Gruhl Sabrina L, Sharma Pankaj, Han Thang S
St George's Hospital Medical School, University of London, London, SW17 0RE, UK.
Institute of Cardiovascular Research, Royal Holloway, University of London, Egham, Surrey, TW20 0EX, UK.
J Med Case Rep. 2018 Nov 28;12(1):353. doi: 10.1186/s13256-018-1863-0.
Cowden's syndrome (OMIM:158350), a rare genetic disorder (incidence ~ 1:250,000), is caused by mutations of the tumor suppressor gene PTEN. In this report, we describe clinical manifestations of a 56-year-old patient diagnosed with Cowden's syndrome and his family with PTEN mutations. The family has an unusually high number of offspring with autism spectrum disorder.
Except for his 80-year-old Caucasian father, all of our index case's living Caucasian kindred (three children, brother, and nephew) had PTEN mutations and macrocephaly. Prior to genetic testing, his mother and sister died of breast cancer at 42 and 38 years old, respectively. After PTEN mutation was identified, our patient underwent complete thyroidectomy (histology showing micropapillary carcinoma) and right nephrectomy for renal cell carcinoma. All of his three children (13-year-old son, 11- and 8-year-old daughters) have been diagnosed with autism spectrum disorder. His son and brother underwent total thyroidectomy. His nephew had thyroid nodules. Management of Cowden's syndrome requires clinical examinations and investigations every 6 to 12 months from 18 years old or 5 years before the family's earliest age of cancer diagnosis and should focus on all clinical manifestations associated with PTEN mutations to identify early abnormal changes in skin, breasts, thyroid, endometrium, gut, and kidneys. Input from specialists across different disciplines is necessary.
We describe a man and his family with PTEN mutations who have increased risk of cancers and an unusually high number of offspring with autism spectrum disorder. Early recognition and close surveillance are vital in order to provide treatment and early screening for asymptomatic at-risk relatives.
考登综合征（OMIM:158350）是一种罕见的遗传性疾病（发病率约为1:250,000），由肿瘤抑制基因PTEN的突变引起。在本报告中，我们描述了一名被诊断为考登综合征的56岁患者及其携带PTEN突变的家族的临床表现。该家族中患有自闭症谱系障碍的后代数量异常之多。
除了我们索引病例80岁的白种人父亲外，我们索引病例的所有在世的白种人亲属（三个孩子、兄弟和侄子）都有PTEN突变和巨头畸形。在进行基因检测之前，他的母亲和姐姐分别在42岁和38岁时死于乳腺癌。在确定PTEN突变后，我们的患者接受了全甲状腺切除术（组织学显示微乳头状癌）和右肾切除术以治疗肾细胞癌。他的三个孩子（13岁的儿子、11岁和8岁的女儿）均被诊断患有自闭症谱系障碍。他的儿子和兄弟接受了全甲状腺切除术。他的侄子有甲状腺结节。考登综合征的管理需要从18岁起或在家族最早癌症诊断年龄前5年开始，每6至12个月进行一次临床检查和调查，并且应关注与PTEN突变相关的所有临床表现，以识别皮肤、乳房、甲状腺、子宫内膜、肠道和肾脏的早期异常变化。需要不同学科专家的参与。
我们描述了一名携带PTEN突变的男性及其家族，他们患癌症的风险增加，且患有自闭症谱系障碍的后代数量异常之多。早期识别和密切监测对于为无症状的高危亲属提供治疗和早期筛查至关重要。
