Prenatal Diagnosis of Lissencephaly Associated with Biallelic Pathologic Variants in the COQ2 Gene.

Primary CoQ10 deficiency comprises several clinical phenotypes. Nevertheless, there are no reports so far of lissencephaly linked to CoQ10 deficiency. Lissencephaly is a developmental condition associated with defective neuronal migration which may be depicted on fetal neurosonography by persistence of a laminar pattern beyond 34 weeks and abnormal cortical sulcation. We report an index case of a male fetus diagnosed with abnormal lamination, characterized by the persistence of a laminar pattern during late pregnancy, following a normal second trimester scan. Post-natal whole exome sequencing revealed biallelic pathologic variants in the COQ2 gene which encodes an enzyme that is part of coenzyme Q10 (COQ10 or ubiquinone) pathway and is involved in the biosynthesis of CoQ, a redox carrier in the mitochondrial respiratory chain and a lipid-soluble antioxidant. This case underscores the heterogeneity of the prenatal phenotypic presentation of pathogenic variants in the COQ2, namely lissencephaly.

A deficiência primária de CoQ10 traduz-se numa variedade de fenótipos clínicos. Todavia, não existe até à data nenhuma descrição deste défice associado a lisencefalia. A lisencefalia consiste numa alteração do desenvolvimento cortical cerebral em que se verifica um defeito na migração neuronal, detetável na neurossonografia pela persistência de um padrão de laminação cerebral após as 34 semanas de gestação e por alterações nas circunvoluções corticais. Neste trabalho descreve-se o caso de um feto masculino com um padrão de laminação cerebral alterado, detetado na avaliação ecográfica do terceiro trimestre, após exame morfológico sem alterações. A sequenciação pós-natal do exoma revelou uma variante bialélica patológica do gene COQ2, que codifica uma enzima da via da coenzima Q10 (COQ10 ou ubiquinona), envolvida na biossíntese do CoQ, um transportador redox da cadeia respiratória mitocondrial e anti-oxidante lipossolúvel. Com este caso, destaca-se a heterogeneidade fenotípica pré-natal das variantes patogénicas no gene COQ2.

Premature or Small for Gestational Age Discrimination: International Multicenter Trial Protocol for Classification of the Low-Birth-Weight Newborn Through the Optical Properties of the Skin.

BACKGROUND: A low birth weight is an independent risk factor for adverse infant outcomes and a predictor of chronic disease in adulthood. In these situations, differentiating between prematurity and small for gestational age (SGA) or simultaneous conditions is essential to ensuring adequate care. Such diagnoses, however, depend on reliable pregnancy dating, which can be challenging in developing countries. A new medical optoelectronic device was developed to estimate gestational age (GA) at birth based on newborn skin reflection. OBJECTIVE: This study will aim to evaluate the device's ability to detect prematurity or SGA, or both conditions simultaneously as well as predict short-term pulmonary complications in a cohort of low-birth-weight newborns. METHODS: This study protocol was designed for a multicenter cohort including referral hospitals in Brazil and Mozambique. Newborns weighing 500-2500 g will be eligible for inclusion with the best GA available, considering the limited resources of low-income countries. Comparator-GA is based on reliable last menstrual period dating or ultrasound assessment before 24 weeks' gestation. Estimated GA at birth (Test-GA) will be calculated by applying a novel optoelectronic device to the newborn's skin over the sole. The average difference between Test-GA and Comparator-GA will be analyzed, as will the percentage of newborns who are correctly diagnosed as preterm or SGA. In addition, in a nested case-control study, the accuracy of skin reflection in the prediction of prematurity-related respiratory problems will be evaluated. The estimated required sample size is 298 newborns. RESULTS: Teams of health professionals were trained, and standard operating procedures were developed following the good practice guidelines for the clinical investigation of medical devices for human participants. The first recruitment started in March 2019 in Brazil. Data collection is planned to end in December 2020, and the results should be available in March 2021. CONCLUSIONS: The results of this clinical study have the potential to validate a new device to easily assess postnatal GA, supporting SGA identification when pregnancy dating is unreliable or unknown. TRIAL REGISTRATION: ReBec: RBR-33rnjf; http://www.ensaiosclinicos.gov.br/rg/RBR-33rnjf/. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/16477.