From the Department of Surgery, Section of Plastic Surgery, Yale School of Medicine.
Plast Reconstr Surg. 2020 Jan;145(1):117e-125e. doi: 10.1097/PRS.0000000000006319.
De novo or rare transmitted mutations in the SMAD6 gene affect 7 percent of midline nonsyndromic synostosis patients. This study aimed to determine the neurocognitive sequelae of SMAD6 synostosis.
Nonsyndromic synostosis patients 6 years or older with SMAD6 mutations and non-SMAD6 nonsyndromic synostosis controls were recruited. All patients completed a double-blinded neurodevelopmental battery (i.e., Wechsler Fundamentals, Wechsler Abbreviated Scale of Intelligence, Beery-Buktenica Developmental test), and parents/guardians completed behavioral surveys (Behavior Rating Inventory of Executive Function and Behavior Rating System for Children).
Twenty-eight patients participated: 10 known SMAD6 patients (average age, 10 years; 1 female; eight metopic and two sagittal; nine treated with cranial vault remodeling and one treated with strip craniectomy) and 18 non-SMAD6 controls (age, 9.5 years; three female; 12 metopic and six sagittal; 17 treated with cranial vault remodeling and one treated with strip craniectomy). There were no differences between any demographics. Testing age, surgical age, parental education, and household income correlated with cognition (p < 0.05). After controlling for these factors, SMAD6 patients performed worse on numerical operations (p = 0.046), performance intelligence quotient (p = 0.018), full-scale intelligence quotient (p = 0.010), and motor coordination (p = 0.043) compared to age/race/gender/synostosis/operation-matched controls. On behavioral surveys, SMAD6 patients scored worse on 14 assessments, including aggression, communication, and behavior.
This prospective double-blinded study revealed that neuropsychiatric development of nonsyndromic synostosis may be under genetic control. SMAD6 mutations led to poorer mathematics, performance intelligence quotient, full-scale intelligence quotient, and motor coordination, even after controlling for exogenous factors. Genetic testing may be critical for advocating early adjunctive neurodevelopmental therapy.
CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.
SMAD6 基因中的从头或罕见的传递突变影响了 7%的中线非综合征颅缝早闭患者。本研究旨在确定 SMAD6 颅缝早闭的神经认知后遗症。
招募了年龄在 6 岁及以上的 SMAD6 突变型非综合征性颅缝早闭患者和非 SMAD6 非综合征性颅缝早闭对照者。所有患者均完成了双盲神经发育测试（即韦氏基本智力量表、韦氏简明智力量表、比耶里-布克蒂卡发展测试），家长/监护人完成了行为调查（执行功能行为评定量表和儿童行为评定系统）。
28 名患者参与了研究：10 名已知的 SMAD6 患者（平均年龄 10 岁，1 名女性，8 名矢状缝早闭，2 名冠状缝早闭，9 名接受了颅骨成形术，1 名接受了颅骨切除术）和 18 名非 SMAD6 对照组（年龄 9.5 岁，3 名女性，12 名矢状缝早闭，6 名冠状缝早闭，17 名接受了颅骨成形术，1 名接受了颅骨切除术）。在任何人口统计学方面都没有差异。测试年龄、手术年龄、父母教育程度和家庭收入与认知能力相关（p<0.05）。在控制了这些因素后，SMAD6 患者在数字运算（p=0.046）、表现智商（p=0.018）、全智商（p=0.010）和运动协调能力（p=0.043）方面的表现明显差于年龄/种族/性别/颅缝早闭/手术匹配的对照组。在行为调查中，SMAD6 患者在 14 项评估中得分较低，包括攻击行为、沟通能力和行为问题。
这项前瞻性双盲研究表明，非综合征性颅缝早闭的神经精神发育可能受到遗传控制。SMAD6 突变导致了更差的数学、表现智商、全智商和运动协调能力，即使在控制了外源性因素后也是如此。基因检测对于提倡早期辅助神经发育治疗可能至关重要。
临床问题/证据水平：风险，II 级。
