What are the other Names for this Condition? (Also known as/Synonyms)

• Gracile Bone Dysplasia
• KCS II
• Kenny-Caffey Syndrome, Autosomal Dominant Form

What is Kenny-Caffey Syndrome Type 2? (Definition/Background Information)

• Kenny-Caffey Syndrome Type 2 (KCS-2) is a rare congenital disorder caused by mutation(s) in the FAM111A gene. It is characterized by growth retardation and thickening of long bones in the limbs. The disorder 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 Type 2
• A low birth weight, hypoparathyroidism at birth, bone and skull abnormalities, low serum calcium levels, abnormal facial features, calcification of retina, and cataracts at birth, are some of the other symptoms of Kenny-Caffey Syndrome Type 2
• A physical examination, evaluation of symptoms, assessment of family medical history, eye exam, examination of prominent bones using X-rays, and molecular genetic testing are often useful in making an accurate diagnosis of KCS Type 2
• There is currently no cure for Kenny-Caffey Syndrome Type 2. However, calcium and vitamin D supplements may help the affected individuals manage the symptoms of the condition better. It is also possible to repair cataracts through surgery
• The prognosis of Kenny-Caffey Syndrome Type 2 is determined by the severity of the disorder. The complications and bone deformities that arise from the disorder may be present throughout one’s life and affect the quality of life
• Presently, Kenny-Caffey Syndrome Type 2 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-2 better

Who gets Kenny-Caffey Syndrome Type 2? (Age and Sex Distribution)

• Kenny-Caffey Syndrome Type 2 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 2? (Predisposing Factors)

The following are some risk factors for developing Kenny-Caffey Syndrome Type 2:

• 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 2? (Etiology)

Kenny-Caffey Syndrome Type 2 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 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 Type 2?

The signs and symptoms of Kenny-Caffey Syndrome Type 2 may include:

• Short stature, small hands and feet
• Thick bones with narrower central cavity
• Delayed closure of the anterior fontanel (the soft, membrane-covered area on the top and front of a child’s skull)
• Abnormally large head; abnormally small eyes
• Eye defects including:
  • Swelling of the optic disk due to leakage of cerebrospinal fluid
  • Farsightedness
  • Retinal calcification
  • Congenital cataract
• Seizures
• Episodes of low serum calcium level; high serum phosphate level
• Iron deficiency anemia
• Transient hypoparathyroidism (low levels of serum parathyroid hormone)

How is Kenny-Caffey Syndrome Type 2 Diagnosed?

The following tests and examinations can assist in the diagnosis of Kenny-Caffey Syndrome Type 2:

• 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
• Blood tests to check levels of the following parameters:
  • Calcium
  • Magnesium
  • Phosphate
  • Iron
  • Parathyroid hormone
• Molecular genetic testing to identify mutation in the FAM111A 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 2?

The following complications may develop in individuals affected by Kenny-Caffey Syndrome Type 2:

• Dwarfism
• Secondary hypothyroidism, which can lead to nervousness, muscle cramps, headaches, and memory loss (due to hypoparathyroidism)
• Multiple episodes of seizures
• Abnormal teeth development
• Social isolation causing additional stress

How is Kenny-Caffey Syndrome Type 2 Treated?

The treatment measures for Kenny-Caffey Syndrome Type 2 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
• Lenses for correction of vision defects
• Dental procedures to repair abnormal teeth development
• Psychotherapy for stress and depression, if required

How can Kenny-Caffey Syndrome Type 2 be Prevented?

Kenny-Caffey Syndrome Type 2 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 2

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 2? (Outcomes/Resolutions)

• Kenny-Caffey Syndrome Type 2 is a genetic condition that requires lifelong monitoring and management
• 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 2:

Kenny-Caffey Syndrome Type 1 (KCS-1) is a rare congenital disorder caused by mutation(s) in the TBCE gene. It is an autosomal recessive condition.