(MIM 610253)

(Kleefstra syndrome)

Prevalence: < 1/106. Autosomal dominant transmission, or, more often de novo mutation. Cytogenetic affection characterized by a microdeletion (subtelomeric deletion) (9q.34.3) (85 %) or by a specific mutation of the euchromatic histone-lysine N-methyltransferase 1 gene (EHMT1) (rarely) .

The importance of malformations depends in part on the number of genes included in the deletion; the described minimum deletion includes at least 14 genes (including EHMT1 and CACNA1B).

The common phenotype includes a:

• mental retardation with hypotonia, often associated with structural abnormalities of the brain
• lack of development of speech
• characteristic facial dysmorphism that includes microcephaly with brachycephaly, hypertelorism, synophrys, midface hypoplasia with protrusion of the tongue (sometimes leading to confusion with trisomy 21 in the neonatal period), eversion of the lower lip  and prognathism.

Birth weight is often increased and there is a risk of obesity in childhood. Delayed motor development. Behavioral disorders are common: apathy, bipolar disorder, regression, aggression (adolescence) or autistic traits.

A cardiac defect is sometimes associated: ASD, VSD, tetralogy of Fallot, coarctation of the aorta,  aortic bicuspidism. An atrial flutter has been observed in some patients. Epilepsy is common  (30 %). Hypotonia with catatonia can be observed in adolescence.

Occasionally: tracheobronchomalacia, gastroesophageal reflux, episodes of upper airway obstruction, genitourinary anomalies (hypospadias, micropenis, hydronephrosis, vesicoureteral reflux with possible renal failure).

Anesthetic implications:

preoperative echocardiography, check renal function, risk of upper airway obstruction or difficult intubation, epilepsy,  mental retardation

References : 

-        Willemsen MH, Vulto-van Silfhout AT, Nillensen WM, Wissink-Lindhut WM et al.
Update on Kleefstra syndrome.
Molecular Syndromology 2011; 2: 202-12.

-        Anaesthesia recommendations for Kleefstra syndrome:  www.orphananesthesia.eu

Updated: December 2020