GENE GUIDE

DYNC1H1-Related Syndrome

This guide is not meant to take the place of medical advice. Please consult with your doctor about your genetic results and health care choices. This Gene Guide was last updated on 2024. As new information comes to light with new research we will update this page. You may find it helpful to share this guide with friends and family members or doctors and teachers of the person who has DYNC1H1-Related Syndrome.
a doctor sees a patient

DYNC1H1-related syndrome is also called Charcot-Marie-Tooth disease, Complex cortical dysplasia with other brain malformations, or Spinal muscular atrophy with lower extremity predominance. For this guide, we will be using the name DYNC1H1-related syndrome to encompass the wide range of variants observed in the people identified.

DYNC1H1-related syndrome happens when there are changes to the DYNC1H1 gene. These changes can keep the gene from working as it should.

Key Role

The DYNC1H1 gene plays a key role in the basic function of the cell.

Symptoms

Symptoms can vary widely. Because the DYNC1H1 gene is important in the development and function of brain cells, many people who have DYNC1H1-related syndrome have:

  • Neuromuscular issues
  • Intellectual disability
  • Autism
  • Seizures
  • Eye issues

People who have DYNC1H1-related syndrome have different types of genetic variants. This can affect which symptoms they have.

DYNC1H1-related syndrome is a genetic condition, which means that it is caused by variants in genes. Our genes contain the instructions, or code, that tell our cells how to grow, develop, and work. Every child gets two copies of the DYNC1H1 gene: one copy from their mother’s egg, and one copy from their father’s sperm. In most cases, parents pass on exact copies of the gene to their child. But the process of creating the egg or sperm is not perfect. A change in the genetic code can lead to physical issues, developmental issues, or both. 

Sometimes a spontaneous variant happens in the sperm, egg or after fertilization. When a brand new genetic variant happens in the genetic code is called a ‘de novo’ genetic variant. The child is usually the first in the family to have the genetic variant.

De novo variants can take place in any gene. We all have some de novo variants, most of which don’t affect our health. But because DYNC1H1 plays a key role in development, de novo variants in this gene can have a meaningful effect. 

Research shows that DYNC1H1-related syndrome is often the result of a de novo variant in DYNC1H1. Many parents who have had their genes tested do not have the DYNC1H1 genetic variant found in their child who has the syndrome. In some cases, DYNC1H1-related syndrome happens because the genetic variant was passed down from a parent.

Autosomal dominant conditions

GENE-related syndrome is an autosomal dominant genetic condition. This means that when a person has the one damaging variant in DYNC1H1 they will likely have symptoms of DYNC1H1-related syndrome. For someone with an autosomal dominant genetic syndrome, every time they have a child there is a 50 percent chance they pass on the same genetic variant and a 50 percent chance they do not pass on the same genetic variant.

Autosomal Dominant Genetic Syndrome

GENE / gene
GENE / gene
Genetic variant that happens in sperm or egg, or after fertilization
GENE / gene
Child with de novo genetic variant
gene / gene
Non-carrier child
gene / gene
Non-carrier child

Why does my child have a change in the DYNC1H1 gene?

No parent causes their child’s DYNC1H1-related syndrome. We know this because no parent has any control over the gene changes that they do or do not pass on to their children. Please keep in mind that nothing a parent does before or during the pregnancy causes this to happen. The gene change takes place on its own and cannot be predicted or stopped.

Each family is different. A geneticist or genetic counselor can give you advice on the chance that this will happen again in your family.

The risk of having another child who has DYNC1H1-related syndrome depends on the genes of both biological parents. 

  • If neither biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is on average 1 percent. This 1 percent chance is higher than the chance of the general population. The increase in risk is due to the very unlikely chance that more of the mother’s egg cells or the father’s sperm cells carry the same genetic variant. 
  • If one biological parent has the same genetic variant found in their child, the chance of having another child who has the syndrome is 50 percent. 

For a symptom-free brother or sister of someone who has DYNC1H1-related syndrome, the sibling’s risk of having a child who has DYNC1H1-related syndrome depends on the sibling’s genes and their parents’ genes. 

  • If neither parent has the same genetic variant causing DYNC1H1-related syndrome, the symptom-free sibling has a nearly 0 percent chance of having a child who would inherit DYNC1H1-related syndrome. 
  • If one biological parent has the same genetic variant causing DYNC1H1-related syndrome, the symptom-free sibling has a 50 percent chance of also having the same genetic variant. If the symptom-free sibling has the same genetic variant, their chance of having a child who has the genetic variant is 50 percent. 

For a person who has DYNC1H1-related syndrome, the risk of having a child who has the syndrome is about 50 percent.

As of 2024, at least 129 people with DYNC1H1-related syndrome have been described in medical research, whereas at least 187 people with DYNC1H1-related syndrome have been identified in the medical literature. The first case of DYNC1H1-related syndrome was described in 2011.

Appearance can vary. In a few cases, people who have DYNC1H1-related syndrome may look different.

Scientists and doctors have only just begun to study DYNC1H1-related syndrome. At this point, there are no medicines designed to treat the syndrome. A genetic diagnosis can help people decide on the best way to track the condition and manage therapies. Doctors can refer people to specialists for:

  • Physical exams and brain studies.
  • Genetics consults.
  • Development and behavior studies.
  • Other issues, as needed.

A developmental pediatrician, neurologist, or psychologist can follow progress over time and can help:

  • Suggest the right therapies. This can include physical, occupational, speech, or behavioral therapy.
  • Guide individualized education plans (IEPs).

Specialists advise that therapies for DYNC1H1-related syndrome should begin as early as possible, ideally before a child begins school. Surgery may be necessary for people who have issues with the roof of their mouth or severe curved spine. If seizures happen, consult a neurologist. There are many types of seizures, and not all types are easy to spot. To learn more, you can refer to resources such as the Epilepsy Foundation’s website: epilepsy.com/learn/types-seizures.

This section includes a summary of information from a review of major published articles that describe around 130 people who have DYNC1H1-related syndrome. It highlights how many people have different symptoms. To learn more about the review, see the Sources and references section of this guide.

Researchers think that the DYNC1H1 variant determines the clinical features that a person develops. There are two major categories of clinical features. The first category is central nervous system symptoms, such as brain defects, intellectual developmental disorder, and developmental and epileptic encephalopathy. The second category includes neuromuscular diseases, such as spinal muscular atrophy with lower extremity predominance and Charcot-Marie-Tooth, type 20.

Most DYNC1H1 variants are called missense variants. They result in a change in one amino acid in the DYNC1H1 protein.

People with DYNC1H1-related syndrome who have central nervous system issues often have intellectual disability and epilepsy. Central nervous system issues in DYNC1H1-related syndrome include; smaller than average head size, larger than average head size, and brain structure issues.

  • 54 out of 71 people had epilepsy (76 percent)
  • 67 out of 71 people had intellectual disability or developmental delay (94 percent)
76%
54 out of 71 people had epilepsy.
92%
67 out of 71 people had intellectual disability or developmental delay.

In people with central nervous system issues, it was common for them to have brain structure changes called pachygyria. Pachygyria is a brain structure formation issue in one part of the brain that makes that region abnormally dense. Some people have hypoplasia of the corpus callosum, in which a region of the brain called the corpus callosum does not form the way it should.

  • 45 out of 58 people had pachygyria (78 percent)
  • 15 out of 58 people had hypoplasia of the corpus callosum (26 percent)

People with DYNC1H1-related syndrome who had neuromuscular diseases did not often have intellectual disability or epilepsy, but they had lower limb muscle issues.

  • 5 out of 58 people had epilepsy (9 percent)
  • 14 out of 58 people had intellectual disability or developmental delay (24 percent)
9%
5 out of 58 people had epilepsy (9 percent).
24%
14 out of 58 people had intellectual disability or developmental delay.

Variants in the ‘stem domain’ of the DYNC1H1 protein are more often associated with neuromuscular conditions. Variants in the ‘motor domain’ of the DYNC1H1 protein are more often associated with central nervous system conditions. These clinical categorizations are not always separate, and people with a combination of neuromuscular features and central nervous system features have been reported in the medical literature.

Where can I find support and resources?

DYNC1H1 Association

Their mission is to create opportunities for research on DYNC1H1 with a constant drive towards low-risk, high reward treatments.

DYNC1H1 Gene Mutation Family Support Group

This group provides information and support to families affected by a DYNC1H1 mutation.

Simons Searchlight

Simons Searchlight is an online international research program, building an ever growing natural history database, biorepository, and resource network of over 175 rare genetic neurodevelopmental disorders. By joining their community and sharing your experiences, you contribute to a growing database used by scientists worldwide to advance the understanding of your genetic condition. Through online surveys and optional blood sample collection, they gather valuable information to improve lives and drive scientific progress. Families like yours are the key to making meaningful progress. To register for Simons Searchlight, go to the Simons Searchlight website at www.simonssearchlight.org and click “Join Us.”

Sources and References

The content in this guide comes from a published review about DYNC1H1-related syndrome. Below you can find details about the review, as well as a link to a summary.

  • Amabile S. et al. American Journal of Medical Genetics Part A, 182, 2049-2057, (2020). DYNC1H1-related disorders: A description of four new unrelated patients and a comprehensive review of previously reported variants – pubmed.ncbi.nlm.nih.gov/32656949
  • Chung, C. T., Lee, N. C., Fan, S. P., Hung, M. Z., Lin, Y. H., Chen, C. H., & Jao, T. (2023). DYNC1H1 variant associated with epilepsy: Expanding the phenotypic spectrum. Epilepsy & Behavior Reports, 21, 100580. https://pubmed.ncbi.nlm.nih.gov/36636459/
  • Ge, W. R., Fu, P. P., Zhang, W. N., Zhang, B., Ding, Y. X., & Yang, G. (2023). Case report: Genotype and phenotype of DYNC1H1-related malformations of cortical development: A case report and literature review. Frontiers in Neurology, 14, 1163803. https://pubmed.ncbi.nlm.nih.gov/37181555/

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