Variable developmental delays and characteristic facial features—A novel 7p22.3p22.2 microdeletion syndrome?

Abstract

Isolated 7p22.3p22.2 deletions are rarely described with only two reports in the literature. Most other reported cases either involve a much larger region of the 7p arm or have an additional copy number variation. Here, we report five patients with overlapping microdeletions at 7p22.3p22.2. The patients presented with variable developmental delays, exhibiting relative weaknesses in expressive language skills and relative strengths in gross, and fine motor skills. The most consistent facial features seen in these patients included a broad nasal root, a prominent forehead a prominent glabella and arched eyebrows. Additional variable features amongst the patients included microcephaly, metopic ridging or craniosynostosis, cleft palate, cardiac defects, and mild hypotonia. Although the patients' deletions varied in size, there was a 0.47 Mb region of overlap which contained 7 OMIM genes: EIP3B, CHST12, LFNG, BRAT1, TTYH3, AMZ1, and GNA12. We propose that monosomy of this region represents a novel microdeletion syndrome. We recommend that individuals with 7p22.3p22.2 deletions should receive a developmental assessment and a thorough cardiac exam, with consideration of an echocardiogram, as part of their initial evaluation.

Deletion of chr7p22 and chr15q11: Two Familial Cases of Immune Deficiency: Extending the Phenotype Toward Dysimmunity

“…LFNG, like PDGFalpha, seems a priori well tolerated (pLI = 0.42). This was in agreement with the study of Yu et al (7). There, they discussed the implication of this gene in the phenotype of their patients, and concluded that haploinsufficiency of only LFNG could not be the cause of the phenotype of these 5 patients.…”

“…The deleted 7p22 region spans 58 genes, including some that could be linked with the clinical signs of patient 1. There is also a large sequence overlap with patients 4 and 5 of Yu and colleagues' case report (7), which is similarly dysmorphic, with no reported hematologic manifestations. In this study, the patients displayed weaknesses in language skills, as well as in motor skills.…”

Clinico-pathological correlation in case of BRAT1 mutation

“…Mundy described decreased myelination in such cases [17]. Yu described unspecific hypomyelination in a 3-year-old child [38]. Ommeron described delayed myelination at a few weeks of age [19].…”

Partial trisomy 16q and partial monosomy 7p of a fetus derivated from paternal balanced translocation

“…Andrea C. Yu reported 5 patients with microdeletions at 7p22.3p22.2. [ 44 ] The most facial features in these patients include a broad nasal root, a prominent forehead a prominent glabella and arched eyebrows, micrognathia, metopic ridging or craniosynostosis, cleft palate, cardiac defects, and mild hypotonia. Micrognathia is also present, but no gene is found to be associated with this phenotype in this region.…”