Information

Kleefstra syndrome* (KS) is a rare genetic condition in humans caused by a deletion or mutation of the gene known as EHMT1. The deletion or mutation of the gene occurs in one of the two copies of a person’s chromosome 9. The EHMT1 deletion or mutation is almost always “de novo”, meaning that it is something that neither parent possessed or transmitted (although this may be possible in certain rare cases). The EHMT1 gene codes specifically for the production of a protein called euchromatin histone methyltransferase 1. A patient with KS is said to be haploinsufficient, meaning that the remaining level of EHMT1 protein activity is insufficient because one gene copy is not functional. EHMT1 is a critical gene in human development and function. The protein that is to be produced is part of the “epigenetic machinery” and is believed to be involved in the important process of silencing (or turning “off”) other genes; therefore, its deficiency results in a number of often serious medical issues discussed below.

KS is characterized by intellectual disability and various other neurological and physical abnormalities. *With respect to intellectual disability, the majority of individuals are believed to function in the moderate to severe spectrum with an IQ of less than 70 in many cases.

*Most patients have severe expressive speech delay with little speech development, although nonverbal communication may be possible.

*With respect to other neurological and physical abnormalities, a patient may have childhood hypotonia (low muscle tone which is often associated with reduced muscle strength, and therefore, reduced basic gross motor skills such as walking),

*distinctive facial features (including mid-face hypoplasia, short nose/depressed nasal bridge, thin upper lip and open mouth in infancy with protruding tongue),

*various developmental delays and other physical abnormalities.

Other physical abnormalities include heart defects, renal/urologic defects, genital defects in males, severe respiratory infections and epilepsy/febrile seizures.

 Behavioural abnormalities may include extreme apathy or catatonic-like features during or after puberty and autistic-like features in childhood (KS patients are often dual diagnosed with Autism Spectrum Disorder). 

In certain more severe cases, death has resulted from abnormalities or complications caused by KS. Included in this section is a comprehensive list of known features of KS patients, although it is important to note that the patient population remains small (which may lead to conclusions changing over time) and situations can vary from patient-to-patient.

Currently, there is no drug or similar therapeutic treatment for KS patients. As a result, managing KS on a day-to-day basis involves various therapies (mostly commonly speech, physical, occupational and behavioral), assistance of a parent or caregiver, careful monitoring of symptoms and making lifestyle choices based on the patient’s needs. Well-known medications may also be used to treat specific features such as epilepsy or behavioral problems.

According to K.I.D.S. IQ Project’s records currently indicate that the worldwide KS population is approximately 500 people.  It was recently founded in 2010 by Dr. Kleefstra.

Common or Core Features

• Intellectual disability (IQ of 70 or less)
• Limited or no speech capabilities
• Various developmental delays
• Low muscle tone, hypotonia
• Autistic-like features

Other Possible Features

• Facial appearance may be similar to other KS patients
• Heart conditions
• Seizures
• Genital anomalies in males
• Sleep difficulties
• Behavioral difficulties
• Strabismus (squint) or other unusual eye features
• Respiratory infections caused by aspiration reflux/GERD.
• Microcephaly
• Slightly unusual hands and/or feet (single palm crease, incurving fingers, short or tapering fingers, unusually positioned feet)
• Hearing impairment
• Kidney anomalies
• Connective tissue disorders, including lax joints and hernias.
• Patches of lighter skin coloring
• Dental anomalies
• Anal atresia (the normal opening for the anus is not present)
• Possibly overweight

Management and Treatment

There is no current cure or specific treatment for Kleefstra.

A Treatment plan requires a multidisciplinary team, specializing in patients with intellectual deficiencies. Special education and vocational training along with speech therapy, physical therapy, behavioral therapy, occupational therapy and sensory integration therapy are recommended from an early age. Standard treatment is necessary for those with renal, cardiac and urologic issues and for hearing loss. Psychiatric care along with behavioral intervention therapy may be needed. Cardiac screening (for the presence of arrhythmias) as well as intestinal and renal/urologic monitoring is recommended. Medical follow-up is life-long.