Complex de novo chromosomal rearrangement at 15q11-q13 involving an intrachromosomal triplication in a patient with a severe neuropsychological phenotype: clinical report and review of the literature.

Interstitial triplications of 15q11-q13, leading to tetrasomy of the involved region, are very rare, with only 11 cases reported to date. Their pathogenicity is independent of the parental origin of the rearranged chromosome. The associated phenotype resembles, but is less severe, than that of patients bearing inv dup(15) marker chromosomes. Here, we describe a boy of 3 years and 9 months of age who exhibited very mild craniofacial dysmorphism (arched eyebrows, hypertelorism, and a wide mouth), developmental delay, generalized hypotonia, ataxic gait, severe intellectual disability, and autism. Array comparative genomic hybridization (CGH) analysis identified a heterozygous duplication of 1.1 Mb at 15q11.2 (between low-copy repeats BP1 and BP2), and a heterozygous triplication of 6.8 Mb at 15q11.2-q13.1 (BP2-BP4). Both acquisitions were de novo and contiguous. Microsatellite polymorphism analysis revealed the maternal origin of the triplication and the involvement of both maternal chromosomes 15. Furthermore, fluorescence in situ hybridization (FISH) analysis using BAC clones revealed that the rearrangement was complex, containing three differently sized tandem repeats of which the middle one was inverted. Our study confirms and extends the model proposed to explain the formation of intrachromosomal triplications through recombination events between non-allelic duplicons. The comparison of the proband's clinical presentation with those of previously described cases attests the existence of endophenotypes due to the parental origin of the 15q11-q13 triplicated segment and suggests a timetable for achievement of developmental milestones, thereby contributing to improved genotype-phenotype correlations.

Adolescent migraine: diagnostic and therapeutic approaches.

Migraine prevalence increases from infancy to adolescence thus suggesting the important role of adolescent somatic and emotional maturation in supporting the disease. New family and society relationship and scholastic experiences represent more or less stress moments, producing risk factors for adolescent migraine. There are few studies adequately assessing migraine treatment efficacy in adolescent attack and prevention. Adolescent migraine's treatment with pharmacological and nonpharmacological therapies needs an individualized approach considering adolescent development degree, risk factors and trigger circumstances, psychological correlates and even psychiatric or other comorbidities.

Improvement in diagnostic-therapeutic care pathways for women with migraine: an Italian Delphi panel.

Background: Migraine is a highly underestimated and burdensome disease. Real-world studies evidence that migraine is more frequent and severe in women than men. However, to this day, no diagnostic-therapeutic pathways exist to satisfy the specific needs of female patients. Methods: In this study, migraine experts, specialists in women's health, patient, and decision makers, analyzed the diagnostic and therapeutic options for women with migraine across various ages and health conditions within the Italian healthcare system. A Delphi approach was used to formulate statements and achieve a consensus. Results: Gaps in clinical practice were identified, and strategies to accommodate women's needs were proposed. The experts agreed that a socio-behavioral intervention should be planned before any pharmacological treatment in pediatric/adolescent female patients and that the assessment of migraine with aura is considered crucial for adult women requiring contraceptive therapy. Acupuncture emerged as an effective treatment for pregnant and breastfeeding women, and hormone-replacement therapy selection in menopausal patients requires careful consideration to mitigate safety risks. The experts highlighted the absence of literature and guidelines for the management of migraine in women undergoing assisted reproductive procedures or oncological treatment. In light of these observations, the experts advocated the establishment of multidisciplinary collaborations between neurologists/headache specialists and other healthcare professionals, including general practitioners, pediatricians, gynecologists, and oncologists. Comprehensive migraine education for all healthcare professionals potentially involved in managing the disease, including pharmacists, was emphasized. Efforts to increase migraine awareness among women should be prioritized. Conclusion: The insights gained from this Italian consensus study should serve to develop an improved, female-specific pathway to diagnose and treat migraine.

Osmophobia as an early marker of migraine: a follow-up study in juvenile patients.

BACKGROUND: Osmophobia is frequent in children with migraine (20-35%) but can also occur in up to 14% of cases with tension-type headache (TTH). So far, the prognostic role of this symptom in children with primary headaches has never been evaluated. METHODS: A longitudinal prospective study was conducted on 90 young patients with TTH (37 with osmophobia, 53 without osmophobia). We evaluated whether osmophobia could predict the diagnosis transformation from TTH to migraine after a 3-year follow-up. RESULTS AND DISCUSSION: In our cases the rate of diagnosis change was significantly greater in cases with osmophobia (62%) than in those without (23%). Osmophobia persisted at a 3-year follow-up in the majority of our cases (85%) and it was found to be one of the major predictors for the development of migraine; other predictors of evolution to migraine were phonophobia, a probable rather than certain diagnosis of TTH and olfactory triggers (p < 0.05). CONCLUSION: Our data confirm that osmophobia has an important diagnostic and prognostic role in children with primary headaches and should be systematically investigated at diagnosis and during follow-up.

Parry-Romberg syndrome: conventional and advanced MRI follow-up in a boy.

We studied a 9-year-old boy, affected with the Parry-Romberg syndrome, during a period of 32 months, by means of clinical evaluations and neuroradiological magnetic resonance imaging. Over this time we observed a clinical progression of the cutaneous disease without a simultaneous progression of the neurological alterations. Conventional and advanced magnetic resonance imaging techniques showed white matter alterations which proved to be stable during the follow-up.