Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors.

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.

Impotence in diabetics: organic versus psychogenic factors.

Four types of impotence were diagnosed in 75 consecutive impotent diabetic patients: chronic persistent organic type due to vascular and/or neurologic factors (44%), temporary organic types due to medical illness other than diabetes (10.6%) or uncontrolled metabolic state (6.6%), and psychogenic impotence (38.6%). Despite higher incidence of organic etiology (61.3%) the incidence of psychogenic impotence was significant. None of the methods used to diagnose the type of impotence in the present study proved 100 per cent accurate, and we advise a combination of history-taking including the wife's history, physical examination including vascular and neurologic tests, nocturnal penile tumescence studies, and therapeutic trials with sex therapy to differentiate between true organic, temporary organic, and psychogenic types of impotence in diabetic patients. This differentiation is mandatory since the latter two types may have a better prognosis.

Experience with the classification, diagnosis, and therapy of nonejaculatory intercourse.

Twenty-one consecutive patients complaining of nonejaculatory intercourse were studied. Fifteen patients had anejaculation of various types, and sex therapy succeeded in 4 of 7 cases. Three patients had retrograde ejaculation that could be corrected by ephedrine sulfate in two cases having a neurologic cause. In one of three patients having nonemission, ejaculation was restored after stopping the drug thioridazine. A juvenile diabetic patient was discovered to have nonemission and not retrograde ejaculation. A classification of the disorders leading to nonejaculatory intercourse based on pathogenetic and clinical data is presented, including anejaculation, retrograde ejaculation, nonemission, and aspermia.