Innes A Micheil, Neufeld Stanley, Dyment David A
Department of Medical Genetics, University of Calgary;, Alberta Children's Hospital Research Institute for Child and Maternal Health, Calgary, Alberta, Canada
Department of Medical Genetics, University of Calgary, Calgary, Alberta, Canada
-related SHORT syndrome is a mnemonic for hort stature, yperextensibility, cular depression (deep-set eyes), ieger anomaly, and eething delay. It is now recognized that the features most consistently observed in -related SHORT syndrome are a characteristic facial gestalt (triangular face, broad forehead, deep-set eyes, narrow nasal tip, thin nasal alae, low-hanging columella, downturned corners of the mouth, chin dimple, and prominent ears), delayed dentition, mild intrauterine growth restriction, mild-to-moderate short stature, and partial lipodystrophy (evident in the face and later in the chest and upper extremities, often sparing the buttocks and legs). Insulin resistance may be evident in mid-childhood or adolescence, although diabetes mellitus typically does not develop until early adulthood. Other frequent features include Axenfeld-Rieger anomaly or related ocular anterior chamber dysgenesis, vision issues, other dental issues, and sensorineural hearing loss. Cardiac anomalies, connective tissue findings (joint laxity, inguinal hernia), and frequent infections have also been reported.
DIAGNOSIS/TESTING: The diagnosis of -related SHORT syndrome is established in a proband with characteristic clinical features and a heterozygous pathogenic variant in identified by molecular genetic testing.
Treatment for glucose intolerance and diabetes mellitus per endocrinologist; glaucoma treatment by ophthalmologist to reduce and stabilize intraocular pressure and preserve vision; standard management for other ocular findings; treatment for dental anomalies may include crowns and dental prostheses; standard hearing aids for sensorineural hearing loss; speech therapy as needed; treatment of cardiac anomalies per cardiologist; standard treatments for joint laxity, inguinal hernia, and frequent infections. Assess growth including height, weight, and body mass index every six to 12 months; screening for insulin resistance by oral glucose tolerance test every five years in the absence of diabetes; fasting glucose, insulin, and hemoglobin A1c annually beginning at age ten years; eye examinations to include measurement of intraocular pressure annually; dental examination every six months; hearing assessment every two to three years; assess for joint laxity, hernias, and frequent infections annually. Administration of human growth hormone as it may exacerbate insulin resistance. Three individuals with -related SHORT syndrome had worsening insulin resistance when treated with metformin. If present, diabetes mellitus is managed as appropriate.
-related SHORT syndrome is inherited in an autosomal dominant manner. Some individuals diagnosed with -related SHORT syndrome have an affected parent; 70% of affected individuals have the disorder as the result of a pathogenic variant. Each child of an individual with -related SHORT syndrome has a 50% chance of inheriting the pathogenic variant. Once the pathogenic variant has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.
SHORT综合征是身材矮小（hort stature）、关节过度伸展（yperextensibility）、眼球内陷（cular depression，深陷的眼睛）、里格尔异常（ieger anomaly）和出牙延迟（eething delay）的首字母缩写。现在人们认识到，SHORT综合征中最常观察到的特征是轻度宫内生长受限（IUGR）；轻度至中度身材矮小；部分脂肪营养不良（面部明显，随后胸部和上肢出现，臀部和腿部通常不受影响）；以及特征性面部形态。胰岛素抵抗可能在儿童中期或青春期明显，尽管糖尿病通常直到成年早期才会发展。其他常见特征包括阿克森费尔德-里格尔异常或相关的眼前房发育异常、出牙延迟和其他牙齿问题，以及感音神经性听力损失。
诊断/检测：SHORT综合征的诊断是在具有符合临床特征（重点是面部形态）且通过分子基因检测鉴定出杂合致病变异的先证者中确立的。
青光眼：降低并稳定眼压以保护视力。感音神经性听力损失：使用助听器。牙齿异常：进行标准治疗；可能包括牙冠和假牙。糖耐量异常和糖尿病：由内分泌专家随访。定期监测生长情况，包括身高、体重和体重指数。对于所有有或无明显前房异常的个体：进行常规眼部检查，包括测量眼压。每两到三年进行听力评估。在无糖尿病的情况下，每五年通过口服葡萄糖耐量试验筛查胰岛素抵抗。10岁后开始每年进行糖尿病筛查实验室检查。使用人生长激素可能会加重胰岛素抵抗。一名SHORT综合征患者在使用二甲双胍治疗时胰岛素抵抗恶化；需要进一步研究以确定该药物的影响。如果存在糖尿病，则进行适当管理。
SHORT综合征以常染色体显性方式遗传。由致病变异引起的SHORT综合征患者的比例尚不清楚，但似乎相当可观。SHORT综合征患者的每个孩子都有50%的机会继承致病变异。如果在受影响的家庭成员中已鉴定出致病变异，则对风险增加的妊娠进行产前检测和植入前基因检测是可行的。
