BACKGROUND: A clinical case is described of growth retardation, severe developmental delay, facial dysmorphic features with microcephaly, as well as congenital cataract, schizencephaly, periventricular calcifications, and epilepsy. METHODS: TORCH infection was suspected, but all tests for toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus were negative for the child and her mother; however, an increased level of antibodies against parvovirus B19 was detected in the proband. RESULTS: Chromosomal analysis and array-CGH showed no aberration. Target capture sequencing for COL4A1 and COL4A2 revealed a de novo COL4A1 mutation (c.2123G>T [p.Gly708Val]). The mutation occurred at a highly conserved Gly residue in the Gly-X-Y repeat of the collagen triple helical domain, suggesting that these mutations may alter the collagen IV α1α1α2 heterotrimers. The mutation was predicted to be damaging. CONCLUSION: We suggest that COL4A1 testing should be considered in patients with schizencephaly as well as with phenotype suggesting TORCH infection without any proven etiological factors.
BACKGROUND: A clinical case is described of growth retardation, severe developmental delay, facial dysmorphic features with microcephaly, as well as congenital cataract, schizencephaly, periventricular calcifications, and epilepsy. METHODS:TORCH infection was suspected, but all tests for toxoplasmosis, rubella, cytomegalovirus, and herpes simplex virus were negative for the child and her mother; however, an increased level of antibodies against parvovirus B19 was detected in the proband. RESULTS: Chromosomal analysis and array-CGH showed no aberration. Target capture sequencing for COL4A1 and COL4A2 revealed a de novo COL4A1 mutation (c.2123G>T [p.Gly708Val]). The mutation occurred at a highly conserved Gly residue in the Gly-X-Y repeat of the collagen triple helical domain, suggesting that these mutations may alter the collagen IV α1α1α2 heterotrimers. The mutation was predicted to be damaging. CONCLUSION: We suggest that COL4A1 testing should be considered in patients with schizencephaly as well as with phenotype suggesting TORCH infection without any proven etiological factors.
Authors: Sara Zagaglia; Christina Selch; Jelena Radic Nisevic; Davide Mei; Zuzanna Michalak; Laura Hernandez-Hernandez; S Krithika; Katharina Vezyroglou; Sophia M Varadkar; Alexander Pepler; Saskia Biskup; Miguel Leão; Jutta Gärtner; Andreas Merkenschlager; Michaela Jaksch; Rikke S Møller; Elena Gardella; Britta Schlott Kristiansen; Lars Kjærsgaard Hansen; Maria Stella Vari; Katherine L Helbig; Sonal Desai; Constance L Smith-Hicks; Naomi Hino-Fukuyo; Tiina Talvik; Rael Laugesaar; Pilvi Ilves; Katrin Õunap; Ingrid Körber; Till Hartlieb; Manfred Kudernatsch; Peter Winkler; Mareike Schimmel; Anette Hasse; Markus Knuf; Jan Heinemeyer; Christine Makowski; Sondhya Ghedia; Gopinath M Subramanian; Pasquale Striano; Rhys H Thomas; Caroline Micallef; Maria Thom; David J Werring; Gerhard Josef Kluger; J Helen Cross; Renzo Guerrini; Simona Balestrini; Sanjay M Sisodiya Journal: Neurology Date: 2018-11-09 Impact factor: 9.910