Abstract：
BACKGROUND: Heterozygous L1CAM variants cause L1 syndrome with hydrocephalus and aplasia/hypoplasia of the corpus callosum. L1 syndrome usually has an X-linked recessive inheritance pattern; however, we report a rare case occurring in a female child.
METHODS: The patient\'s family history was unremarkable. Fetal ultrasonography revealed enlarged bilateral ventricles of the brain and hypoplasia of the corpus callosum. The patient was born at 38 weeks and 4 days of gestation. Brain MRI performed on the 8th day of life revealed enlargement of the brain ventricles, marked in the lateral and third ventricles with irregular margins, and hypoplasia of the corpus callosum. Exome sequencing at the age of 2 years and 3 months revealed a de novo heterozygous L1CAM variant (NM_000425.5: c.2934_2935delp. (His978Glnfs * 25). X-chromosome inactivation using the human androgen receptor assay revealed that the pattern of X-chromosome inactivation in the patients was highly skewed (96.6 %). The patient is now 4 years and 11 months old and has a mild developmental delay (developmental quotient, 56) without significant progression of hydrocephalus.
CONCLUSIONS: In this case, we hypothesized that the dominant expression of the variant allele arising from skewed X inactivation likely caused L1 syndrome. Symptomatic female carriers may challenge the current policies of prenatal and preimplantation diagnoses.
METHODS: The patient\'s family history was unremarkable. Fetal ultrasonography revealed enlarged bilateral ventricles of the brain and hypoplasia of the corpus callosum. The patient was born at 38 weeks and 4 days of gestation. Brain MRI performed on the 8th day of life revealed enlargement of the brain ventricles, marked in the lateral and third ventricles with irregular margins, and hypoplasia of the corpus callosum. Exome sequencing at the age of 2 years and 3 months revealed a de novo heterozygous L1CAM variant (NM_000425.5: c.2934_2935delp. (His978Glnfs * 25). X-chromosome inactivation using the human androgen receptor assay revealed that the pattern of X-chromosome inactivation in the patients was highly skewed (96.6 %). The patient is now 4 years and 11 months old and has a mild developmental delay (developmental quotient, 56) without significant progression of hydrocephalus.
CONCLUSIONS: In this case, we hypothesized that the dominant expression of the variant allele arising from skewed X inactivation likely caused L1 syndrome. Symptomatic female carriers may challenge the current policies of prenatal and preimplantation diagnoses.
摘要：
背景：杂合型L1CAM变异体可导致L1综合征伴脑积水和call体发育不全/发育不全。L1综合征通常具有X连锁隐性遗传模式；然而，我们报告一例罕见的病例发生在一名女性儿童身上。
方法：患者家族史无异常。胎儿超声检查显示大脑双侧心室扩大和call体发育不全。患者在妊娠38周零4天出生。在生命的第8天进行的脑部MRI显示脑室扩大，在侧脑室和第三脑室有不规则的边缘，和call体发育不全。2岁零3个月大的外显子组测序显示了从头杂合的L1CAM变体（NM_000425.5：c.2934_2935delp。（His978Glnfs*25）。使用人类雄激素受体测定的X染色体失活表明，患者的X染色体失活模式高度偏斜（96.6％）。患者现在4岁零11个月大，有轻度发育迟缓（发育商，56)无显著进展的脑积水。
结论：在这种情况下，我们假设由X偏斜失活引起的变异等位基因的显性表达可能导致L1综合征.有症状的女性携带者可能会挑战当前的产前和植入前诊断政策。
方法：患者家族史无异常。胎儿超声检查显示大脑双侧心室扩大和call体发育不全。患者在妊娠38周零4天出生。在生命的第8天进行的脑部MRI显示脑室扩大，在侧脑室和第三脑室有不规则的边缘，和call体发育不全。2岁零3个月大的外显子组测序显示了从头杂合的L1CAM变体（NM_000425.5：c.2934_2935delp。（His978Glnfs*25）。使用人类雄激素受体测定的X染色体失活表明，患者的X染色体失活模式高度偏斜（96.6％）。患者现在4岁零11个月大，有轻度发育迟缓（发育商，56)无显著进展的脑积水。
结论：在这种情况下，我们假设由X偏斜失活引起的变异等位基因的显性表达可能导致L1综合征.有症状的女性携带者可能会挑战当前的产前和植入前诊断政策。
