2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Heterozygous <em>ACTB</em> Pathogenic Variant Causing Baraitser-Winter Syndrome Presenting With Tracheal Ring, Intestinal Atresia, and Neonatal Diabetes

Pdf Summary

This case report describes the presentation of a 6-week-old male with a rare genetic disorder called Baraitser-Winter cerebrofrontofacial syndrome (BWCFFS) caused by a heterozygous pathogenic variant in the ACTB gene. The patient was conceived via in vitro fertilization and had respiratory distress at birth due to a tracheal ring, which required a cricoidectomy for intubation. Genetics was consulted due to anomalies, extensive prenatal history, and persistent hyperglycemia despite high insulin doses. The patient also had leukopenia, anemia, and low pancreatic elastase levels. There was no pertinent family history. The physical exam revealed characteristic features of BWCFFS, including intellectual disability, pachygyria, microcephaly, shoulder girdle muscle wasting, and visual and/or auditory impairments.<br /><br />This case adds to the existing literature on a distinct presentation associated with a specific genotype in BWCFFS. The key findings of this new phenotype include hyperglycemia, intestinal atresia, edema, and laryngeal anomalies. Three previously published cases with the same ACTB variant were described, one with jejunal atresia and hyperglycemia, and another with small bowel atresia, laryngeal dysgenesis, and persistent hyperglycemia. The patient in this case had similar features of hyperglycemia and intestinal atresia.<br /><br />Further investigations through genetic testing confirmed the presence of the ACTB c.1043C>T (p.S348L) variant, supporting the diagnosis of BWCFFS. The patient's clinical features were consistent with the genotype-phenotype correlation observed in previous cases with the same variant. The patient exhibited dysmorphic facial features, low-set ears, exophthalmos, down-slanting palpebral fissures, hypoplastic nipples, and generalized hypotonia. Surgical examination revealed an apple-peel gross appearance of intestinal atresia.<br /><br />Overall, this case highlights the importance of considering ACTB in monogenic or congenital diabetes gene panels. The identification of this pathogenic variant provides valuable information for understanding the genetic basis of BWCFFS and its associated clinical features.

Asset Subtitle

Co-Author - Jeremy Hill, DO; Presenting Author - Kathleen Shields, MS; Co-Author - David Rodriguez-Buritica, MD; Co-Author - Laura S. Farach, MD; Co-Author - Paul R. Hillman, MD/PhD;

Meta Tag

Congenital Anomaly

Diabetes

Dysmorphology

Gastrointestinal System

Genetic Testing

Genome sequencing

Genotype-Phenotype Correlations

Phenotype

Co-Author Jeremy Hill, DO

Co-Author David Rodriguez-Buritica, MD

Co-Author Laura S. Farach, MD

Co-Author Paul R. Hillman, MD/PhD

Presenting Author Kathleen Shields, MS

Keywords

Baraitser-Winter cerebrofrontofacial syndrome

BWCFFS

genetic disorder

ACTB gene

respiratory distress

tracheal ring

cricoidectomy

hyperglycemia

leukopenia

anemia