GATAD2B-associated neurodevelopmental disorder

Title

Other Names:

Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome

Categories:

Congenital and Genetic Diseases

Summary Summary

GATAD2B-associated neurodevelopmental disorder (GAND) affects the way the brain develops. Symptoms of GAND include moderate to severe intellectual disability, poor speech development, and large head size. Other signs and symptoms may include low muscle tone in children (childhood hypotonia), feeding problems, heart problems and shared facial features. Because so few cases have been described in the medical literature, it is difficult to know how this condition changes over time. GAND is caused by a GATAD2B gene that is absent or not working correctly. It usually occurs in a family for the first time due to a new genetic change (de novo) and may be inherited in an autosomal dominant pattern. GAND is diagnosed based on the symptoms, a clinical exam and genetic testing. Treatment is focused on managing the symptoms.^[1]^[2]^[3]

Last updated: 8/27/2020

Symptoms Symptoms

The following list includes the most common signs and symptoms in people with GATAD2B-associated neurodevelopmental disorder (GAND). These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Symptoms may include:^[1]^[2]

Intellectual disability
Developmental delay
Speech disorder (apraxia)
Low muscle tone in childhood (hypotonia)
Large head size (macrocephaly)
Crossed eyes (strabismus)
Feeding difficulties

Less common symptoms of GAND may include heart problems and seizures. People with GAND tend to share similar facial features such as a broad forehead and wide-set eyes.

Many of the features of GAND are present at birth. It is not well understood how GAND changes over the course of an individual's lifetime.

Last updated: 8/27/2020

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 55 |

Medical Terms	Other Names	Learn More: HPO ID
30%-79% of people have these symptoms
Abnormality of the cerebral white matter		0002500
Broad forehead	Increased width of the forehead Wide forehead [ more ]	0000337
Broad nasal tip	Broad, upturned nose Increased breadth of tip of nose Increased breadth of nasal tip Broad tip of nose Wide tip of nose Nasal tip, wide Nasal tip, broad Increased width of tip of nose Increased width of nasal tip [ more ]	0000455
Delayed myelination		0012448
Facial grimacing		0000273
Fine hair	Fine hair shaft Fine hair texture Thin hair shaft Thin hair texture [ more ]	0002213
Generalized non-motor (absence) seizure	Brief seizures with staring spells	0002121
Global developmental delay		0001263
Hyperactivity	More active than typical	0000752
Hyperopic astigmatism		0000484
Infantile muscular hypotonia	Decreased muscle tone in infant	0008947
Intellectual disability, severe	Mental retardation, severe Early and severe mental retardation Severe mental retardation [ more ]	0010864
Long fingers		0100807
Poor speech		0002465
Short philtrum		0000322
Strabismus	Squint eyes Squint Cross-eyed [ more ]	0000486
Thin upper lip vermilion	Thin upper lip	0000219
Wide mouth	Broad mouth Large mouth [ more ]	0000154
5%-29% of people have these symptoms
Autistic behavior		0000729
Broad distal phalanx of finger	Broad outermost finger bone	0009836
Chronic constipation	Infrequent bowel movements	0012450
Deeply set eye	Deep set eye Deep-set eyes Sunken eye [ more ]	0000490
Depressed nasal bridge	Depressed bridge of nose Flat bridge of nose Flat nasal bridge Flat, nasal bridge Flattened nasal bridge Low nasal bridge Low nasal root [ more ]	0005280
Epicanthus	Eye folds Prominent eye folds [ more ]	0000286
Feeding difficulties	Feeding problems Poor feeding [ more ]	0011968
Frontal bossing		0002007
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Hypospadias		0000047
Inappropriate laughter		0000748
Incomprehensible speech		0002546
Intrauterine growth retardation	Prenatal growth deficiency Prenatal growth retardation [ more ]	0001511
Joint laxity	Joint instability Lax joints Loose-jointedness Loosejointedness [ more ]	0001388
Long palpebral fissure	Broad opening between the eyelids Long opening between the eyelids Wide opening between the eyelids [ more ]	0000637
Long toe	Increased length of toes Long toes [ more ]	0010511
Low frustration tolerance		0000744
Lower limb spasticity		0002061
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Narrow palpebral fissure	Small opening between the eyelids	0045025
Obsessive-compulsive trait	Obsessive-compulsive traits	0008770
Optic nerve hypoplasia		0000609
Periorbital fullness	Puffiness around eye	0000629
Self-mutilation	Deliberate self-harm Self mutilation [ more ]	0000742
Sleep disturbance	Difficulty sleeping Trouble sleeping [ more ]	0002360
Tics	Tic disorder	0100033
Upslanted palpebral fissure	Upward slanting of the opening between the eyelids	0000582
Widely-spaced maxillary central incisors	Gap between upper front teeth Wide gap between upper central incisors Widely spaced upper incisors [ more ]	0001566
1%-4% of people have these symptoms
Language impairment		0002463
Sparse hair		0008070
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Blepharophimosis	Narrow opening between the eyelids	0000581
Hypermetropia	Farsightedness Long-sightedness [ more ]	0000540
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Neonatal hypotonia	Low muscle tone, in neonatal onset	0001319
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 2/1/2021

Cause Cause

GATA2DB-associated neurodevelopmental disorder is caused by a GATAD2B gene that is not working correctly. DNA changes known as pathogenic variants are responsible for making genes work incorrectly or sometimes, not at all.^[4]

Last updated: 8/27/2020

Inheritance Inheritance

GATAD2B-associated neurodevelopmental disorder (GAND) can be inherited in an autosomal dominant pattern. All individuals inherit two copies of each gene. Autosomal means the gene is found on one of the numbered chromosomes found in both sexes. Dominant means that only one altered copy of a gene is necessary to have the condition. The alteration can be inherited from either parent. Sometimes an autosomal dominant condition occurs because of a new genetic alteration (de novo) and there is no history of this condition in the family. This is often the case for GAND.^[1]

Each child of an individual with an autosomal dominant condition has a 50% or 1 in 2 chance of inheriting the alteration and the condition. Typically, children who inherit a dominant alteration will have the condition, but they may be more or less severely affected than their parent. Sometimes a person may have a gene alteration for an autosomal dominant condition and show no signs or symptoms of the condition.

In rare cases, it may be inherited from a parent who has a genetic variant in the GATAD2B gene in some of his or her cells but not all of them (mosaic). A parent who is mosaic for a genetic variant in the GATAD2B gene usually does not have any symptoms of GAND.^[3]

Last updated: 8/27/2020

Diagnosis Diagnosis

A diagnosis of GATAD2B-associated neurodevelopmental disorder is made based on the symptoms and a clinical exam and is confirmed by genetic testing.^[1]^[2]

Last updated: 8/27/2020

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

Treatment for GATAD2B-associated neurodevelopmental disorder is focused on managing the symptoms.

Specialists involved in the care of someone with GATAD2B-associated neurodevelopmental disorder may include:^[1]^[5]

Developmental specialist
Neurologist
Cardiologist
Ophthalmologist
Speech language pathologist

Last updated: 8/27/2020

Statistics Statistics

The exact number of people with GATAD2B-associated neurodevelopmental disorder is unknown. The information on this condition is based on individual case reports in the medical literature.

Last updated: 8/27/2020

Do you have updated information on this disease? We want to hear from you.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from MedlinePlus Genetics.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

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References References

Shieh C, Jones N, Vanle B, et al. GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder. Genet Med. 2020. 2020; 22(5):878-888. https://pubmed.ncbi.nlm.nih.gov/31949314.
Vera G, Sorlin A, Delplancq G, et al. Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND) [published online ahead of print, 2020 Jul 17]. Eur J Med Genet. 2020; 63(10):104004. https://pubmed.ncbi.nlm.nih.gov/32688057.
Kaur P, Mishra S, Rajesh SM, Girisha KM, Shukla A. GATAD2B-related intellectual disability due to parental mosaicism and review of literature. Clin Dysmorphol. 2019; 28(4):190-194. https://pubmed.ncbi.nlm.nih.gov/31205050.
Willemsen MH, Nijhof B, Fenckova M, et al. GATAD2B loss-of-function mutations cause a recognisable syndrome with intellectual disability and are associated with learning deficits and synaptic undergrowth in Drosophila. J Med Genet. August, 2013; 50(8):507-14. http://www.ncbi.nlm.nih.gov/pubmed/23644463. Accessed 10/28/2015.
Pierson TM, Otero MG, Grand K, et al. The NuRD complex and macrocephaly associated neurodevelopmental disorders. Am J Med Genet C Semin Med Genet. 2019;181(4):548-556. 2019; 181(4):548-556. https://pubmed.ncbi.nlm.nih.gov/31737996.