What are the other Names for this Condition? (Also known as/Synonyms)
- KCS I
- Kenny-Caffey Syndrome, Autosomal Recessive Form
- Sanjad-Sakati Syndrome (SSS)
What is Kenny-Caffey Syndrome Type 1? (Definition/Background Information)
- Kenny-Caffey Syndrome Type 1 (KCS-1) is a rare congenital disorder caused by mutation(s) in the TBCE gene. It is characterized by growth retardation and thickening of long bones in the limbs. The disorder is inherited in an autosomal recessive fashion
- Since KCS-1 is a genetic disorder, having a positive family history is a major risk factor for being diagnosed with the disorder. Additionally, individuals with parents who are close blood relatives, may be at risk
- A low birth weight, hypoparathyroidism at birth, bone and skull abnormalities, small hands and feet, low serum calcium levels, and abnormal facial features are some of the other symptoms of Kenny-Caffey Syndrome Type 1
- 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 Type 1
- There is currently no cure for Kenny-Caffey Syndrome Type 1. However, calcium and vitamin D supplements may help the affected individuals manage the symptoms of the condition better
- The prognosis of Kenny-Caffey Syndrome Type 1 is determined by the severity of the disorder. Many 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 Type 1 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-1 better
Who gets Kenny-Caffey Syndrome Type 1? (Age and Sex Distribution)
- Kenny-Caffey Syndrome Type 1 is an extremely uncommon genetic disorder
- The manifestation of the condition mostly 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 Type 1? (Predisposing Factors)
The risk factors for being diagnosed with Kenny-Caffey Syndrome Type 1 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 Type 1? (Etiology)
Kenny-Caffey Syndrome Type 1 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
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).
What are the Signs and Symptoms of Kenny-Caffey Syndrome Type 1?
The signs and symptoms of Kenny-Caffey Syndrome Type 1 may include the following:
- Low birth weight
- Failure to thrive
- Short stature, small hands and feet
- Thick bones with narrower central cavity
- Low serum calcium level; high serum phosphate level
- Iron deficiency anemia
- Sustained, low levels of parathyroid hormone
- Facial abnormalities such as:
- Abnormally small head, narrow face
- Deep-set eyes, up-slanting eyes
- Extremely thin lips
- Under-developed jaw
- Flat nasal bridge, beaked nose
- Large ears, which may be floppy
- Liver disease in the neonatal stages
- Calcification of kidneys
- Neutropenia or low levels of neutrophils (a type of white blood cells)
- Susceptibility to repeated bacterial infections
- Under-developed and abnormal nails
- Tooth decay
- Low IQ, with varying degrees of intellectual disability
How is Kenny-Caffey Syndrome Type 1 Diagnosed?
The diagnosis of Kenny-Caffey Syndrome Type 1 is made based on the following tests and exams:
- 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
- Blood tests to check levels of the following parameters:
- Parathyroid hormone
- Liver enzymes
- Molecular genetic testing to identify mutation in the TBCE gene, which 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 Type 1?
The following complications may develop in individuals affected by Kenny-Caffey Syndrome Type 1:
- 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
- Abnormal teeth development
- Social isolation causing additional stress
How is Kenny-Caffey Syndrome Type 1 Treated?
The treatment measures for Kenny-Caffey Syndrome Type 1 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
- Dental procedures to repair abnormal teeth development
- Antibiotics treatment for neonates with pneumonia
- Psychotherapy for stress and depression, if required
How can Kenny-Caffey Syndrome Type 1 be Prevented?
Kenny-Caffey Syndrome Type 1 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 Type 1
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 Type 1? (Outcomes/Resolutions)
- Kenny-Caffey Syndrome Type 1 is a genetic condition that requires lifelong monitoring and management
- Many children born with KCS-1, 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 Type 1:
- While many reports use Kenny-Caffey Syndrome Type 1 and Sanjad-Sakati Syndrome (SSS) synonymously, some state that KCS-1 is different from SSS. Such reports inform that individuals with KCS-1 do not exhibit certain skeletal deformities, nor do they have any intellectual disability. However, both KCS-1 and SSS are caused by mutation(s) in the TBCE gene.
- Kenny-Caffey Syndrome Type 2 (KCS-2) is a rare congenital disorder caused by mutation(s) in the FAM111A gene. It is an autosomal dominant condition