Khan Arif O, Shinwari Jameela, Al-Sharif Latifa, Khalil Dania S, Al Tassan Nada
Division of Pediatric Ophthalmology, King Khaled Eye Specialist Hospital, Riyadh 11462, Saudi Arabia.
Arch Ophthalmol. 2011 Jul;129(7):936-40. doi: 10.1001/archophthalmol.2011.166.
To determine the genotype underlying suspected X-linked infantile nystagmus in a family and to correlate genotype with clinical examination in potential female carriers.
Ophthalmic examination (ophthalmic, orthoptic, optokinetic [OKN] drum, and electrophysiologic when possible) and candidate gene analysis.
Two affected brothers had infantile nystagmus with no evidence of associated visual or neurological disease. The symptomatic maternal aunt had infantile nystagmus in addition to congenital fibrosis of the extraocular muscles (CFEOM) (bilateral hypotropia, exotropia, ptosis, almost complete ophthalmoplegia, and poorly reactive pupils). A sister, the mother, and the maternal grandmother-all 3 of whom were asymptomatic-had delayed corrective saccades (prolonged pursuit) during OKN drum testing.A brother and the father—both of whom were asymptomatic—had unremarkable examination findings [corrected]. A FRMD7 splice variant (c.1050 + 5 G>A) was identified in the 2 affected brothers and in the 3 asymptomatic women only. Allele sharing analysis further confirmed that the aunt's phenotype was not related to the FRMD7 variant, which was absent in 246 ethnic controls. Her phenotype was also not related to mutation in known CFEOM genes (KIF21A, PHOX2A, TUBB3).
Prolonged pursuit responses during OKN drum testing in asymptomatic female carriers is consistent with the concept of infantile nystagmus being an abnormally increased pursuit oscillation. Further studies are required to determine the reproducibility of this potential female carrier sign. Rather than being FRMD7 related, nystagmus in the maternal aunt represented a second disease in this family, likely related to CFEOM.
Clinicians can use the OKN drum to assess obligate female carriers in a family suspected of having X-linked nystagmus.
确定一个家族中疑似X连锁婴儿型眼球震颤的潜在基因型，并将基因型与潜在女性携带者的临床检查结果相关联。
眼科检查（眼科、斜视矫正、视动[OKN]鼓检查，必要时进行电生理检查）和候选基因分析。
两名患病兄弟患有婴儿型眼球震颤，未发现相关视觉或神经疾病证据。有症状的姨妈除了患有眼外肌先天性纤维化（CFEOM）（双侧下斜视、外斜视、上睑下垂、几乎完全性眼肌麻痹和瞳孔反应迟钝）外，还患有婴儿型眼球震颤。一个姐妹、母亲和外祖母——这三人均无症状——在OKN鼓检查期间出现矫正性扫视延迟（追踪延长）。一个兄弟和父亲——两人均无症状——检查结果正常[校正后]。在两名患病兄弟和三名无症状女性中仅发现一种FRMD7剪接变体（c.1050 + 5 G>A）。等位基因共享分析进一步证实，姨妈的表型与FRMD7变体无关，该变体在246名种族对照中不存在。她的表型也与已知CFEOM基因（KIF21A、PHOX2A、TUBB3）的突变无关。
无症状女性携带者在OKN鼓检查期间出现追踪反应延长，这与婴儿型眼球震颤是追踪振荡异常增加的概念一致。需要进一步研究以确定这种潜在女性携带者体征的可重复性。姨妈的眼球震颤并非与FRMD7相关，而是代表该家族中的第二种疾病，可能与CFEOM有关。
临床医生可使用OKN鼓评估疑似患有X连锁眼球震颤家族中的必然女性携带者。
