What are the other Names for this Condition? (Also known as/Synonyms)
- Dwarfism, Cortical Thickening of Tubular Bones and Transient Hypocalcemia
- Hypoparathyroidism-Retardation-Dysmorphism (HRD) Syndrome
- KCS (Kenny-Caffey Syndrome)
What is Kenny-Caffey Syndrome? (Definition/Background Information)
- Kenny-Caffey Syndrome (KCS) is a rare congenital disorder caused by mutation(s) in the TBCE or FAM111A gene. It is characterized by growth retardation and thickening of long bones in the limbs
- There are two types of KCS:
- Type I Kenny-Caffey Syndrome: It is caused by mutation in the TBCE gene; it is inherited in an autosomal recessive fashion
- Type II Kenny-Caffey Syndrome: It is caused by mutation in the FAM111A gene; it is inherited in an autosomal dominant fashion
- A positive family history of the disorder and having parents who are blood relatives (such as first cousins) are major risk factors for developing Kenny-Caffey Syndrome
- In addition to growth retardation, Kenny-Caffey Syndrome can result in low birth weight, bone and skull abnormalities, short stature, as well as hypocalcemia (low serum calcium levels)
- A physical examination, evaluation of symptoms, assessment of family medical history, examination of prominent bones using X-rays, and molecular genetic testing are often useful in making an accurate diagnosis of KCS
- There is currently no cure for Kenny-Caffey Syndrome. However, calcium and vitamin D supplements may help the affected individuals manage the symptoms of the condition better
- The prognosis of Kenny-Caffey Syndrome is determined by the severity of the disorder. Approximately, one-third of the children born with KCS succumb by early infancy, due to the various complications and bone deformities that arise from the disorder
- Presently, Kenny-Caffey Syndrome is a genetic disorder that cannot be prevented. However, pre-pregnancy screening, especially among blood-related couples, may help in planning for a child. It can also provide an understanding of the potential risks involved with respect to KCS
Who gets Kenny-Caffey Syndrome? (Age and Sex Distribution)
- Kenny-Caffey Syndrome is an uncommon genetic disorder, occurring at a frequency of less than 1:1,000,000
- The manifestation of the condition occurs at birth or during early infancy
- The syndrome occurs without any racial, ethnic, or gender bias. However, it has been reported that Middle-Eastern and Arabian Gulf populations show a higher incidence of KCS
What are the Risk Factors for Kenny-Caffey Syndrome? (Predisposing Factors)
The risk factors for being diagnosed with Kenny-Caffey Syndrome include:
- A family history of the disorder
- Having consanguineous parents (parents who are closely blood-related)
- Of Middle-Eastern or Arabian Gulf heritage
It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.
Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.
What are the Causes of Kenny-Caffey Syndrome? (Etiology)
Kenny-Caffey Syndrome is a genetic disorder that is caused by mutation(s) in the TBCE or FAM111A gene. The syndrome is of two types:
- Type I KCS is caused by a mutation in the TBCE gene. This gene codes for tubulin-specific chaperone E protein
- Also known as tubulin folding cofactor E, this protein is involved in the correct folding of beta-tubulins. The tubulins are organized into microtubules, and are part of the cytoskeleton, as well as the neuronal tubule network
- A mutation in this gene may lead to improper folding, and therefore, a disarray in the cytoskeletal organization, possibly resulting in the symptoms of Type 1 Kenny-Caffey Syndrome
- TBCE mutation is inherited in an autosomal recessive manner. An affected individual inherits one defective copy from each parent
- Type II KCS is caused by a mutation in the FAM111A gene. This gene codes for the protein known as family with sequence similarity 111, member A
- This protein is present in the nucleus, and interacts with the proliferating cell nuclear antigen or PCNA. PCNA is an important factor in DNA replication
- When the FAM111A gene is mutated, DNA replication is impaired, causing the symptoms associated with Type 2 Kenny-Caffey Syndrome
- FAM111A mutation is inherited in an autosomal dominant manner. Typically, one inherits the disease from an affected parent
Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children, born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).
Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.
What are the Signs and Symptoms of Kenny-Caffey Syndrome?
The signs and symptoms of Kenny-Caffey Syndrome common to both types 1 and 2, may include the following:
- Short stature, small hands and feet
- Thick bones with narrower central cavity
- Low blood calcium level; high blood phosphate level
- Iron deficiency anemia
- Transient low serum parathyroid hormone (PTH)
- Deep-set eyes
- Absence of pores within skull bones
The signs and symptoms specific to KCS type 1 may include:
- Abnormally small head
- Facial abnormalities such as:
- Up-slanting eyes
- Extremely thin lips
- Under-developed jaw
- Flat nasal bridge
- Liver disease in the neonatal stages
- Neutropenia or low levels of neutrophils (a type of white blood cells)
- Susceptibility to repeated infections
- Abnormal teeth development
- Abnormal and under-developed nails
- Mental retardation, to varying degrees
The signs and symptoms specific to KCS type 2 may include:
- Abnormally large head
- Abnormally small eyes
- Retinal calcification
- Congenital cataract
How is Kenny-Caffey Syndrome Diagnosed?
The following tests and examinations can assist in the diagnosis of Kenny-Caffey Syndrome:
- A thorough physical examination and assessment of symptoms
- Evaluation of the individual’s personal and family medical history
- X-ray studies to check for skeletal abnormalities: The key diagnostic features of KCS include a thickened external layer of long bones with narrowing central cavity, and an absence of small cavities within the skull bone
- Eye examination to check for eye defects/abnormalities, such as, congenital cataract and retinal calcification (characteristics of type II Kenny-Caffey Syndrome)
- Blood tests to check levels of the following parameters:
- Parathyroid hormone
- Molecular genetic testing to identify mutation in the TBCE or FAM111A gene; this can help confirm the diagnosis
Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.
What are the possible Complications of Kenny-Caffey Syndrome?
The following complications may develop in individuals affected by Kenny-Caffey Syndrome:
- Secondary hypothyroidism, which can lead to nervousness, muscle cramps, headaches, and memory loss (due to hypoparathyroidism)
- Liver malfunction in neonatal stages
- Multiple episodes of seizures
- Tooth decay
- Social isolation causing additional stress
How is Kenny-Caffey Syndrome Treated?
The treatment measures for Kenny-Caffey Syndrome are geared towards managing and providing relief from the symptoms, since there is no cure for this syndrome. Often, a coordinated effort from medical professionals belonging to different fields of expertise is required.
The following treatment options may be considered:
- Vitamin D and calcium supplements for low calcium levels
- Iron supplements for anemia
- Physiotherapy to help improve movement
- Surgery for cataract repair
- Dental procedures to repair abnormal teeth development
- Psychotherapy for stress and depression, if required
How can Kenny-Caffey Syndrome Be Prevented?
Kenny-Caffey Syndrome is a genetic condition, and therefore, there are no methods or guidelines available to prevent its occurrence.
- Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
- If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
- Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders such as KCS
Regular medical screening at periodic intervals with tests and physical examinations are crucial, and are highly recommended.
What is the Prognosis of Kenny-Caffey Syndrome? (Outcomes/Resolutions)
- Kenny-Caffey Syndrome is a genetic condition that requires lifelong monitoring and management
- Approximately 33% of the children born with KCS, die before or during early infancy from the complications that develop
- Complications, such as multiple episodes of seizures and skeletal deformities, may reduce the quality of life of the affected individual
Additional and Relevant Useful Information for Kenny-Caffey Syndrome:
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