Case Report: Blepharophimosis and Ptosis as Leading Dysmorphic Features of Rare Congenital Malformation Syndrome With Developmental Delay - New Cases With TRAF7 Variants

Abstract

Germline variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) gene have recently been described in about 50 patients with developmental delay and cardiac, facial, and digital anomalies (CAFDADD). We aimed to depict further the clinical and genetic spectrum associated with TRAF7 germline variants in two additional patients, broaden the mutational spectrum, and support the characteristic clinical variety to facilitate the diagnostics of the syndrome among physician involved in the evaluation of patients with developmental delay/congenital malformations.

Keywords: TRAF7 variants; blepharophimosis; developmental delay; dysmorphic features; facial features; ptosis.

Figure 1

The facial phenotype of Case 1 at 11 months. Note the significant short palpebral fissures, ptosis, epicanthic folds and high forehead with flat, broad nasal bridge.

Figure 2

The facial phenotype of Case 2 and 16 months. Not the high and broad forehead, flat nasal bridge, short palpebral fissures and ptosis, thin lips.

Figure 3

Amplicon deep sequencing validation of TRAF7 gene variants identified by WES in (A) Case 1, de novo p.(His570Asp), (B) Case 2, de novo p.(Leu595Val). Integrative Genomic Viewer screenshots are presented.