Baraitser-Winter syndrome (BRWS) is a rare autosomal dominant disease (AD) caused by heterozygous variants in ACTB (BRWS1) or ACTG1 (BRWS2) genes. BRWS features developmental delay/intellectual disability of variable degree and craniofacial dysmorphisms. Brain abnormalities (especially pachygyria), microcephaly, epilepsy, as well as hearing impairment, cardiovascular and genitourinary abnormalities may be present. We report on a 4-year-old female, who was addressed to our institution because of psychomotor delay associated with microcephaly and dysmorphic features, short stature, mild bilateral sensorineural hearing loss, mild cardiac septal hypertrophy, and abdominal swelling. Clinical exome sequencing detected a c.617G>A p.(Arg206Gln) de novo variant in ACTG1 gene. Such variant has been previously reported in association with a form of AD nonsyndromic sensorineural progressive hearing loss and we classified it as likely pathogenic according to ACMG/AMP criteria, despite our patient's phenotype only partially overlapped BWRS2. Our finding supports the extreme variability of the ACTG1-related disorders, ranging from classical BRWS2 to nuanced clinical expressions not fitting the original description, and occasionally featuring previously undescribed clinical findings.

Graziani, L., Cinnirella, G., Ferradini, V., Conte, C., Bascio, F.l., Bengala, M., et al. (2023). A likely pathogenic ACTG1 variant in a child showing partial phenotypic overlap with Baraitser-Winter syndrome. AMERICAN JOURNAL OF MEDICAL GENETICS. PART A, 191(6), 1565-1569 [10.1002/ajmg.a.63157].

A likely pathogenic ACTG1 variant in a child showing partial phenotypic overlap with Baraitser-Winter syndrome

Ferradini, Valentina;Sangiuolo, Federica;Novelli, Giuseppe
2023-06-01

Abstract

Baraitser-Winter syndrome (BRWS) is a rare autosomal dominant disease (AD) caused by heterozygous variants in ACTB (BRWS1) or ACTG1 (BRWS2) genes. BRWS features developmental delay/intellectual disability of variable degree and craniofacial dysmorphisms. Brain abnormalities (especially pachygyria), microcephaly, epilepsy, as well as hearing impairment, cardiovascular and genitourinary abnormalities may be present. We report on a 4-year-old female, who was addressed to our institution because of psychomotor delay associated with microcephaly and dysmorphic features, short stature, mild bilateral sensorineural hearing loss, mild cardiac septal hypertrophy, and abdominal swelling. Clinical exome sequencing detected a c.617G>A p.(Arg206Gln) de novo variant in ACTG1 gene. Such variant has been previously reported in association with a form of AD nonsyndromic sensorineural progressive hearing loss and we classified it as likely pathogenic according to ACMG/AMP criteria, despite our patient's phenotype only partially overlapped BWRS2. Our finding supports the extreme variability of the ACTG1-related disorders, ranging from classical BRWS2 to nuanced clinical expressions not fitting the original description, and occasionally featuring previously undescribed clinical findings.
giu-2023
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MED/03 - GENETICA MEDICA
English
ACTG1
BRWS2
Baraitser-Winter syndrome
clinical exome sequencing
Graziani, L., Cinnirella, G., Ferradini, V., Conte, C., Bascio, F.l., Bengala, M., et al. (2023). A likely pathogenic ACTG1 variant in a child showing partial phenotypic overlap with Baraitser-Winter syndrome. AMERICAN JOURNAL OF MEDICAL GENETICS. PART A, 191(6), 1565-1569 [10.1002/ajmg.a.63157].
Graziani, L; Cinnirella, G; Ferradini, V; Conte, C; Bascio, Fl; Bengala, M; Sangiuolo, F; Novelli, G
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/321981
Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 0
  • ???jsp.display-item.citation.isi??? 0
social impact