Kleefstra syndrome (KS) occurs when there is a tiny piece of chromosome 9 missing or deleted.  An individual may also develop the disorder after a gene mutation or intragenic duplication.  People with Kleefstra syndrome have intellectual disability and other complex clinical and physical features. The affected gene is known as Euchromatic Histone Methyltransferase1 (EHMT1).  When there is disturbance or absence of the gene, it causes symptoms associated with the syndrome. Different symptoms may occur in persons who have KS and the variations may arise because of the extent or number of deleted or damaged part of the 9q34.3 region. Sometimes, people with almost same deletion size may have different symptoms. The life expectancy of people with Kleefstra syndrome isn’t well known because it is a recent diagnosis and there are no statistics doctors can rely on to show how long people with the disorder survive.

Although most cases of Kleefstra syndrome are de novo there are rare cases where a child inherits the 9q34.3 gene deletion from a parent who is not affected.  In this case, the parent is said to be mosaic meaning that he or she has deletion occurring in some cells while other cells are unaffected. KS may be reproduced and passed onto the children, but again this is a rare occurrence. About 75 percent of the documented incidents of Kleefstra syndrome are as a result of disruptions in Eu-HMTase1 while about 25 percent are as a result of deletions in 9q34.3 region of chromosome 9.

Kleefstra Syndrome Signs and Symptoms

Until recently, the severity and number of symptoms a child has was thought to be directly related to the size of deletion, however, it has now been known that it’s not the deletion size but the location where the breakage occurs within the chromosomal arm. More than one gene may be affected, and that’s the reason you find that people with Kleefstra syndrome have a variety of issues largely depending on the genes affected. A person with this condition has cognitive delay and general motor delay as a result of hypotonia. The child or person has distinct facial features, inability to display expressive speech, and immature sexual organs particularly in males. There are also complex patterns of secondary features observed in patients. For example, a person may have:

• Heart defects
• Severe respiratory infections
• Renal defects
• Epilepsy
• GERD
• Febrile seizures
• Extreme aggression, especially in males
• Autistic like behaviors
• Catatonic like features at start of puberty

The patients also have physical characteristics with both sexes being affected equally. At birth, the weight is perceived to be normal and sometimes it may be above the normal range. In childhood, there is a notable increase in weight that leads to obesity. The individuals may have facial appearances that manifest in form of a broad forehead, small head circumstance, eye lids that slightly slant upward, un-brow or synophrys, and mid-facial hypoplasia that presents with jaw and cheekbones not developing as quickly as other areas of the face. A child may have short nose that has an upturning tip, thickened ear helices, protruding tongue, and upper lip that has cupid bow. If a patient has most of these features, a doctor is likely to suggest genetic testing because they present in a number of genetic deformities or defects. Geneticists need to gain more education on these characteristics to help them diagnose Kleefstra syndrome at birth rather than having years of testing done for other syndromes.

Children with the condition may have behavioral characteristics that present in the following ways:

• They are mellow, passive, sociable, outgoing, and caring
• They tend to relate better to adults compared to their peers
• Have little or no anxiety to strangers
• They prefer observing than playing with peers

Among the problem behaviors children with Kleefstra syndrome display include:

• Having difficulties with tolerating high pain
• Aggression in form of hitting, biting, and pulling hair
• Unpredictable mood swings
• Easily frightened
• Dislike of changes in their routine tasks
• Feeling insecure

Diagnosis

 Diagnosis of Kleefstra syndrome is done through a genetic testing referred to as Fluorescence in-situ hybridization or FISH. It is a relatively new method of testing for the disorder and its lack of availability in various areas may contribute to the low rate of diagnosis. Until April 2010, the disorder was referred to as 9q34.3 deletion syndrome. The name was associated with the missing gene within the chromosome 9. However, the name changed to Kleefstra Syndrome after a clinical geneticists and researcher discovered a pattern in symptoms among children with 9q deletion. The researcher, Dr. Tjitske Kleefstra is from Radboud University’s Nijmegen Medical Centre in Netherlands.

Many kids have lived for many years having diagnoses for other syndromes like Atypical Rhett’s Syndrome, Angelman’s Syndrome, and Fragile X until they were recently diagnosed of Kleefstra Syndrome.

Treatment of Kleefstray Syndrome

In treating Kleefstra syndrome, early intervention is very important. A child who is diagnosed of the condition requires early referral to early childhood intervention programs that are appropriate of his or her age. There are also special education programs that may help the child. Vocational training helps the child to attain her full potential in leading life or engaging in work.

Expressive speech may not be present or it may be severely delayed, however, other kinds of communication can be heightened. Sign language may help the child in communication. The child may need a Picture Exchange Communication System (PECS) to help with communication.

It has been observed that many of the children with the disorder have hypotonia or low muscle tone and physical therapy may help provide support if there are delays in gross motor. A therapist can help the child to develop his or her gross motor skills like crawling, rolling, climbing stairs, and walking.  By the time a child with Kleefstray syndrome enters school, he or she will be walking.  However, because of the low muscle tone, it makes them to be unable to walk for long distance or they tend to get tired quickly. They may also not be able to stand for a long duration. Physical therapy can help improve these physical challenges.

A child may need occupational therapy to help build fine motor skills and acquire self help skills that are essential in their day-to-day life experiences. Also, speech therapy combined with occupational therapy can help with problems like feeding, swallowing, and GERD. To help alleviate unusual behaviors and help a child integrate with his or her environment, sensory integration therapy has played a huge role.

Because there may be some visual impairment in a child with Kleefstra syndrome, he or she may require vision therapy. The brain of the child may not accurately process what the eyes see resulting in cortical visual impairment though the eyes may be structurally typical. You may find that the child is near sighted, and has a squint or strabismus.

Specialized care is needed for children with extreme behavior problems, sleep disorders, movement disorders, and epilepsy. Puberty hormones can help with mood swings and difficulty behaviors. Psychiatric care is helpful in teenage years though it has shown some recovery in adults.

In people who have frequently night awakenings, melatonin may help reduce the episodes. Other problems like renal, cardiac, and hearing loss require standard treatment. Ongoing monitoring is important to see how the child progresses with the various forms of treatment and therapies. Often, repetitive teaching seems to be the only way to help a child with the disorder to learn new tasks.

In essence, many children with Kleefstra syndrome have epilepsy, a third of them actually. You also want to be aware of the soft stool that indicates constipation. The problem is that you may not be able to tough and feel the softness of the stool, so abdominal X-rays (AXRs) may help detect constipation. Sometimes, caecostomies and colectomies may be needed to manage constipation.  Delayed gastric empting may result in reflux or vomiting and in such cases, erythromycin medication may be prescribed to increased gastric motility.

Children with this disorder typically understand more than they communicate, so you want to know what’s normal for them. During or after puberty, there may be sleep disturbances that last for more than 48 hours something that may signify psychosis or the start of regression. Anti-psychotics may be prescribed but doctors and parents should be aware of paradoxical response to benzodiazepines, they can result in drug dependency hence addiction.

Kleefstra Syndrome – Life Expectancy

It is not known how long people with Kleefstra syndrome may survive because the condition is a recent diagnosis. Looking at someone who has severe intellectual disability, they could live up to 55. If a person has other health problems, or if the symptoms are serious such as heart and renal related problems, it makes them to be at more risk, or not being able to live for longer. Having underlying health problems such as heart disease affects the survival of the patient depending on the ability of doctors to correct the heart defect. Because children can be prone to severe infection, it can affect their life expectancy. The susceptibility to infections is due to weaker muscle tone and problems in breathing meaning a child cannot cough up secretions. That’s why pneumonia is common among children who have Kleefstra syndrome.

While Kleefstra syndrome may not necessarily impact on the life expectancy of an individual, the overall life expectancy among people with severe learning disabilities may go down to 55 and it will depend on the situation or complexities of health problems and symptoms in an individual. Usually, early diagnosis is essential to help come up with appropriate treatment regimes and prevent complications.