Heterozygous 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. 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 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. 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.

中文翻译：

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一例女性 L1 综合征病例，可能是由于 X 失活偏斜所致

杂合变异导致 L1 综合征，伴有脑积水和胼胝体发育不全/发育不全。L1综合征通常具有X连锁隐性遗传模式；然而，我们报告了一个发生在女孩身上的罕见病例。该患者的家族史无异常。胎儿超声检查显示双侧脑室增大和胼胝体发育不全。患者在妊娠 38 周零 4 天时出生。出生后第 8 天进行的脑部 MRI 检查显示脑室增大，侧脑室和第三脑室边缘不规则，胼胝体发育不全。2 岁零 3 个月时的外显子组测序揭示了从头杂合变异 (NM_000425.5: c.2934_2935delp. (His978Glnfs * 25)。使用人类雄激素受体测定的 X 染色体失活揭示了 X 染色体的模式患者中的失活高度倾斜（96.6%）。患者现在 4 岁 11 个月大，有轻度发育迟缓（发育商数，56），脑积水没有显着进展。在这种情况下，我们假设显性表达X 失活偏斜引起的变异等位基因可能导致 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。