Temtamy syndrome

Alternate names

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

Definition

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.

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.

Inheritance

Autosomal recessive inheritance, a 25% chance

Temtamy syndrome is inherited in an autosomal recessive manner. 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

Signs and 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).
• 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.
• 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.
• 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.
• 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.

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Aplasia/Hypoplasia of the corpus callosum
• Brachydactyly(Short fingers or toes)
• Chorioretinal coloboma(Birth defect that causes a hole in the innermost layer at the back of the eye)
• Global developmental delay
• Hypertelorism(Wide-set eyes)
• Intellectual disability(Mental deficiency)
• Iris coloboma(Cat eye)
• Short toe(Short toes)

30%-79% of people have these symptoms

• Aortic aneurysm(Bulge in wall of large artery that carries blood away from heart)
• Coarse facial features(Coarse facial appearance)
• Convex nasal ridge(Beaked nose)
• Dolichocephaly(Long, narrow head)
• Genu varum(Outward bow-leggedness)
• Long face(Elongation of face)
• Low-set ears(Low set ears)
• Macrocephaly(Increased size of skull)
• Micrognathia(Little lower jaw)
• Pes planus(Flat feet)

5%-29% of people have these symptoms

• Abnormal palate morphology(Abnormality of the palate)
• Clinodactyly of the 5th finger(Permanent curving of the pinkie finger)
• Facial asymmetry(Asymmetry of face)
• Joint hyperflexibility(Joints move beyond expected range of motion)
• Microphthalmia(Abnormally small eyeball)
• Telecanthus(Corners of eye widely separated)
• Thick lower lip vermilion(Increased volume of lower lip)

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.
• 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.

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.

Prognosis

• Many children who have Temtamy syndrome have seizures that are not managed well with medications. This can cause some children with the syndrome to lose skills that they once had (regress) or have worsening intellectual disability.
• Eye abnormalities may cause problems with vision, and vision may continue to worsen throughout life.
• In some cases, a baby or child may pass away due to complications such as complex heart problems. However, people with the syndrome can live into adulthood.

NIH genetic and rare disease info

• NIH info on Temtamy syndrome

Temtamy syndrome is a rare disease.

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