Genetic Unit, Department of Obstetrics and Gynecology, Centro de Educación Médica en Investigaciones Clínicas, CEMIC, Instituto Universitario, Buenos Aires, Argentina.
Prenat Diagn. 2011 Sep;31(9):887-91. doi: 10.1002/pd.2796. Epub 2011 Jun 27.
To assess the likelihood of finding an etiopathogenic cause in an ultrasonographic prenatal diagnosis of holoprosencephaly.
From January 1996 to June 2010, 13 883 prenatal diagnoses through chorionic villus sampling or amniocentesis were made. Every fetus with holoprosencephaly at ultrasound was evaluated. Gestational age, additional ultrasound findings, and fetal karyotype were recorded. Molecular diagnosis and parental karyotype were studied, if relevant.
Twenty-eight fetuses were diagnosed with holoprosencephaly (0.20%). All cases had additional ultrasound findings (100%). A definitive etiology was found in 23 cases (82.14%): karyotype was abnormal in 19 (67.9%) and normal in 8 (28.5%) cases. In the normal karyotype group, although molecular testing was performed in a few cases, one mutation of gene SIX 3 was diagnosed, one diagnosis of dysgnathia complex was made, and two fetuses presented Smith-Lemli-Opitz syndrome. No etiopathogenic diagnosis was made in five fetuses.
Our results showed that a definitive etiology can be established in most cases of prenatal holoprosencephaly. Chromosomal anomalies were the most frequent finding. However, in euploid fetuses, molecular diagnosis is worthwhile, as different genes with different inheritance patterns may be responsible for this malformation. Thorough evaluation proved beneficial for assessing more accurate prognosis and recurrence risks.
评估在产前超声诊断全前脑畸形中发现病因的可能性。
1996 年 1 月至 2010 年 6 月，通过绒毛膜取样或羊膜穿刺术进行了 13883 次产前诊断。对每一例超声检查发现全前脑畸形的胎儿进行评估。记录胎儿的胎龄、额外的超声表现和胎儿核型。如果相关，进行分子诊断和父母核型分析。
28 例胎儿被诊断为全前脑畸形（0.20%）。所有病例均有额外的超声表现（100%）。23 例（82.14%）明确了病因：19 例（67.9%）核型异常，8 例（28.5%）核型正常。在核型正常的组中，尽管对少数病例进行了分子检测，但发现了一个 SIX3 基因突变，一个诊断为面骨发育不良综合征，两个胎儿表现为 Smith-Lemli-Opitz 综合征。5 例未明确病因。
我们的结果表明，大多数产前全前脑畸形病例可以确定病因。染色体异常是最常见的发现。然而，在正常核型的胎儿中，进行分子诊断是有价值的，因为不同的基因可能以不同的遗传方式导致这种畸形。全面评估有助于更准确地评估预后和复发风险。
