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Disease Profile

Nicolaides-Baraitser 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

-

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)

NCBRS; Intellectual disability-sparse hair-brachydactyly syndrome

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Nicolaides-Baraitser syndrome (NCBRS) is a very rare condition characterized by severe intellectual disability and various physical features. Signs and symptoms may include seizures, short stature, sparse hair, distinctive facial characteristics, short fingers and toes (brachydactyly), and prominent joints in the fingers and toes (interphalangeal joints). Features of the condition can worsen over time. NCBRS is caused by changes (mutations) in the SMARCA2 gene and is inherited in an autosomal dominant manner. All cases reported to date have been sporadic, occurring in people with no family history of NCBRS.[1]

Symptoms

Nicolaides-Baraitser syndrome (NCBRS) is typically characterized by intellectual disability, seizures, short stature, sparse hair, distinctive facial features, short fingers and toes (brachydactyly), and prominent joints of the fingers and toes (called interphalangeal joints). Some features of the condition may vary among affected people.[1]

All people with NCBRS have intellectual disability. In most cases it is severe, but in some cases it may be moderate or mild. Language is particularly limited, with at least 30% of affected people never developing speech. Major motor milestones such as sitting and walking are usually not very delayed. People with NCBRS are often happy and friendly, but may have temper tantrums or periods of aggression. Some people have some symptoms of autism spectrum disorder. Epilepsy occurs in about 2/3 of affected people. The type of seizures that occur can vary.[1]

Facial characteristics are usually not recognized in younger affected people. They may include a triangular-shaped face; prominent eyelashes; a nose with a broad base, thick nostrils, and upturned tip; a broad philtrum; and wide mouth. The palpebral fissures (width of the eyes) are sometimes narrow and/or downslanting. As people with NCBRS age, the amount of subcutaneous fat tissue tends to decrease, making the skin below the eyes sagging and wrinkled, especially at the cheeks when smiling. However, some affected people retain full cheeks. Facial characteristics typically become more pronounced with increasing age. In some affected adults, the lower third of the face becomes markedly broad.[1]

Sparse scalp hair is a major feature of NCBRS and is present in almost all affected people. It often gradually worsens with age, but in some people it improves over time. Skin is usually wrinkled and more noticeable in the distal limbs. Teeth may be widely spaced, and eruption of teeth (baby or adult) may be delayed. While the hands and feet usually appear normal at birth, the interphalangeal joints become prominent in the majority of affected people. Bone age can vary, and osteoporosis is not uncommon.[1]

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
Abnormality of the metacarpal bones
Abnormality of the long bone of hand
0001163
Alopecia
Hair loss
0001596
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Aphasia
Difficulty finding words
Losing words
Loss of words

[ more ]

0002381
Brachydactyly
Short fingers or toes
0001156
Dysphasia
0002357
Echolalia
Echoing another person's speech
0010529
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
Global developmental delay
0001263
High, narrow palate
Narrow, high-arched roof of mouth
Narrow, highly arched roof of mouth

[ more ]

0002705
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Joint dislocation
Joint dislocations
Recurrent joint dislocations

[ more ]

0001373
Long philtrum
0000343
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Mutism
Inability to speak
Muteness

[ more ]

0002300
Short palm
0004279
Smooth philtrum
0000319
Sparse hair
0008070
Specific learning disability
0001328
Thick nasal alae
0009928
Thin vermilion border
Decreased volume of lip
Thin lips

[ more ]

0000233
Triangular face
Face with broad temples and narrow chin
Triangular facial shape

[ more ]

0000325
Wide mouth
Broad mouth
Large mouth

[ more ]

0000154
30%-79% of people have these symptoms
Abnormal hair pattern
Abnormal distribution of hair
0010720
Blepharophimosis
Narrow opening between the eyelids
0000581
Broad distal phalanx of finger
Broad outermost finger bone
0009836
Clubbing of toes
0100760
Cryptorchidism
Undescended testes
Undescended testis

[ more ]

0000028
Curly eyelashes
0007665
Eczema
0000964
Epileptic spasm
0011097
Excessive wrinkled skin
0007392
Generalized non-motor (absence) seizure
Brief seizures with staring spells
0002121
Highly arched eyebrow
Arched eyebrows
Broad, arched eyebrows
High, rounded eyebrows
High-arched eyebrows
Thick, flared eyebrows

[ more ]

0002553
Long eyelashes
Increased length of eyelashes
Unusually long eyelashes

[ more ]

0000527
Narrow nasal bridge
Nasal Bridge, Narrow
Nasal bridge, thin
Narrow bridge of nose

[ more ]

0000446
Sandal gap
Gap between 1st and 2nd toes
Gap between first and second toe
Increased space between first and second toes
Sandal gap between first and second toes
Wide space between 1st, 2nd toes
Wide space between first and second toes
Wide-spaced big toe
Widely spaced 1st-2nd toes
Widely spaced first and second toes
Widened gap 1st-2nd toes
Widened gap first and second toe

[ more ]

0001852
Scoliosis
0002650
Severe short stature
Dwarfism
Proportionate dwarfism
Short stature, severe

[ more ]

0003510
Short palpebral fissure
Short opening between the eyelids
0012745
Status epilepticus
Repeated seizures without recovery between them
0002133
Wide intermamillary distance
Wide-spaced nipples
Widely spaced nipples
Widely-spaced nipples

[ more ]

0006610
5%-29% of people have these symptoms
Abnormality of cardiovascular system morphology
0030680
Abnormality of epiphysis morphology
Abnormal shape of end part of bone
0005930
Accelerated skeletal maturation
Advanced bone age
Early bone maturation

[ more ]

0005616
Delayed skeletal maturation
Delayed bone maturation
Delayed skeletal development

[ more ]

0002750
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hernia
0100790
1%-4% of people have these symptoms
Short stature
Decreased body height
Small stature

[ more ]

000432

Cause

Nicolaides-Baraitser syndrome (NCBRS) is caused by mutations in the SMARCA2 gene, which is located on the small arm of chromosome 9. All mutations that have been identified in affected people have been either missense mutations or in-frame deletions.

There may be some correlations between specific types of mutations and some of the features that result (called genotypephenotype correlations), but more studies are needed to draw definitive conclusions.[1]

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.

Organizations Supporting this Disease

    Social Networking Websites

      Organizations Providing General Support

        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

        • Genetics Home Reference (GHR) contains information on Nicolaides-Baraitser syndrome. This website is maintained by the National Library of Medicine.

          In-Depth Information

          • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
          • 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.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Nicolaides-Baraitser syndrome. Click on the link to view a sample search on this topic.

            References

            1. Sousa SB, Hennekam RC; Nicolaides-Baraitser Syndrome International Consortium. Phenotype and genotype in Nicolaides-Baraitser syndrome. Am J Med Genet C Semin Med Genet. September, 2014; 166C(3):302-314.
            2. Sousa SB, et. al. Nicolaides-Baraitser syndrome: Delineation of the phenotype. Am J Med Genet A. August, 2009; 149A(8):1628-1640.
            3. Omar Abdul-Rahman. Nicolaides-Baraitser Syndrome. GeneReviews. October 15, 2015; https://www.ncbi.nlm.nih.gov/books/NBK321516/.

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