Expanding the phenotype and genotype in Thauvin-Robinet-Faivre syndrome: A new patient with a novel variant and additional clinical findings

DÜZENLİ T., Sezer A., KAYHAN G., ARSLAN A., Percin F. E.

American Journal of Medical Genetics, Part A, cilt.191, sa.8, ss.2232-2239, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 191 Sayı: 8
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1002/ajmg.a.63300
  • Dergi Adı: American Journal of Medical Genetics, Part A
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source, BIOSIS, CAB Abstracts, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.2232-2239
  • Anahtar Kelimeler: CLCN4, FIBP, overgrowth, recurrent pulmonary infections, Thauvin-Robinet-Faivre syndrome, TLR5
  • Gazi Üniversitesi Adresli: Evet

Özet

Thauvin-Robinet-Faivre syndrome (TROFAS; OMIM #617107) is a rare autosomal recessive overgrowth syndrome characterized by generalized overgrowth, dysmorphic facial features, and delayed psychomotor development caused by biallelic pathogenic variants in the FGF-1 intracellular binding protein (FIBP) gene. To date, only four patients from two families have been reported. In this report, we present a 4-year-old male patient with generalized overgrowth and delayed developmental milestones consistent with this syndrome. In addition, he has unique features that were not reported in previous patients, including drooling, recurrent pulmonary infections, chronic pulmonary disease, hyperextensible elbow joints, hypoplastic nipples, unilateral cryptorchidism, and frequent spontaneous erections. We identified a homozygous, likely pathogenic variant, c.415_416insCAGTTTG (p.Asp139AlafsTer3), which causes a frameshift in the FIBP. Additionally, we identified a homozygous missense variant in the Toll-like receptor 5(TLR5) gene and a hemizygous missense variant in the chloride voltage-gated channel 4 (CLCN4) gene, with uncertain significance in either case. In this article, we set out the new observations and also discuss the frequency of the characteristic findings of the syndrome in the patients so far reported.