Ophthalmic and Systemic Findings in Interstitial Deletions of Chromosome 14q: A Case Feport and Literature Review

Abstract

We report a patient with clinical anophthalmia, partial eyelid fusion and a hypoplastic socket on the right. The left eye has microphthalmia involving the anterior and posterior segments, microcornea, iris coloboma, chorioretinal dysgenesis, macular dysplasia, absence of retinal vessels, and optic nerve aplasia. Systemic abnormalities include microcephaly, bilateral hearing loss, and duodenal atresia. Electrophysiologic testing showed no response from either eye. Cytogenetic testing revealed a de novo interstitial deletion of chromosome 14q22.3q23.1. The literature of similar interstitial deletions and ongoing candidate gene studies are reviewed.

Haploinsufficiency of BMP4 gene may be the underlying cause of Frías syndrome

“…In 1991, Bennett et al was the first to suggest a relationship between the 14q22–q23 deletion and the presence of anophthalmia/microphthalmia (A/M) and pituitary malformations. This observation was followed by at least nine more reports of patients with A/M and other eye defects, and deletions of the 14q22–q23 region [Elliott et al, ; Lemyre et al, ; Nolen et al, ; Thienpont et al, ; Bakrania et al, ; Hayashi et al, ; Reis et al, ; Lumaka et al, ; Pearce et al, ]. These included an article that described four family members with the same deletion of 14q22.1–q22.2 and highly variable manifestations [Lumaka et al, ]; therefore, we present the second reported family carrying the same chromosomal deletion, and the first with a clinical diagnosis of a syndrome [Frías et al, ; Martínez‐Frías et al, ].…”

Anophthalmia, hearing loss, abnormal pituitary development and response to growth hormone therapy in three children with microdeletions of 14q22q23

“…Anophthalmia and other ocular anomalies were associated with heterozygous defects in OTX2 [3,8,9] or BMP4 [7,10,11], and also with deletions involving both these genes [4,6,12]. While OTX2 was deleted in all our patients, BMP4 was deleted only in Patient 1 (Figure 2).…”

“…Nevertheless, the ocular phenotype was similar in all three children. The phenotypic effect of OTX2 and BMP4 disruptions is very variable ranging between anophthalmia/microphthalmia, corneal opacity and no abnormality at all, even in family members with the same mutation [2,5,9-13], and the phenotype does not have to be more severe in patients with combined OTX2 / BMP4 defects [4,12]. Patients 2 and 3 also lacked SIX6 ; however, defects of this candidate gene have not been identified in anophthalmia [1].…”

“…Previous reports of patients with 14q22q23 deletions were inconsistent, varying from not mentioning the hearing status over normal function [7,12] to severe unilateral hearing loss [4,9], indicating very variable expressivity. We speculate that skeletal abnormalities of the facial-cranial junction of the skull associated with anophthalmia due to the OTX2 defect can induce stenosis of ear canals and/or Eustachian tubes and hearing impairment.…”

“…Homozygous knockout of this gene in mice causes malformations of the auditory system including outer ears [14]. Deletions in two published patients also involved SIX1 and were associated with malformed ears, although differently from Patient 2 [4,9]. OTX2 defects themselves could also contribute to ear anomalies [15].…”