Titel: Baraitser-Winter-Cerebrofrontofacial Syndrome 2 with early onset severe autistic behavior: A case report
ID: P-ClinG-062
Art: Postertalk
Redezeit: 2 min
Session: Poster Session
ClinG 2

Referent: Theresia Herget (Hamburg/DE)

Abstract - Text


Baraitser-Winter-Cerebrofrontofacial Syndrome Type 2 (BWCFFS2) is a rare autosomal dominant disorder caused by pathogenic variants in the ACTG1 gene. The phenotype is characterised by craniofacial dysmorphism and developmental delay with a variable degree of intellectual disability, possibly accompanied by sensorineural hearing loss, bilateral ptosis, ocular colobomata, seizures and anterior neuronal migration disorder like lissencephaly or pachygyria. 

We describe a five year old boy, second child to non-consanguineous parents from Greece, showing global developmental delay with absent speech, muscular hypotonia and pes valgoplanus, bilateral sensorineural hearing loss with cochlea implantation, mild facial dysmorphism consisting in low anterior hairline, hypertelorism, long and slightly downslanting palpepral fissures, arched eyebrows with medial flarring, discrete bilateral ptosis, slender triangular nose and a diagnosis of early onset autism. The family history was remarkable of muscular hypotonia, developmental delay and autistic features without dysmorphism in the older brother, caused by a de novo pathogenic variant in the TRIO gene. No other affected family member was reported.

Extended metabolic work up in blood and urine gave normal results. Brain MRI at the age of one year was inconspicuous. EEG showed no pathological findings. Genotyping for the familiar TRIO variant could exclude this variant in our patient. Finally, whole exome sequencing was carried out in him, uncovering  a de novo missense variant NM_001614.5: c.547C>T [p.(Arg183Trp)] in ACTG1. This variant has not been reported so far, however, another exchange (c.548G>A [p.(Arg183Trp)]) at the same amino acid position has been described in a patient with non-syndromic hearing loss. 

Pathogenic variants in ACTG1 have been associated with non-syndromic hearing loss as well as with BWCFFS2, for which a broad clinical variability is known, even within families. In addition to the typical features of BWCFFS like craniofacial dysmorphism, hearing loss and developmental delay our patient shows early onset autism but no brain malformation or seizures. So far, autism has not been described as a major feature of BWCFFS2, probably due to missed diagnosis or lack or reporting. Hereby, we propose, severe autistic behaviour with an onset in early childhood could be part of the clinical manifestations of BWCFFS2 and expansion of the known phenotype.