Glaucoma is defined by characteristic optic nerve damage and corresponding visual field defects and is the leading cause of irreversible blindness in the world. Elevated intraocular pressure (IOP) is a strong risk factor for developing glaucoma. However, glaucoma can occur at any IOP. Normal tension glaucoma (NTG) arises with IOPs that are within what has been defined as a normal range, i.e., 21 mm Hg or less, which may present challenges in its diagnosis and management. Identifying inheritance patterns and genetic mutations in families with NTG has helped elucidate mechanisms of NTG, however the pathophysiology is complex and not fully understood. Approximately 2% of NTG cases are caused primarily by mutations in single genes, optineurin (OPTN), TANK binding kinase 1 (TKB1), or myocilin (MYOC). Herein, we review pedigree studies of NTG and autosomal dominant NTG caused by OPTN, TBK1, and MYOC mutations. We review identified mutations and resulting clinical features of OPTN-associated and TBK1-associated NTG, including long-term follow up of these patients with NTG. In addition, we report a new four-generation pedigree of NTG caused by a Glu50Lys OPTN mutation, including six family members with a mean follow up of 17 years. Common features of OPTN -associated NTG due to Glu50Lys mutation included early onset of disease with an IOP <21 mm Hg, marked optic disc cupping, and progressive visual field loss which appeared to stabilize once an IOP of less than 10 mm Hg was achieved. Lastly, we review risk factor genes which have been identified to contribute to the complex inheritance of NTG.

青光眼的定义是特征性视神经损伤和相应的视野缺陷，是世界上不可逆失明的主要原因。眼内压（IOP）升高是发生青光眼的一个重要危险因素。然而，任何眼压都可能发生青光眼。正常眼压性青光眼(NTG) 的眼压在定义为正常范围内（即 21 毫米汞柱或更低）时出现，这可能对其诊断和治疗提出挑战。识别 NTG 家族的遗传模式和基因突变有助于阐明 NTG 的机制，但其病理生理学很复杂且尚未完全了解。大约 2% 的 NTG 病例主要由单基因、optineurin ( OPTN )、TANK 结合激酶 1 ( TKB1 ) 或肌纤蛋白 ( MYOC )突变引起。在此，我们回顾了由OPTN、TBK1和MYOC突变引起的 NTG 和常染色体显性 NTG 的家系研究。我们回顾了OPTN相关和TBK1相关 NTG的已识别突变和由此产生的临床特征，包括对这些 NTG 患者的长期随访。此外，我们报告了由 Glu50Lys OPTN突变引起的 NTG 新四代谱系，其中包括 6 名家族成员，平均随访时间为 17 年。Glu50Lys 突变导致的 OPTN 相关 NTG 的共同特征包括疾病早期发作，眼压<21 mm Hg、明显的视盘杯状以及进行性视野丧失，一旦眼压低于 10 mm Hg，视野丧失似乎会稳定下来。最后，我们回顾了已确定有助于 NTG 复杂遗传的风险因素基因。