Developmental malformations in Huntington disease: neuropathologic evidence of focal neuronal migration defects in a subset of adult brains

Neuropathologic hallmarks of Huntington Disease (HD) include the progressive neurodegeneration of the striatum and the presence of Huntingtin (HTT) aggregates that result from abnormal polyQ expansion of the HTT gene. Whether the pathogenic trinucleotide repeat expansion of the HTT gene causes neurodevelopmental abnormalities has garnered attention in both murine and human studies; however, documentation of discrete malformations in autopsy brains of HD individuals has yet to be described. We retrospectively searched the New York Brain Bank (discovery cohort) and an independent cohort (validation cohort) to determine whether developmental malformations are more frequently detected in HD versus non-HD brains and to document their neuropathologic features. One-hundred and thirty HD and 1600 non-HD whole brains were included in the discovery cohort and 720 HD and 1989 non-HD half brains were assessed in the validation cohort. Cases with developmental malformations were found at 6.4–8.2 times greater frequency in HD than in non-HD brains (discovery cohort: OR 8.68, 95% CI 3.48–21.63, P=4.8 × 10-5; validation cohort: OR 6.50, 95% CI 1.83–23.17, P=0.0050). Periventricular nodular heterotopias (PNH) were the most frequent malformations and contained HTT and p62 aggregates analogous to the cortex, whereas cortical malformations with immature neuronal populations did not harbor such inclusions. HD individuals with malformations had heterozygous HTT CAG expansions between 40 and 52 repeats, were more frequently women, and all were asymmetric and focal, aside from one midline hypothalamic hamartoma. Using two independent brain bank cohorts, this large neuropathologic series demonstrates an increased occurrence of developmental malformations in HD brains. Since pathogenic HTT gene expansion is associated with genomic instability, one possible explanation is that neuronal precursors are more susceptible to somatic mutation of genes involved in cortical migration. Our findings further support emerging evidence that pathogenic trinucleotide repeat expansions of the HTT gene may impact neurodevelopment.

EFFICACY AND SENSITIVITY OF PRENATAL AND POSTNATAL ULTRASOUND SCREENING OF CONGENITAL DEVELOPMENTAL ANOMALIES OF KIDNEYS IN SLOVAKIA

The aim: To compare the effectiveness and sensitivity of prenatal and postnatal diagnostics in the diagnosis of congenital malformations of the urinary system in the Slovak Republic. Materials and methods: Data of postnatal sonographic screening of congenital developmental malformations of the urinary system in Slovak Republic including 2017 were identified and updated using a questionnaire survey, 38,496 newborns were involved. Statistical data on the proportion of prenatal diagnosis for the years 1995, 2000, 2005, 2008 and 2013-2016 were provided from the National Register of Congenital Defects. The chi2-test and t-test were applied to assess the sensitivity differences. Results: The study showed a low sensitivity of prenatal diagnosis with its maximum in 2016, reaching 32.3% and a minimum in 2005-2008 (8.0 – 8.4%). The sensitivity of postnatal diagnostics for selected years has always been a stable indicator and reaches 99.6%. Conclusions: Available statistical data confirm that prenatal diagnostics of congenital developmental malformations of the urinary system in the Slovak Republic is not perfect. Our work underlines the importance, or we should rather say inevitability of postnatal ultrasound screening for congenital developmental anomalies in the kidneys.

Intraoral Foregut Cystic Developmental Malformations: Three cases with a brief review of literature

Foregut cystic developmental malformations (FCDM) are a type of rare cystic lesion. The occurrence of FCDM is exceedingly uncommon in the intraoral location. We report three cases of FCDM with intraoral location who presented at Chacha Nehru Bal Chikitsalaya, New Delhi, India, in 2016, 2017 and 2018 with symptoms of respiratory distress and feeding difficulties. Two patients were male and one was female with an age range of 29 days to eight years. The clinical differential diagnosis included mucocele, ranula, dermoid, lymphangioma, teratoma, thyroglossal duct cyst, etc. All patients were treated with simple surgical excision and diagnosed, based on histopathology, with FCDM. These should be considered as differential diagnosis of head and neck midline cystic mass lesions. This case report aimed to discuss differential diagnosis and appropriate terminology for these cystic masses as there is varied and ambiguous nomenclature.Keywords: Bronchogenic Cyst; Cyst; Congenital Abnormalities; Oral Cavity; Case Report; India.