A Unique Observation of a Patient with Vulto-van Silfhout-de Vries Syndrome

Abstract

Introduction: Vulto-van Silfhout-de Vries Syndrome (VSVS; OMIM#615828) is a rare hereditary disease associated with impaired intellectual development and speech, delayed psychomotor development, and behavioral anomalies, including autistic behavioral traits and poor eye contact. To date, 27 patients with VSVS have been reported in the literature. Materials and Methods: We describe a 23-year-old male patient with autism spectrum disorder (ASD) who was admitted to the gastroenterological hospital with signs of pseudomembranous colitis. ASD was first noted in the patient at the age of 2.5 years. Later, he developed epileptic seizures and important growth retardation. Prior to the hospitalization, chromosomal aberrations, Fragile X syndrome, and aminoacidopathies/aminoacidurias associated with ASD were excluded. Whole-genome sequencing (WGS) was prescribed to the patient at 23 years old. Results: The patient had a heterozygous carrier of “de novo” variant c.662C > T (p.S221L) in exon 4 of the DEAF1 gene. c.662C > T had not been previously described in genomic databases. According to the ACMG criteria, this missense variant was considered to be pathogenic. VSVS was diagnosed in the patient. Conclusions: The phenotype of the patient is very similar to the data presented in the world literature. However, growth retardation and cachexia, which have not been described previously in the articles, are of interest.

Keywords: DEAF1; VSVS; VULTO-VAN syndrome.

Figure 1

The structure of the DEAF1 gene and the spectrum of gene variants detected earlier in patients with VSVS. * Termination of protein synthesis.

Figure 2

Phenotype of the patient with Vulto-Van Silfhout-De Vries Syndrome at different ages. (A) Patient at 5 months of age; (B) patient at 10 months of age; (C) patient at 4 years old; (D) patient at 6 years old, (E) patient at 23 years old, (F) dermatoglyphics of the palms of the patient at 23 years old.

Figure 3

Pedigree of the patient with Vulto-Van Silfhout-De Vries Syndrome.

Figure 4

Electrophoregram of the nucleotide sequence of the DEAF1 gene. (A) Substitution c.662C > T in the heterozygous state in the proband (indicated by the arrow). (B) The wild-type genotype at position c.662 in the sister, mother, and father of the proband (indicated by the arrow).