Rare Endocrinology News

Disease Profile

Severe intellectual disability-progressive spastic diplegia syndrome

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

G80.1

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.

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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)

Intellectual disability, autosomal dominant 19; CTNNB1-related intellectual disability; CTNNB1 syndrome

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Severe intellectual disability-progressive spastic diplegia syndrome is a rare condition that has been described in a few people with severe intellectual disability . Other signs and symptoms include progressive microcephaly (very small head); ataxia (lack of coordination); spasticity; and/or skin, hair and mild facial anomalies. It is caused by changes (mutations) in the CTNNB1 gene and it is inherited in an autosomal dominant fashion. Treatment is based on the signs and symptoms present in each person.[1][2][3][4]

Symptoms

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
80%-99% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Motor delay
0001270
Muscular hypotonia of the trunk
Low muscle tone in trunk
0008936
Poor speech
0002465
Spasticity
Involuntary muscle stiffness, contraction, or spasm
0001257
30%-79% of people have these symptoms
Congenital microcephaly
0011451
Developmental regression
Loss of developmental milestones
Mental deterioration in childhood

[ more ]

0002376
5%-29% of people have these symptoms
Abnormal temper tantrums
0025160
Aggressive behavior
Aggression
Aggressive behaviour
Aggressiveness

[ more ]

0000718
Autistic behavior
0000729
Broad nasal tip
Broad tip of nose
Broad, upturned nose
Increased breadth of nasal tip
Increased breadth of tip of nose
Increased width of nasal tip
Increased width of tip of nose
Nasal tip, broad
Nasal tip, wide
Wide tip of nose

[ more ]

0000455
Delayed CNS myelination
0002188
Hypermetropia
Farsightedness
Long-sightedness

[ more ]

0000540
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Long philtrum
0000343
Low hanging columella
0009765
Myopia
Close sighted
Near sighted
Near sightedness
Nearsightedness

[ more ]

0000545
Self-injurious behavior
Self-injurious behaviour
0100716
Sleep disturbance
Difficulty sleeping
Trouble sleeping

[ more ]

0002360
Smooth philtrum
0000319
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Syringomyelia
Fluid-filled cyst in spinal cord
0003396
Tethered cord
0002144
Thin upper lip vermilion
Thin upper lip
0000219
Underdeveloped nasal alae
Underdeveloped tissue around nostril
0000430
Ventriculomegaly
0002119
1%-4% of people have these symptoms
Exudative vitreoretinopathy
0030490
Generalized hypopigmentation
Fair skin
Pale pigmentation

[ more ]

0007513
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Optic atrophy
0000648
Seizure
0001250
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
High palate
Elevated palate
Increased palatal height

[ more ]

0000218
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Neurological speech impairment
Speech disorder
Speech impairment
Speech impediment

[ more ]

0002167
Spastic diplegia
0001264

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Social Networking Websites

  • CTNNB1 syndrome is a closed Facebook group for Severe intellectual disability-progressive spastic diplegia syndrome.

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.

Where to Start

  • Unique is a source of information and support for families and individuals affected by rare chromosome disorders. Click on the link to view information about Severe intellectual disability-progressive spastic diplegia syndrome.

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. Dubruc E, Putoux A, Labalme A, Rougeot C, Sanlaville D & Edery P. A new intellectual disability syndrome caused by CTNNB1 haploinsufficiency. Am. J. Med. Genet. 2014; 164:1571-1575. https://www.medscape.com/medline/abstract/24668549. Accessed 10/12/2015.
  2. Mental retardation, autosomal dominant 19. OMIM. July 24, 2014; https://omim.org/entry/615075. Accessed 10/12/2015.
  3. Tucci V & cols. Dominant beta-catenin mutations cause intellectual disability with recognizable syndromic features. J. Clin. Invest. 2014; 124:1468-1482. https://www.ncbi.nlm.nih.gov/pubmed/24614104. Accessed 10/12/2015.
  4. Kuechler A & cols. De novo mutations in beta-catenin (CTNNB1) appear to be a frequent cause of intellectual disability: expanding the mutational and clinical spectrum. Hum Genet. January, 2015; 134(1):97-109. https://www.ncbi.nlm.nih.gov/pubmed/25326669. Accessed 10/12/2015.