Rare Gastroenterology News

Disease Profile

Goldberg-Shprintzen megacolon 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

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.

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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)

Goldberg-Shprintzen syndrome; GOSHS

Categories

Congenital and Genetic Diseases; Digestive Diseases; Ear, Nose, and Throat Diseases;

Summary

Goldberg-Shprintzen megacolon syndrome (GOSHS) is a very rare genetic condition characterized by a swollen, irritated colon (megacolon); characteristic facial features; a small head, and intellectual disability.[1] Most people with GOSHS also are born with Hirschsprung disease, a condition in which the colon is missing nerve cells, leading to intestinal blockage.[2] Some patients with this condition have a defect in the iris of the eye (coloboma), brain and other central nervous system abnormalities, an opening in the roof of the mouth (cleft palate) and short stature. This condition is caused by changes (mutations) in the KIAA1279 (also known as K1F1BPgene, and appears to be inherited in an autosomal recessive pattern.[2][3] GOSHS is diagnosed based on the signs and symptoms and through genetic testing. Treatment is based on the symptoms and may include surgery.[4] This condition has been described in only about 15 individuals to date, and the long-term outlook for people with GOSHS is unclear.

Symptoms

The symptoms of Goldberg-Shprintzen megacolon syndrome vary from individual to individual. Some people may be more severely affected than others and not everyone with GOSHS will have the same symptoms.

The most common features of this condition are: 
Hirschsprung disease (a birth defect in which the colon does not work correctly due to missing nerve cells)
characteristic facial features
-wide-spaced eyes
-small head
-unusual eyebrows and hair
intellectual/learning disability

Other features may include a defect in the iris of the eye (coloboma), short stature, incomplete closure of the roof of the mouth (cleft palate), low muscle tone, and seizures.[1][4] 

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
Aganglionic megacolon
Enlarged colon lacking nerve cells
0002251
Cleft palate
Cleft roof of mouth
0000175
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Short stature
Decreased body height
Small stature

[ more ]

0004322
Specific learning disability
0001328
30%-79% of people have these symptoms
Iris coloboma
Cat eye
0000612
Muscular hypotonia
Low or weak muscle tone
0001252
Ptosis
Drooping upper eyelid
0000508
5%-29% of people have these symptoms
Bifid scrotum
Cleft of scrotum
0000048
Finger syndactyly
0006101
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Hypospadias
0000047
Macrotia
Large ears
0000400
Pachygyria
Fewer and broader ridges in brain
0001302
Pointed chin
Pointy chin
Small pointed chin
Witch's chin

[ more ]

0000307
Seizure
0001250
Sloping forehead
Inclined forehead
Receding forehead

[ more ]

0000340
Sparse and thin eyebrow
Thin, sparse eyebrows
0000535
Sparse scalp hair
Reduced/lack of hair on scalp
Scalp hair, thinning
Sparse, thin scalp hair
sparse-absent scalp hair

[ more ]

0002209
Ventriculomegaly
0002119
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
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance
0000007
Blue sclerae
Whites of eyes are a bluish-gray color
0000592
Bulbous nose
0000414
Clinodactyly
Permanent curving of the finger
0030084
Congenital onset
Symptoms present at birth
0003577
Corneal erosion
Damage to outer layer of the cornea of the eye
0200020
Corneal ulceration
0012804
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Everted lower lip vermilion
Drooping lower lip
Outward turned lower lip

[ more ]

0000232
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Global developmental delay
0001263
Highly arched eyebrow
Arched eyebrows
Broad, arched eyebrows
High, rounded eyebrows
High-arched eyebrows
Thick, flared eyebrows

[ more ]

0002553
Hypoplasia of the brainstem
Small brainstem
Underdeveloped brainstem

[ more ]

0002365
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion

[ more ]

0000327
Low-set ears
Low set ears
Lowset ears

[ more ]

0000369
Megalocornea
Enlarged cornea
0000485
Polymicrogyria
More grooves in brain
0002126
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge

[ more ]

0000426
Short neck
Decreased length of neck
0000470
Short philtrum
0000322
Small hand
Disproportionately small hands
0200055
Sparse hair
0008070
Synophrys
Monobrow
Unibrow

[ more ]

0000664
Tapered finger
Tapered fingertips
Tapering fingers

[ more ]

0001182
Telecanthus
Corners of eye widely separated
0000506
Thick eyebrow
Bushy eyebrows
Dense eyebrow
Heavy eyebrows
Prominent eyebrows
Thick eyebrows

[ more ]

0000574
Thick vermilion border
Full lips
Increased volume of lip
Plump lips
Prominent lips
Thick lips

[ more ]

0012471
Wide inter

Cause

Goldberg-Shprintzen megacolon syndrome is caused by a genetic change (mutation) in the KIAA1279 gene.[3]

Diagnosis

The diagnosis of Goldberg-Shprintzen megacolon syndrome is made when an individual has a specific pattern of signs and symptoms seen in this condition. Genetic testing of the KIAA1279 gene can also help confirm the diagnosis.[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

    There is no specific treatment for Goldberg-Shprintzen megacolon syndrome. Surgery may be done to treat Hirschsprung disease. Other treatment is aimed at preventing or managing the symptoms and complications associated with this syndrome.[1][4]

    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

      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

        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          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.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Goldberg-Shprintzen megacolon syndrome. Click on the link to view a sample search on this topic.

            References

            1. Drévillon L, Megarbane A, Demeer B, Matar C, Benit P, Briand-Suleau A, Bodereau V, Ghoumid J, Nasser M, Decrouy X, Doco-Fenzy M, Rustin P, Gaillard D, Goossens M, Giurgea I. KBP-Cytoskeleton Interactions Underlie Developmental Anomalies in Goldberg-Shprintzen Syndrome. Hum Mol Genet. Feb 19, 2013; https://www.ncbi.nlm.nih.gov/pubmed/23427148.
            2. Salehpour S, Hashemi-Gorji F, Miryounesi M. Association of a novel nonsense mutation in KIAA1279 with Goldberg-Shprintzen syndrome. Ir Jl Child Neur. Winter, 2017; 11(1):70-74. https://www.ncbi.nlm.nih.gov/pubmed/28277559.
            3. Goldberg-Shprintzen syndrome; GOSHS. Online Mendelian Inheritance in Man (OMIM). Updated 8/7/2014; https://www.omim.org/entry/609460.
            4. Dafsari HS, Byrne S, Lin JP, Pitt M, Jongbloed JD, Flinter F, Jungbluth H. Goldberg-Shprintzen megacolon syndrome with associated sensory motor axonal neuropathy. Am J Med Genet. Jun 2015; 167(6):1300-1304. https://www.ncbi.nlm.nih.gov/pubmed/25846562.

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