Goldberg-Shprintzen megacolon syndrome

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Disease Profile

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US Estimated

Europe Estimated

Age of onset

Infancy

ICD-10

Q87.8

Inheritance

Goldberg-Shprintzen megacolon syndrome (GOSHS) is inherited in an autosomal recessive pattern.[] All individuals inherit two copies of each gene. In order to have GOSHS, a person must have a mutation in both copies of the responsible gene (KIAA1279) in each cell. There is nothing either parent can do, before or during pregnancy, to cause a child to have this.

People with autosomal recessive conditions inherit one mutation from each of their parents. The parents, who each have one mutation, are known as carriers. Carriers of an autosomal recessive disorder typically do not have any signs or symptoms (they are unaffected). When two carriers of an autosomal recessive condition have children, each child has a:

• 25% (1 in 4) chance to have the disorder
• 50% (1 in 2) chance to be an unaffected carrier like each parent
• 25% (1 in 4) chance to be unaffected and not be a carrier

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

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.

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.

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

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.

Not applicable

Other names (AKA)

Goldberg-Shprintzen syndrome; GOSHS

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 H irschsprung 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 K1F1BP) gene, 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]

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet

Main differential diagnoses include Mowat-Wilson (MWS) and Baraitser-Winter syndromes. Different facial characteristics (thick, horizontal eyebrows and uplifted earlobes with a central depression), presence of seizures and hypospadias, and absence of polymicrogyria and oligodontia distinguish MWS. Key overlapping features with Baraitser-Winter syndrome include intellectual disability, microcephaly, congenital ptosis, high-arched eyebrows, ocular coloboma and short stature; however, Hirschsprung disease, congenital heart defects, and urogenital malformations have not been reported in this syndrome.

Visit the Orphanet disease page for more information.

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

Children's Craniofacial Association
13140 Coit Road Suite 517
Dallas, TX 75240
Toll-free: 1-800-535-3643
Telephone: +1-214-570-9099
Fax: +1-214-570-8811
E-mail: [email protected]
Website: https://ccakids.org/
FACES: The National Craniofacial Association
PO Box 11082
Chattanooga, TN 37401
Toll-free: 800-332-2373
Telephone: 423-266-1632
E-mail: [email protected]
Website: https://www.faces-cranio.org/
World Craniofacial Foundation
P.O. Box 515838
Dallas, TX 75251-5838
Toll-free: 800-533-3315
Telephone: 972-566-6669
Fax: 972-566-3850
E-mail: [email protected]
Website: https://www.worldcf.org/

Organizations Providing General Support

Association of Gastrointestinal Motility Disorders (AGMD)
140 Pleasant Street
Lexington, MA 02421
Telephone: +1-781-275-1300
E-mail: [email protected]
Website: https://www.agmdhope.org/
International Foundation for Functional Gastrointestinal Disorders (IFFGD)
3015 Dunes West Blvd. Suite 512
Mount Pleasant, SC 29466
Telephone: +1-414-964-1799
Website: https://iffgd.org/

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

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.
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.
Goldberg-Shprintzen syndrome; GOSHS. Online Mendelian Inheritance in Man (OMIM). Updated 8/7/2014; https://www.omim.org/entry/609460.
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.

Rare Hematology News

Rare Hematology News

Rare Hematology News

Infancy

Q87.8

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

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.

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.

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

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

Treatment

Related diseases

Organizations

Organizations Supporting this Disease

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

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.

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