What is Kleefstra Syndrome?

Kleefstra syndrome (KS) is a rare genetic disorder characterized by intellectual disability, childhood hypotonia, severe expressive speech delay and a distinctive facial appearance with a spectrum of additional clinical features. The syndrome, eponymously named for Dr. Tjitske Kleefstra, is caused by either a mutation or deletion of a gene called EHMT1 (Euchromatic Histone Methyltransferase 1). The impact leads to the loss of the entire gene.
Kleefstra Syndrome presents with a wide range of symptoms, and the severity of those symptoms vary from mild to severe.

The symptoms & features of Kleefstra Syndrome may include:

Physical Features

  • ​Hypotonia (Low muscle tone)
  • Unusually small head (microcephaly)
  • A wide, short skull (brachycephaly)
  • Distinctive facial features which could include eyebrows that grow together in the middle, sunken appearance in the middle of the face, widely spaced eyes, nostrils that open to the front rather than downward, a protruding jaw, rolled out lips, and a large tongue
  • High birth weight and weight control issues as children/adult
  • Unusual hands/feet (position, shape, or size)
  • Dental abnormalities
  • Skin that may be discolored or lighter in areas
  • Anal atresia

Neurological Features

  • Intellectual disabilities
  • Limited or absent speech capabilities
  • Various global developmental delays
  • Autistic-like features and characteristics
  • Seizures
  • Sleep disorders
  • Behavioral difficulties
  • Visual impairments
  • Difficulty swallowing
  • Impairments in hearing (may have several inconclusive hearing test results)
  • General loss of interest and enthusiasm as they get older
  • General Regressive behavior as they get older of interest and enthusiasm as they get older

Clinical Features

  • Structural brain abnormalities
  • Congenital heart defects
  • Abnormalities of the genitalia
  • Tendency to develop severe respiratory infections
  • Kidney abnormalities

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Testing and Diagnosis

Diagnostic testing for Kleefstra Syndrome or any other rare genetic syndrome that may be linked to an intellectual disability can be done by:

  • Exome Sequencing
  • Whole Genome Sequencing
  • Microarray Analysis
  • FISH Analysis
  • Methylation Signature (EpiSign) Testing

Disorders to consider in the differential diagnosis of Kleefstra Syndrome are:

  • Downs Syndrome
  • Smith-Magenis Syndrome
  • Pitt-Hopkins Syndrome
  • Angelman Syndrome
  • KMT2C-associated syndrome
  • MBD5 haploinsufficiency

Indicators of Kleefstra Syndrome:

  • Low muscle tone
  • Developmental delays or intellectual disabilities
  • Unusual physical features
  • Seizures or abnormal EEG
  • Movement disorders or motor delay
  • Autism spectrum disorder
  • Psychiatric or behavioral disorders
  • Nonspecific brain abnormalities

Therapies and Early Interventions

Therapy intervention at an early age has been proven to be one of the most effective ways to improve the quality of life for individuals with Kleefstra Syndrome. The early intervention team may consist of therapists and medical specialists trained to help develop skills such as:

  • Cognitive skills (thinking, learning, problem-solving)
  • Communication skills (gesturing, talking, listening, understanding)
  • Physical and sensory skills (crawling, walking, climbing, seeing, hearing)
  • Social-emotional skills (playing, understanding feelings, making friends)
  • Adaptive or self-help skills (eating, bathing, dressing)

Therapies and Early Interventions

Therapy intervention at an early age has been proven to be one of the most effective ways to improve the quality of life for individuals with Kleefstra Syndrome. The early intervention team may consist of therapists and medical specialists trained to help develop skills such as:

  • Cognitive skills (thinking, learning, problem-solving)
  • Communication skills (gesturing, talking, listening, understanding)
  • Physical and sensory skills (crawling, walking, climbing, seeing, hearing)
  • Social-emotional skills (playing, understanding feelings, making friends)
  • Adaptive or self-help skills (eating, bathing, dressing)

Many of the more common therapies, medical and behavioral interventions are listed below.

Therapy Interventions:

  • Speech Therapy
  • Occupational Therapy
  • Physical Therapy
  • Social/Group Therapy
  • ABA Therapy

The below therapies have been recommended by many families, and have shown some degree of success, although there is not a wealth of research to confirm this currently.

  • Hippotherapy (horseback riding)
  • Music Therapy
  • Hydrotherapy (water exercises)

Behavioral Interventions:​

Individuals with Kleefstra Syndrome have can often times be extremely friendly and have a happy disposition based on what many family members and caregivers have reported. At times, they can be overly friendly and ignore typical social boundaries. In addition to this, individuals may experience other behavioral issues such as obsessive-compulsive disorders, aggression towards self or others, anxiety, change resistant with regards to routine, mood swings, and insecurities. Many families have observed an uptick in the problematic behaviors as a child enters puberty. At times, it is necessary to consult a medical professional if behavior issues increase or cause harm. It is advised to make sure the individual is not experiencing a medical/health ailment or lack of sleep before medicating for behaviors.

Medical Interventions:

Individuals with Kleefstra Syndrome can have complex medical conditions that should be monitored by specialists regularly. These are listed on the symptoms page. ​In addition, individuals may experience sleep pattern disturbances, gastrointestinal conditions, and epilepsy. At times, medication may be prescribed, but should be done so at the hands of a medical professional after close examination and observation. Medication is especially important if an individual is experiencing sleep disturbances causing them to be awake for a period of time longer than 48 hours.

It has also been reported by many families and care givers that special diets can help improve medical and behavior patterns in individuals with Kleefstra Syndrome as they can often times suffer from gastrointestinal conditions.

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