Dados do Trabalho

Título

Kleefstra syndrome: differential diagnosis of motor delay in syndromic autism

Apresentação dos casos

Pre-schooler, 3 years old, history of dizygotic twinning and prematurity (gestational age 33s), presence of facial dysmorphisms (synophrys, wide and arched eyebrows, palpebral fissures inclined downwards, ocular hypertelorism, flat nasal base, maxillary hypotonia), as well as onset and developmental motor delay, central pattern hypotonia, sleep disturbance and, in parallel, a diagnosis of ASD (Autism Spectrum Disorder) support level 2 with significant impairment in verbal communication.
Son of a mother with Myotonic Dystrophy type 1 (seventh case in the family), whose only pregnancy was through in vitro fertilization, and twin brother also with classic ASD. Initially admitted to the neuromuscular outpatient clinic at our service, he underwent
exome analysis showed a pathogenic mutation in the KMT2C- NM_170606.3(KTMC):c.11598_11601del;p.(lys3867Glyfs*21) gene.

Discussão

Although motor delay and hypotonia are described in classic ASD as secondary to sensory impairment, they do not assume relevant levels of severity. In the case described, the motor delay was early, with a starting pattern and delay in evolutionary milestones,
This, together with central hypotonia and the presence of dysmorphisms, was decisive in characterizing the individual's ASD as syndromic. Molecular analysis led to the specific diagnosis of Kleefstra Syndrome, the description of which includes autism,
dimorphisms compatible with those presented in the case, significant sleep disturbance, motor delay and verbal language impairment, which requires therapeutic individualization, including encouraging alternative communication.

Comentários finais

The importance of genetic investigation in patients with motor impairment in syndromic ASD stands out. In the case described, despite the relevant family history of myotonic dystrophy, the hypotonia pattern was decisive for the etiological diagnosis. The specific diagnosis allows therapeutic individualization and better clinical management.

Referências

1. Koemans, Tom S et al. “Functional convergence of histone methyltransferases EHMT1 and KMT2C involved in intellectual disability and autism spectrum disorder.”
PLoS genetics vol. 13,10 e1006864. 25 Oct. 2017, doi:10.1371/journal.pgen.1006864
2. Faundes, V., Newman, W. G., Bernardini, L., Canham, N., Clayton-Smith, J., Dallapiccola, B., Davies, S. J., Demos, M. K., Goldman, A., Gill, H., Horton, R., Kerr, B., and 11 others. Histone lysine methylases and demethylases in the landscape of human developmental disorders. Am. J. Hum. Genet. 102: 175-187, 2018

Palavras Chave

Kleefstra Syndrome; Genetic Research; AUTISM SPECTRUM DISORDER