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 caused by terminal microdeletion of chromosome 9q34 involving loss of the EHMT1 gene, or by mutations that disable the function of the EHMT1 gene. Kleefstra syndrome involves many parts of the body including the brain, muscles, and bones.

Diagnostic testing: The diagnosis of Kleefstra syndrome is made by:

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  Physical examination;

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  Imaging studies of structural brain defects (e.g. microcephaly and brachycephaly); and

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  Is confirmed by the finding of abnormal EHMT1 sequencing.

Physical findings: Children with Kleefstra syndrome have recognizable facial stigmata. Other findings can include:

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  Developmental delay and intellectual disability;

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  Severely limited or absent speech;

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  Hypotonia (weak muscle tone);

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  Eyebrows that grow together in the middle (synophrys);

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  Widely spaced eyes (hypertelorism);

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  Sunken appearance of the middle of the face (midface hypoplasia);

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  Nostrils that open to the front rather than downward (anteverted nares);

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  Protruding jaw (prognathism);

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  Eolled out (everted) lips;

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  Large tongue (macroglossia);

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  Unusually wide and shortened (brachycephaly) or very small (microcephaly) skull;

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  Cardiac defects;

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  Urogenital/renal abnormalities;

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  Seizures; and

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  Tendency to develop severe respiratory infections.

ICD-9: 758.33

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 MER for Evaluation:

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  Clinical history and examination that describes the diagnostic features of the impairment;

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  Genetic testing for microdeletions at chromosome 9q34.3 or pathogenic mutations in the EHMT1 gene; and

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  Developmental assessment or psychological testing to address allegations of mental impairments may be warranted.

REMARKS

Listing-level severity must be documented; and evaluated under the most affected body systems.