Lissencephaly With Bilateral Complete Cleft Lip and Palate: An Early Second‐Trimester Diagnosis

The lissencephalies are a group of disorders characterized by the paucity of gyral and sulcal formation known as agyria and pachygyria resulting from abnormal neuronal migration between about 8 to 14 weeks’ gestation. We report an antenatally diagnosed unique case of lissencephaly with severe cerebellar hypoplasia and bilateral complete cleft lip and palate. Although lissencephaly syndromes can rarely be associated with cleft lip and palate,1 antenatal diagnosis has not been reported in the current literature to date. Transvaginal sonography helped us confirm the lissencephaly more confidently. A 22-year-old primigravid undergoing a routine antenatal checkup in the second trimester had a single live intrauterine fetus of approximately 24 weeks’ gestational age in the cephalic presentation. A mild discrepancy was noted between the gestational age and the menstrual age, with a difference of about 1 to 1.5 weeks. Sonography of the fetal brain revealed mildly dilated parallel oriented lateral ventricles with absence of the parieto-occipital fissure from the expected location on the medial hemispheric surface and a smooth, shallow sylvian fissure. The posterior fossa appeared small with cerebellar hypoplasia. There was a mild kyphotic deformity noted at the thoracolumbar region. The rest of the fetal scan was unremarkable. Twoand three-dimensional sonography of the fetal face showed bilateral complete cleft lip and palate, a prominent nose and premaxillary protrusion, a depressed nasal bridge, and hyperteleorism (Figure 1, A and B). Transvaginal sonography was performed after written patient consent and revealed complete absence of the corpus callosum, cingulate sulcus, and convex sulci (Figure 1C). After all of the findings were considered, a diagnosis of lissencephaly with corpus callosal agenesis and cleft lip and palate was made. Maternal screening was done for the TORCH group of infections (toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus), the results of which were negative. In view of the severe anomalies, the pregnancy was terminated, and a stillborn fetus was delivered. On postnatal examination, bilateral complete cleft lip and palate, a prominent nose, and hyperteleorism were noted. Mild kyphosis was noted on plain radiography. No other obvious external abnormalities were noted. Postnatal neurosonography and magnetic resonance imaging showed complete absence of cortical sulci (agyria), a shallow sylvian fissure with a figure 8 appearance, complete corpus callosal agenesis with colpocephaly, and severe cerebellar and vermian hypoplasia, thus confirming the antenatal findings (Figure 1D). The parents refused consent for autopsy and genetic testing. Lissencephaly is often not diagnosed until childhood, and most patients have severe developmental delays, microcephaly, intractable seizures, and premature death. Classic lissencephaly is a brain malformation caused by abnormal neuronal migration between 9 and 13 weeks’ gestation, resulting in a spectrum of agyria, mixed agyria/pachygyria, and pachygyria. It is characterized by an abnormally thick and poorly organized cortex with 4 primitive layers, diffuse neuronal heterotopia, enlarged and dysmorphic ventricles, and often hypoplasia of the corpus callosum.2 Classic lissencephaly includes lissencephaly secondary to mutations in the lissencephaly 1 gene (locus at 17p13.3, subset of the group with chromosome 17 mutations, having characteristic facies and classified as MillerDieker syndrome) and doublecortin gene (also called the X-linked lissencephaly gene, at chromosome Xq22.3q23).3 Miller-Dieker syndrome (17p13 deletion) has lissencephaly combined with dysmorphic facial features