Program Operations Manual System (POMS)
TN 15 (09-17)
DI 23022.207 Kleefstra Syndrome
9q34 Deletion Syndrome; Chromosome 9q34.3 Deletion Syndrome;
9q34.3 Microdeletion Syndrome; 9q Subtelomeric Deletion Syndrome;
9qSTDS; 9q34.3 Terminal Deletion Syndrome
Kleefstra syndrome is a disorder that involves many parts of the body. Characteristic features of Kleefstra syndrome include developmental delay and intellectual disability, severely limited or absent speech, and weak muscle tone (hypotonia). Distinctive facial features include eyebrows that grow together in the middle (synophrys), widely spaced eyes (hypertelorism), a sunken appearance of the middle of the face (midface hypoplasia), nostrils that open to the front rather than downward (anteverted nares), a protruding jaw (prognathism), rolled out (everted) lips, and a large tongue (macroglossia). The skull may be unusually wide and shortened (brachycephaly) or very small in size (microcephaly), and is often associated with structural brain abnormalities. Other features may include congenital heart defects, genitourinary abnormalities, seizures, and a tendency to develop severe respiratory infections.
Kleefstra syndrome is caused by terminal microdeletion of chromosome 9q34 involving loss of the EHMT1 gene, or by mutations that disable the function of the EHMT1 gene.
DIAGNOSTIC TESTING, PHYSICAL FINDINGS, AND ICD-9-CM CODING
Diagnostic testing: The diagnosis of Kleefstra syndrome is made by physical examination, imaging studies of structural brain defects (e.g. microcephaly and brachycephaly), and is confirmed by the finding of abnormal EHMT1 sequencing.
Physical findings: Children with Kleefstra syndrome have recognizable facial stigmata. Other findings can include: hypotonia, cardiac defects, and urogenital/renal abnormalities.
ONSET AND PROGRESSION
Onset is congenital. Children with Kleefstra syndrome may exhibit features of autism or related developmental disorders affecting communication and social interaction. In adolescence, they may develop a general loss of interest and enthusiasm (apathy) or extreme unresponsiveness (catatonia).
Treatment of Kleefstra syndrome is supportive, and requires ongoing routine care by a multidisciplinary team specializing in the care of children or adults with intellectual disability. Referral to age-appropriate early childhood intervention program, special education, or vocational training. Therapies include speech/language therapy, physical and occupational therapy, and sensory integration. Extreme behavior problems may require treatment by a psychiatrist. Neurologic, cardiac, renal, urologic and other medical issues require standard monitoring and treatment. Medical follow-up is life-long.
SUGGESTED PROGRAMMATIC ASSESSMENT*
Suggested MER for evaluation:
Clinical history and examination that describes the diagnostic features of the impairment.
Genetic testing for microdeletions at chromosome 9q34.3 or pathogenic mutations in the EHMT1 gene.
Developmental assessment or psychological testing to address allegations of mental impairments may be warranted.
Suggested Listings for Evaluation:
Listing-level severity must be documented; and evaluated under the most affected body systems.