Temtamy syndrome - Rare Immunology News

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Disease Profile

Temtamy syndrome

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US Estimated

Europe Estimated

Age of onset

Neonatal

ICD-10

Q87.8

Inheritance

Temtamy syndrome is inherited in an autosomal recessive manner.^[1] Like most genes, the C12orf57 gene comes in a pair (two copies). One copy of the gene is inherited from each parent. When a syndrome is inherited in an autosomal recessive manner, a person must have a pathogenic variant in both copies of the gene to have the syndrome. People who have a change in only one copy of the C12orf57 gene are carriers of Temtamy syndrome. Carriers typically do not have signs or symptoms of the syndrome.

When two carriers of Temtamy syndrome have children together, for each child there is a:

25% chance to inherit both changed copies of the C12orf57 gene, meaning the child will have Temtamy syndrome
50% chance to inherit one changed copy of the C12orf57 gene, meaning the child will be a carrier of Temtamy syndrome like each of the parents
25% chance to inherit both working copies of the C12orf57 gene, meaning the child will not have Temtamy syndrome and will not be a carrier of the syndrome

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)

Dysmorphism, corpus callosum agenesis and colobomas; Craniofacial dysmorphism with ocular coloboma absent corpus callosum and aortic dilatation

Summary

Temtamy syndrome is a developmental neurological disorder, meaning that it affects the way the brain is formed and how well it functions. In most cases, the bundle of nerve fibers (the corpus callosum) that connects the two sides of the brain is partially or completely missing. Other symptoms may include seizures, changes in the size or function of the eyes, heart problems, intellectual disability, and developmental delay. The syndrome appears to be more common in people from the Middle East, especially Saudi Arabia.^[1]^[2]^[3]

Temtamy syndrome is caused by genetic changes (pathogenic variants or mutations) in the C12orf57 gene. The syndrome is inherited in an autosomal recessive manner. Diagnosis is based on observing symptoms of the syndrome and the results of brain imaging. The diagnosis can be confirmed with genetic testing. Treatment for Temtamy syndrome may include medications to treat seizures, as well as therapies to help manage developmental delays.^[1]^[2]^[3]

Symptoms

Temtamy syndrome may affect the development of the brain, eyes, heart, and facial features. Children with Temtamy syndrome typically look different than other children. They may have a long face, widely-spaced eyes (hypertelorism), a large nose, and a small chin (micrognathia). Some children with Temtamy syndrome have relatively large heads (macrocephaly). These facial features may be present from birth. Other physical features of the syndrome may include having short fingers and toes (brachydactyly), bowed legs, or flat feet (pes planus).^[1]^[2]^[3]

People with Temtamy syndrome may have differences in the brain that can be seen on brain imaging. The most common feature is having a part of the brain, called the corpus callosum, that is smaller than expected, completely absent, or may be unusually thick. The corpus callosum is the bundle of nerves fibers that allows information to easily and quickly travel from one side of the brain to the other (between the left and right hemisphere). Problems in the development of the white matter of the brain may also be present. The white matter is the part of the brain made up of nerve fibers and myelin. Myelin forms a fatty, protective layer around nerve fibers, insulating the fibers so nerve signals pass through quickly.^[1]^[2]^[3]

Other neurological symptoms of Temtamy syndrome can include seizures and intellectual disability. Children with Temtamy syndrome may have low muscle tone (hypotonia) and they may meet milestones such as sitting up or walking later than other children do (developmental delay). Some children with Temtamy syndrome have autism.^[1]^[2]^[3]

Temtamy syndrome can also cause changes in the eyes, including changes in the tissues that form the eye (coloboma). Some people with Temtamy syndrome have one or both eyes that are smaller than expected (microphthalmia). These changes of the eyes may affect vision. Some people with Temtamy syndrome are born with heart problems because the heart did not form correctly.^[1]^[2]^[3]

The signs and symptoms of Temtamy syndrome can vary from person to person, even among members of the same family. This is a concept called variable expressivity.^[2]

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
Aplasia/Hypoplasia of the corpus callosum		0007370
Brachydactyly	Short fingers or toes	0001156
Chorioretinal coloboma	Birth defect that causes a hole in the innermost layer at the back of the eye	0000567
Global developmental delay		0001263
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Iris coloboma	Cat eye	0000612
Short toe	Short toes Stubby toes [ more ]	0001831
30%-79% of people have these symptoms
Aortic aneurysm	Bulge in wall of large artery that carries blood away from heart	0004942
Coarse facial features	Coarse facial appearance	0000280
Convex nasal ridge	Beaked nose Beaklike protrusion Hooked nose Polly beak nasal deformity [ more ]	0000444
Dolichocephaly	Long, narrow head Tall and narrow skull [ more ]	0000268
Genu varum	Outward bow-leggedness Outward bowing at knees [ more ]	0002970
Long face	Elongation of face Increased height of face Increased length of face Vertical elongation of face Vertical enlargement of face Vertical overgrowth of face [ more ]	0000276
Low-set ears	Low set ears Lowset ears [ more ]	0000369
Macrocephaly	Increased size of skull Large head Large head circumference [ more ]	0000256
Micrognathia	Little lower jaw Small jaw Small lower jaw [ more ]	0000347
Pes planus	Flat feet Flat foot [ more ]	0001763
5%-29% of people have these symptoms
Abnormal palate morphology	Abnormality of the palate Abnormality of the roof of the mouth [ more ]	0000174
Clinodactyly of the 5th finger	Permanent curving of the pinkie finger	0004209
Facial asymmetry	Asymmetry of face Crooked face Unsymmetrical face [ more ]	0000324
Joint hyperflexibility	Joints move beyond expected range of motion	0005692
Microphthalmia	Abnormally small eyeball	0000568
Telecanthus	Corners of eye widely separated	0000506
Thick lower lip vermilion	Increased volume of lower lip Plump lower lip Prominent lower lip [ more ]	0000179
Percent of people who have these symptoms is not available through HPO
Agenesis of corpus callosum		0001274
Aortic regurgitation		0001659
Autosomal recessive inheritance		0000007
Dental crowding	Crowded teeth Dental overcrowding Overcrowding of teeth [ more ]	0000678
Downslanted palpebral fissures	Downward slanting of the opening between the eyelids	0000494
Frontal bossing		0002007
Generalized hypotonia	Decreased muscle tone Low muscle tone [ more ]	0001290
Highly arched eyebrow	Arched eyebrows Broad, arched eyebrows High, rounded eyebrows High-arched eyebrows Thick, flared eyebrows [ more ]	0002553
Hip dislocation	Dislocated hips Dislocation of hip [ more ]	0002827
Hypoplasia of teeth		0000685
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Intellectual disability, mild	Mental retardation, borderline-mild Mild and nonprogressive mental retardation Mild mental retardation [ more ]	0001256
Lens luxation	Dislocated lens	0012019
Long philtrum		0000343
Lop ear		0000394
Myopia	Close sighted Near sighted Near sightedness Nearsightedness [ more ]	0000545
Seizure		0001250
Short 2nd toe	Short second toe	0001885
Talipes equinovarus	Club feet Club foot Clubfeet Clubfoot [ more ]	0001762
Ventriculomegaly		0002119

Cause

Temtamy syndrome is caused by genetic changes (pathogenic variants or mutations) in the C12orf57 gene. This gene provides each cell with instructions to make a protein that is thought to be important in the development of the brain, eyes, heart, and face. When there are pathogenic variants in both copies of the C12orf57 gene, not enough working protein is made, or possibly no working protein is made. Without enough of this protein the brain, eyes, heart, and face do not form properly. However, the exact function of the C12orf57 gene is not completely understood.^[1]^[2]

Diagnosis

Temtamy syndrome may be suspected when a baby or child has symptoms of the syndrome including intellectual disability, developmental delay, problems with the eyes or heart, distinctive facial features, or seizures. Brain imaging such as an MRI may show changes in the way the corpus callosum or white matter of the brain developed.^[3] Because Temtamy syndrome is so rare and many of its features are common to other syndromes, most children are diagnosed when they have a genetic test called whole exome sequencing. This test is used to look for genetic changes (mutations or pathogenic variants) in every gene of the body, including the C12orf57 gene.^[2]^[3]

Treatment

Unfortunately, there is no cure for Temtamy syndrome. Treatment is aimed at managing the symptoms of the syndrome. These treatment options may include surgeries to treat heart and eye problems and medications to treat seizures. Speech, occupational, and physical therapies may be important to allow children with Temtamy syndrome to reach their full potentials. Developmental delays may be helped by early intervention programs. Additional help in school may also be required, as most children with Temtamy syndrome have intellectual disability.^[1]^[3]

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
Differential diagnoses include muscle-eye-brain disease, Peters-plus, Walker-Warburg, Aicardi, Donnai-Barrow, and Baraitser-Winter syndromes (see these terms). 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

National Organization of Disorders of the Corpus Callosum
PMB 363
18032-C Lemon Drive
Yorba Linda, CA 92886
Telephone: +1-714-747-0063
Fax: +1-714-693-0808
E-mail: [email protected]
Website: https://nodcc.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.

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 Temtamy syndrome. Click on the link to view a sample search on this topic.

References

Sherr E. Temtamy syndrome. Orphanet. August 2014; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=1777.
Temtamy Syndrome; TEMTYS. Online Mendelian Inheritance in Man. March 28, 2017; https://www.omim.org/entry/218340.
Alrakaf L, Al-Owain MA, Busehail M, Alotaibi MA, Monies D, Aldhalaan HM, Alhashem A, Al-Hassnan ZN, Rahbeeni ZA, Murshedi FA, Ani NA, Al-Maawali A, Ibrahim NA, Abdulwahab FM, Alsagob M, Hashem MO, Ramadan W, Abouelhoda M, Meyer BF, Kaya N, Maddirevula S, and Alkuraya FS. Further delineation of Temtamy syndrome of corpus callosum and ocular abnormalities. American Journal of Medical Genetics. Part A. March 2018; 176(3):715-721. https://www.ncbi.nlm.nih.gov/pubmed/29383837.
Temtamy Syndrome. Hereditary Ocular Disease Database. The University of Arizona Health Sciences; https://disorders.eyes.arizona.edu/handouts/temtamy-syndrome. Accessed 4/5/2018.

Rare Immunology News

Rare Immunology News

Rare Immunology News

Neonatal

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

Treatment

Related diseases

Organizations

Organizations Supporting this Disease

Learn more

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.