How many phenotypes for the FBXO11 related disease? Report on a new patient with a tricho-rhino-phalangeal like phenotype

Abstract

Here we report the case of a young boy with developmental delay, thin sparse hair, early closure of the anterior fontanel, bilateral choanal atresia, brachyturicephaly; and dysmorphic features closely resembling those seen in trichorhinophalangeal syndrome (TRPS). These features include sparse hair, sparse lateral eyebrows, a bulbous pear shaped nose, a long philtrum, thin lips, small/hypoplastic nails, pes planovalgus; bilateral cone-shaped epiphyses at the proximal 5th phalanx, slender long bones, coxa valga, mild scoliosis, and delayed bone age. Given that TRPS had been excluded by a thorough genetic analysis, whole exome sequencing was performed and a heterozygous likely pathogenic variant was identified in the FBXO11 gene (NM_001190274.2: c.1781A > G; p. His594Arg), confirming the diagnosis of the newly individualized IDDFBA syndrome: Intellectual Developmental Disorder, dysmorphic Facies, and Behavioral Abnormalities (OMIM# 618,089). Our findings further delineate the clinical spectrum linked to FBXO11 and highlight the importance of investigating further cases with mutations in this gene to establish a potential genotype-phenotype correlation.

Keywords: Dysmorphology; Intellectual disability; Microcephaly; Scoliosis; Whole exome sequencing.