Abstract：
BACKGROUND: Hereditary cranial hyperostosis is a rare disease never described in Italy, so the neurological manifestations in patients and carriers of the disease have been little studied.
METHODS: We describe the neurological and neuroimaging features of patients and carriers of the gene from a large Italian family with sclerosteosis.
RESULTS: In this family, genetic testing detected the homozygous p.Gln24X (c.70C > T) mutation of the SOST gene in the proband and a heterozygous mutation in 9 siblings. In homozygous adults, severe craniofacial hyperostosis was manifested by cranial neuropathy in childhood, chronic headache secondary to intracranial hypertension, and an obstructive sleep apnea syndrome in adults. In one of the adult patients, there was a compressible subcutaneous swelling in the occipital region caused by transosseous intracranial-extracranial occipital venous drainage, a compensation mechanism of obstructed venous drainage secondary to cranial hyperostosis. Mild cranial hyperostosis causing frequent headache and snoring was evident in the nine heterozygous subjects.
CONCLUSIONS: Multiple cranial neuropathies and headache in children, while severe chronic headache and sleep disturbances in adults, are the neurological manifestations of the first Italian family with osteosclerosis. It is reasonable to extend neurological and neuroimaging evaluation to gene carriers as well.
METHODS: We describe the neurological and neuroimaging features of patients and carriers of the gene from a large Italian family with sclerosteosis.
RESULTS: In this family, genetic testing detected the homozygous p.Gln24X (c.70C > T) mutation of the SOST gene in the proband and a heterozygous mutation in 9 siblings. In homozygous adults, severe craniofacial hyperostosis was manifested by cranial neuropathy in childhood, chronic headache secondary to intracranial hypertension, and an obstructive sleep apnea syndrome in adults. In one of the adult patients, there was a compressible subcutaneous swelling in the occipital region caused by transosseous intracranial-extracranial occipital venous drainage, a compensation mechanism of obstructed venous drainage secondary to cranial hyperostosis. Mild cranial hyperostosis causing frequent headache and snoring was evident in the nine heterozygous subjects.
CONCLUSIONS: Multiple cranial neuropathies and headache in children, while severe chronic headache and sleep disturbances in adults, are the neurological manifestations of the first Italian family with osteosclerosis. It is reasonable to extend neurological and neuroimaging evaluation to gene carriers as well.
摘要：
背景：遗传性颅骨肥大是一种在意大利从未描述过的罕见疾病，因此，很少研究该疾病患者和携带者的神经系统表现。
方法：我们描述了来自意大利一个患有硬化病的大型家庭的患者和基因携带者的神经和神经影像学特征。
结果：在这个家族中，遗传测试检测到先证者中SOST基因的纯合p.Gln24X（c.70C>T）突变和9个兄弟姐妹中的杂合突变。在纯合成人中，严重的颅面骨肥厚在儿童时期表现为颅神经病,继发于颅内高压的慢性头痛，和成人阻塞性睡眠呼吸暂停综合征。在一个成年患者中，枕区有一个可压缩的皮下肿胀，由经骨颅内-颅外枕静脉引流引起，继发于颅骨肥厚的静脉引流阻塞的补偿机制。在9名杂合子受试者中，轻度颅骨增生引起频繁的头痛和打鼾。
结论：儿童多发性颅神经病和头痛，而成人严重的慢性头痛和睡眠障碍，是第一个患有骨硬化的意大利家庭的神经系统表现。将神经和神经影像学评估扩展到基因携带者也是合理的。
方法：我们描述了来自意大利一个患有硬化病的大型家庭的患者和基因携带者的神经和神经影像学特征。
结果：在这个家族中，遗传测试检测到先证者中SOST基因的纯合p.Gln24X（c.70C>T）突变和9个兄弟姐妹中的杂合突变。在纯合成人中，严重的颅面骨肥厚在儿童时期表现为颅神经病,继发于颅内高压的慢性头痛，和成人阻塞性睡眠呼吸暂停综合征。在一个成年患者中，枕区有一个可压缩的皮下肿胀，由经骨颅内-颅外枕静脉引流引起，继发于颅骨肥厚的静脉引流阻塞的补偿机制。在9名杂合子受试者中，轻度颅骨增生引起频繁的头痛和打鼾。
结论：儿童多发性颅神经病和头痛，而成人严重的慢性头痛和睡眠障碍，是第一个患有骨硬化的意大利家庭的神经系统表现。将神经和神经影像学评估扩展到基因携带者也是合理的。
