Severe mental retardation, impaired speech, strabismus, grimacing face, long finger syndrome

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Classification according to ICD-10
Q87.8 Other specified congenital malformation syndromes, not elsewhere classified
ICD-10 online (WHO version 2019)

The severe intellectual disability, impaired speech, strabismus, grimacing face, long finger syndrome is an autosomal dominant hereditary disease . It is caused by a mutation of GATAD2B (locus: 1q21.3), a subunit of the methyl-CpG-binding protein-1 complex, and was described in 2013. According to the gene causing the disease, the disease is also known as GATAD2B-Associated Neurodevelopmental Disorder (abbr .: GAND ). Another designation is intellectual disability, autosomal dominant 18 (English: Mental retardation, autosomal dominant 18; abbreviation: MRD18 ).

Spread and cause

The prevalence of the diseases is less than 1 in 1,000,000. It is inherited dominantly and manifests itself in infancy . A publication was published in January 2020 describing 50 cases.

The disease is caused by a mutation in the GATAD2B gene (locus: 1q21.3). The disease usually occurs de novo , i.e. H. spontaneously, and is very rarely inherited , for example when there is a mosaic and the parent is symptom-free. In animal experiments (using Drosophila ), damage to the orthologous gene resulted in a restriction in the animals' ability to learn and an altered morphology of the synapses . A total of 41 variants of GATAD2B have been described so far, which determine the extent and scope of the symptoms.

Clinical manifestations

The symptoms are diverse, do not occur in the same way in all those affected and, based on current knowledge, include the following points:

The extent of verbal communication skills varies from affected individual to affected individual, albeit at a very low level: The spectrum ranges from the absence of any spoken language to a vocabulary of 30 words at the age of 3 years and 8 months.

All affected individuals have in common that they reach the early childhood development milestones with a delay, if at all. The range in which those affected learn to sit varies from 9.5 months to 19.9 months with an average of 14.7 months. Those affected only learn to walk at an average age of 33.1 months, with a range from 20.5 months to 45.7 months. At the same time, it should be mentioned that not all those affected learn to walk and even if they do, their gait is very shaky and unstable.

Research methods, treatment and prevention

A clear diagnosis is made through a genetic analysis of the GATAD2B gene.

There is no known curative treatment.

There are no indications that the spontaneous genetic change can be prevented or provoked by environmental, nutritional or lifestyle factors. However, if one of the parents wears this change (also known as a germ cell mosaic ), the risk is increased.

Individual evidence

  1. ↑ orpha.net: Severe intellectual disabilities -impaired speech-strabismus-grimacing face-long finger syndrome , here online ; last viewed on May 10, 2020.
  2. ↑ omim.org: GATA ZINC FINGER DOMAIN-CONTAINING PROTEIN 2B; GATAD2B , here online ; last viewed on May 10, 2020.
  3. ↑ a b c d e f g h i Marjolein H Willemsen, Bonnie Nijhof, Michaela Fenckova, Willy M Nillesen, Ernie MHF Bongers: GATAD2B loss-of-function mutations cause a recognizable syndrome with intellectual disability and are associated with learning deficits and synaptic undergrowth in Drosophila . In: Journal of Medical Genetics . tape 50 , no. 8 , August 2013, ISSN  0022-2593 , p. 507-514 , doi : 10.1136 / jmedgenet-2012-101490 ( bmj.com [accessed May 10, 2020]).
  4. ↑ a b c d e f g h i j k l The Undiagnosed Diseases Network, Christine Shieh, Natasha Jones, Brigitte Vanle, Margaret Au: GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder . In: Genetics in Medicine . tape 22 , no. 5 , May 2020, ISSN  1098-3600 , p. 878-888 , doi : 10.1038 / s41436-019-0747-z ( nature.com [accessed May 10, 2020]).
  5. ↑ What is GAND? Retrieved May 10, 2020 (English).
  6. ↑ omim.orf: # 615074 , online here
  7. ↑ a b c GATAD2B syndrome information brochure of the organization "Unique | Understanding Rare Chromosome and Gene Disorders", accessed on May 10, 2020.
  8. ↑ orpha.net: Brief description of the disease (English) , online here ; last viewed on May 10, 2020.