[MIM 617 140]

(acronym for Zhu-Tokita-Takenouchi-Kim)

Very rare: < 1/106. De novo mutation or autosomal dominant transmission of a loss of function mutation of the SON gene (21q22.1) coding for the SON protein that binds to DNA and RNA, and plays an important role in mRNA transcription and splicing. Mitochondrial metabolism and protein O-glycosylation are affected by this mutation.

Multisystemic pathology that combines in a variable way:

-        developmental delay: small size (50 %)

-        more or less severe intellectual deficit (100 %)

-        hypotonia

-        facial dysmorphism: asymmetry of the face, low-set ears, wide base of the nose, short or smooth philtrum, frontal bumps, retraction of the  midface

-        cerebral abnormalities (80 %): macrocephaly, ventriculomegaly, white matter abnormalities, polymicrogyria, hypoplasia of the corpus callosum and cerebellar hemispheres, Chiari type1 malformation, delayed speech, convulsions (60 %) that appear between 1 and 6 years of age

-        ocular abnormalities: sunken eyes, downslanting palpebral fissures downwards, horizontal eyebrows; sometimes optic nerve atrophy, nystagmus, strabismus

-        musculoskeletal abnormalities (80 %): hemivertebrae, scoliosis, kyphosis, small hands and feet, ligament hyperlaxity

-        heart defects: VSD, ductus arteriosus

-        low levels of immunoglobulines: risk of infections

-        sometimes cleft palate (or high arched palate), agenesis of one lung, renal dysplasia

Anesthetic implications:

developmental delay, epilepsy, echocardiography, risk of difficult mask ventilation and intubation (facial asymmetry)

References :

-        Kushary ST, Revah-Politi A, Barua S, Ganapathi M, Accogli A et al.
ZTTK syndrome: clinical and molecular findings ogf 15 cases and a review of the literature.
Am J Med Genet 2021; 185A:3740-53.

-        Dingemans AJM, Truijen KMG, Kim JH, Alacam Z, Faivre L et al.
Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON. 
Europ J Hum Genet 2022 ; 30: 271-81.

-        Hudec J, Kosinova M.
Anesthesia of the patient with Zhu-Tokita-Takenouchi-Kim (ZTTK) syndrome: a case report.
Children 2022, 9, 869. doi.org/10.3390/children9060869

-         Pavone P, Saia F, Pappalardo X, Barbagallo M, Prato A, Rizzo R.
Novel malformations: Chiari type 1 and hydrocephalus in Zhu-Tokita-Takenouchi-Kim syndrome and novel SON variants.
Clin Case Rep.2022;10:e06529. doi: 10.1002/ccr3.6529

-        Zhu-Tokita-Takenouchi-Kim syndrome.
Orphanaesthesia.eu

Update January 2023