and only a minority require assistive walking devices. Delays to motor skills are often caused by hypotonia, or low muscle tone, which is one of the most frequently reported features of DDX3X syndrome.1
Sensory sensitivity is also a common feature of the syndrome, including hypersensitivities, hyposensitivities, and sensory seeking. Experts say this should therefore be assessed in all individuals with DDX3X syndrome to guide therapeutic recommendations.1
Autism and ADHD are also common among people with DDX3X syndrome, and DDX3X syndrome is emerging as one of the most common genetic causes of autism in females.1 Researchers believe behavioural difficulties are likely closely linked to autism and sensory issues.
Other symptoms of DDX3X syndrome include:
However, it is important to note that not everyone with DDX3X syndrome will have the same symptoms, and the symptoms can range from mild to severe depending on the individual.
There is no ‘cure’ for DDX3X syndrome as the genetic changes take place during a baby’s formation and development. However, there are many ways to manage DDX3X syndrome which can improve quality of life, as Beth and Liz explain: “The disorder presents on a spectrum and patients require massive amounts of therapy to help improve their condition including but not limited to occupational therapy, physical therapy, and speech therapy.”
Most individuals with DDX3X syndrome will need specialist educational support, while some will require behavioural therapy to help manage behaviours of distress and improve social skills.
Experts say primary care with specific monitoring is “vital” for people with DDX3X syndrome, as there are many associated features that should be closely monitored.1 This care may be best delivered by a developmental paediatrician, as they can identify potential syndrome-related features, including early signs of puberty, hearing problems, skin abnormalities, recurrent infections and hypothyroidism, referring where appropriate.
Research on DDX3X syndrome is ongoing, and scientists are working hard to understand it better and find new treatments and management options. In the meantime, early diagnosis and a comprehensive care planning can make a big difference in a child’s development and quality of life. While research is still fairly limited, it is vital that families and caregivers are given the support they need to manage the condition effectively.
For more information and support, please visit www.ddx3x.org or www.ddx3xsupportuk.co.uk.
