About DHX30

DHX30 Syndrome is an ultra-rare disorder caused by a harmful genetic mutation. 

This content has been reviewed and verified by Dr. Ali Rosenberg, PhD, as of February 2026.

Clinical Basics
Genetics Basics
Diagnosis

Clinical Basics

What is DHX30 Syndrome, DHX30-related Neurodevelopmental Disorders, or NEDMIAL?

DHX30 Syndrome is an ultra-rare genetic disorder caused by pathogenic (harmful) mutations in a gene called DHX30 on chromosome 3 [3]. 

This condition is called a neurodevelopmental disorder because it is a behavioral and cognitive disorder that is typically diagnosed during a child’s early development and involves significant difficulties in the acquisition and execution of specific intellectual, motor, language, or social functions [8].

NEDMIAL is another name for this disorder and stands for “Neurodevelopmental Disorder characterized with severe Motor Impairment and Absent Language,” but NEDMIAL is not typically used by the community because each person with this disorder is unique and some individuals can learn to speak and walk [1-3].

What are the symptoms of DHX30 Syndrome? 

Symptoms and their severity can vary between individuals, and often include [1-3]: 

  • Global developmental delay

  • Speech impairment 

  • Low muscle tone (hypotonia)

  • Intellectual disability 

  • Seizures

  • Eye misalignment

  • Joint hypermobility

  • Feeding challenges

  • Sleep disturbances 

  • Autistic features/behavioral differences 

What is the long-term prognosis of those affected by a DHX30 mutation?

Long-term outcomes are still being studied because DHX30 Syndrome is a fairly new diagnosis [3]. What we know so far is that most known individuals require lifelong supportive care, and that the level of independence can vary between individuals. Developmental progress is possible, especially with early intervention. Because each person with DHX30 Syndrome is different, it is difficult to compare the exact journey of each person to another, even for individuals who both have the same DHX30 variant. 

How common is DHX30 Syndrome?

DHX30 Syndrome is considered ultra-rare. As of early 2026, our peer organization DHX30 United is aware of nearly 170 individuals worldwide. As genetic sequencing becomes more common, more individuals will be diagnosed. 

Can the DHX30 mutation be treated today?

No cure for the DHX30 mutation exists. Currently, treatment focuses on supportive and symptomatic care, and our peer organization DHX30 United overviews many of these therapies. Our Foundation is dedicated to DHX30 research that will help us better understand DHX30 Syndrome and develop treatments for all people with a DHX30 mutation. 

Genetics Basics

What happens when DHX30 is mutated? 

Generally, variants in the DHX30 gene prevent the resulting DHX30 protein from being able to do its normal job in the body [1-3]. Read more below to learn about DHX30’s normal role in the cell and how different kinds of mutations cause different kinds of problems.

What does the DHX30 gene normally do?

Every cell in the body needs to make proteins to carry out the cell’s functions, and our genes are the instructions for making all of those proteins. When a gene is turned into a protein, there is a middle step where the instructions the gene provides are temporarily copied, like a single recipe copied onto a notecard out of the whole cookbook. This “recipe” is called messenger RNA (mRNA). 

DHX30 is a type of RNA helicase protein. It is important, especially in brain cells, for helping certain mRNAs turn into proteins [1-3]. Using this analogy, DHX30 is responsible for working with a subset of mRNA “recipes” and making sure they are “read” properly.

Are there different types of mutations or variants in the DHX30 gene? 

Yes. When a “misspelling” or mutation (also known as a variant) occurs in the alphabet of our genetic sequence, it can be due to different types of mutations. Some examples of these different mutations include missense mutations, nonsense mutations, and frameshift mutations. For more detail, explore this explanation of types of mutations. 

A patient’s specific variants are typically notated on their genetic report. Recurrent DHX30 variants from publications include p.Arg782Trp (c.2344C>T) and p.Arg785Cys (c.2353C>T) [2,3]

How do different types of mutations affect DHX30 protein function?

Studies of DHX30 show that a certain amount of DHX30 protein is needed for cells to function normally, and this requires that the two copies of DHX30 in each person work properly. DHX30 Syndrome is an autosomal dominant condition, meaning  affected individuals have a mutation in one of their two DHX30 gene copies, which is enough to cause symptoms of DHX30 syndrome [1-3]. 

Loss-of-function mutations (typically nonsense, frameshift, and in-frame deletion variants) often result in a too-short nonfunctional version of  the protein. This is also called haploinsufficiency, where there is too little of the protein available to manage cell functions. Individuals with haploinsufficiency tend to have milder clinical symptoms in comparison to individuals with gain-of-functional mutations [2].  

Gain-of-function mutations (typically missense variants) usually create full-length abnormal proteins. In DHX30, these abnormal proteins are hypothesized to interfere with the function of the normal DHX30 protein. This is also called a dominant negative effect. This can result in a compounded scenario where not only are individuals with a gain-of-function mutation missing their second working copy of DHX30, but the mutated copy actively works against the existing normal copy. These individuals tend to have more severe clinical symptoms [2].

Diagnosis

How is DHX30 diagnosed?

Diagnosis can only be made through diagnostic genetic testing [2]. Whole Exome Sequencing or Whole Genome Sequencing is used because symptoms alone are not enough for a diagnosis- DHX30 Syndrome looks similar to numerous other neurodevelopmental disorders [1]. 

What is the cause of DHX30 Syndrome in a patient?

Individuals with DHX30 Syndrome have a pathogenic (or harmful) mutation in the DHX30 gene [2]. In most cases, a DHX30 mutation (also called a variant) occurs spontaneously and is not inherited from either parent [1,3]. This type of genetic change is called a de novo mutation, and happens randomly in either the egg, sperm, or sometime early in the life of the fetus. Nothing either parent did before or during pregnancy causes this change. Genetic mutations occur naturally and randomly. Some individuals may have inherited their DHX30 mutation from one parent who may not have shown any symptoms themselves. This short video entitled De Novo Variants, Inherited Variants, and Mosaicism explains de novo and inherited variants, as well as mosaicism (discussed below). 

How do I read and understand a genetic report? 

We recommend you confer with your medical geneticist or genetic counselor to understand your specific report. We’ve also linked the Children’s Hospital of Philadelphia’s guide as a resource.   

Can the DHX30 mutation be identified during pregnancy? 

Because a DHX30 mutation is ultra-rare and is not part of typical prenatal screening or testing, it is nearly impossible for parents to identify that their child could have a DHX30 variant. Even in inherited cases, the parent may not have had any symptoms that would suggest that a clinician search for the cause of this ultra-rare disorder [1,2]. Currently, the only method to identify a DHX30 mutation during pregnancy is to obtain a fetal sample through chorionic villus sampling (CVS) or amniocentesis and test using Whole Genome Sequencing or Whole Exome Sequencing.  

Can non-invasive prenatal screening (NIPS/NIPT) or typical prenatal or newborn screening tests find DHX30 during pregnancy?  

There are key distinctions between screening vs. diagnostic tests that all parents should understand in order to make informed decisions and so newborns can have a better chance at early treatment for any disease. Prenatal and newborn screening and testing are topics that Remy’s parents are passionate about and part of the reason they engaged Dr. Wendy Chung, Remy’s geneticist at Boston Children’s Hospital, and the creator of the GUARDIAN Study.

Screening Tests

  • Identify whether your child is at increased [9] risk for the condition(s) screened

  • Less expensive, less accurate

  • Prenatal testing on maternal blood sample

  • Post-birth testing on baby heel-stick blood sample or other tests 

  • Example test: NIPS or NIPT, a prenatal screening test, checks against a common list of genetic abnormalities. Ultra rare mutations, such as DHX30, are not on these screens 

Diagnostic Tests 

  • Provide a definitive “yes” or “no” diagnosis [9]

  • More accurate, more expensive 

  • Not an initial choice in prenatal and newborn screening

  • Prenatal testing on sample from chorionic villus sampling (cvs) or amniocentesis

  • Post-birth testing on a saliva swab or blood sample 

  • Example test: Whole Genome Sequencing (WGS) or Whole Exome Sequencing (WES), are diagnostic for mutations almost anywhere in the genome  

What is the sibling risk for DHX30 Syndrome?

For families who have had a child with a de novo DHX30 mutation, the chance that another child will have a variant is very low if the variant is not present in the parents. However, it is not zero: there is a possibility of “germline mosaicism,” where a parent unknowingly carries the DHX30 mutation only in some of their egg or sperm cells. For families whose child has an inherited variant, the risk of another child inheriting the same variant is high. 

Genetic counseling can provide information on each family’s own risk, and each case should be evaluated individually.

What role can IVF play in genetic conditions involving the DHX30 gene?

We recommend you speak with your doctor and genetic counselor to understand your specific situation.

Citations

  1. Lederbauer, et al. “RNA Helicases in Neurodevelopmental Disorders.” Frontiers in Molecular Neuroscience (2024): 1414949. DOI: 10.3389/fnmol.2024.1414949

  2. Mannucci, Ilaria, et al. “Genotype–Phenotype Correlations and Novel Molecular Insights into the DHX30-Associated Neurodevelopmental Disorders.” Genome Medicine 13 (2021): 90. DOI: 10.1186/s13073-021-00900-3

  3. Lessel, Davor, et al. “De Novo Missense Mutations in DHX30 Impair Global Translation and Cause a Neurodevelopmental Disorder.” The American Journal of Human Genetics 101 (2017): 716–724. DOI: 10.1016/j.ajhg.2017.09.014

  4. Antonicka, Hana, et al. “Mitochondrial RNA Granules Are Centers for Posttranscriptional RNA Processing and Ribosome Biogenesis.” Cell Reports 10 (2015): 920–932. DOI: 10.1016/j.celrep.2015.01.030

  5. Bosco, Bartolomeo, et al. “DHX30 as a Potential Vulnerability in Cancer Cells.” Cancers 13, no. 17 (2021): 4412. DOI: 10.3390/cancers13174412

  6. Dörner, Kerstin, and Maria Hondele. “The Story of RNA Unfolded: The Molecular Function of DEAD- and DExH-Box ATPases and Their Complex Relationship with Membraneless Organelles.” Annual Review of Biochemistry 93 (2024): 79–108. DOI: 10.1146/annurev-biochem-052521-121259

  7. Fiorenzani, Chiara, et al. “DEAD/DEAH-Box RNA Helicases Shape the Risk of Neurodevelopmental Disorders.” Trends in Genetics (2024). Advance online publication. DOI: 10.1016/j.tig.2024.12.006

  8. World Health Organization. “Mental Disorders.” World Health Organization Fact Sheet, 2025.https://www.who.int/news-room/fact-sheets/detail/mental-disorders 

  9. Labcorp Women's Health. “Screening and Diagnostic Tests: Know the Difference.” Labcorp Women's Health Fact Sheet, 2026.https://womenshealth.labcorp.com/patients/results/testing-vs-screening