ABSTRACT
BACKGROUND AND PURPOSE: Pathogenic somatic variants affecting the genes Histone 3 Family 3A and 3B (H3F3) are extensively linked to the process of oncogenesis, in particular related to central nervous system tumors in children. Recently, H3F3 germline missense variants were described as the cause of a novel pediatric neurodevelopmental disorder. We aimed to investigate patterns of brain MR imaging of individuals carrying H3F3 germline variants. MATERIALS AND METHODS: In this retrospective study, we included individuals with proved H3F3 causative genetic variants and available brain MR imaging scans. Clinical and demographic data were retrieved from available medical records. Molecular genetic testing results were classified using the American College of Medical Genetics criteria for variant curation. Brain MR imaging abnormalities were analyzed according to their location, signal intensity, and associated clinical symptoms. Numeric variables were described according to their distribution, with median and interquartile range. RESULTS: Eighteen individuals (10 males, 56%) with H3F3 germline variants were included. Thirteen of 18 individuals (72%) presented with a small posterior fossa. Six individuals (33%) presented with reduced size and an internal rotational appearance of the heads of the caudate nuclei along with an enlarged and squared appearance of the frontal horns of the lateral ventricles. Five individuals (28%) presented with dysgenesis of the splenium of the corpus callosum. Cortical developmental abnormalities were noted in 8 individuals (44%), with dysgyria and hypoplastic temporal poles being the most frequent presentation. CONCLUSIONS: Imaging phenotypes in germline H3F3-affected individuals are related to brain features, including a small posterior fossa as well as dysgenesis of the corpus callosum, cortical developmental abnormalities, and deformity of lateral ventricles.
Subject(s)
Brain Neoplasms , Histones , Malformations of Cortical Development , Neurodevelopmental Disorders , Brain/diagnostic imaging , Brain/pathology , Brain Neoplasms/diagnostic imaging , Brain Neoplasms/genetics , Brain Neoplasms/pathology , Child , Germ Cells/pathology , Histones/genetics , Humans , Male , Malformations of Cortical Development/pathology , Neurodevelopmental Disorders/pathology , Retrospective StudiesABSTRACT
We present 12 children with typical Brachmann-de Lange syndrome and congenital diaphragmatic hernia. Affected children were more likely to be of low birth weight and to have major upper limb malformations. Hernia repair was attempted in 4 of these children, and only one survived past 12 months. Newborn infants with congenital diaphragmatic hernia should be examined carefully for evidence of the Brachmann-de Lange syndrome because diagnosis of this condition may influence their clinical management and prognosis.
Subject(s)
De Lange Syndrome/diagnosis , Hernias, Diaphragmatic, Congenital , De Lange Syndrome/genetics , De Lange Syndrome/pathology , Female , Hernia, Diaphragmatic/genetics , Humans , Infant , Infant, Newborn , Limb Deformities, Congenital , Male , Phenotype , PrognosisABSTRACT
Dermatoglyphic findings were compared in 42 patients (32 females, 10 males) with Congenital Adrenal Hyperplasia (CAH) and 110 normal controls (70 females, 40 males). In CAH males, an excess of whorls (p less than 0.001), an increased total finger ridge count (p less than 0.05), and an increased frequency of patterns in the fourth interdigital area (p less than 0.025) was found. A main line A terminating high in the hypothenar area (p less than 0.05), and a missing c-triradius or an abortive main line C (p less than 0.05) was observed in CAH females. Both sexes displayed an increase in the frequency of small radially directed hypothenar patterns (p less than 0.05) and sydney lines (p less than 0.01).
