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Disease Profile

GATAD2B-associated neurodevelopmental disorder

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Infancy

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ICD-10

Q87.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

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

Categories

Congenital and Genetic Diseases

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]

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.

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.

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 ]

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]

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 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

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.

References

  1. 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.
  2. 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.
  3. 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.
  4. 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. https://www.ncbi.nlm.nih.gov/pubmed/23644463. Accessed 10/28/2015.
  5. 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.

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