A prenatal presentation of severe microcephaly and brain anomalies in a patient with novel compound heterozygous mutations in the STIL gene found postnatally with exome analysis.

OBJECTIVE: This report outlines how current fetal neuroimaging and genomic technologies can aid in determining the causes of prenatal microcephaly. BACKGROUND: The differential diagnosis and prognosis of fetal microcephaly is a challenging and common presenting problem to the child neurologist and perinatologist. There was a time that the prospective parents could only be told that the child would be microcephalic. Not much could be determined in regard to exact diagnosis or prognosis. METHODS: At 20 weeks' gestation the fetus was observed to have isolated microcephaly on fetal ultrasound. Karyotyping and a nontargeted genomic microarray were performed at 21&4/7 weeks gestation on amniocytes and the results were normal. At this time, toxoplasmosis, rubella, syphilis, cytomegalovirus and herpes studies were also negative. Fetal magnetic resonance imaging at 31 weeks' gestation revealed severe microcephaly with an anomaly consistent with holoprosencephaly. Whole-exome sequence analysis was performed. RESULTS: Postnatal whole-exome sequence analysis revealed two novel compound heterozygous mutations in the STIL gene (c.2354_2355dupGA and c.3835C>T), which is consistent with microcephaly and migrational anomalies. The postnatal magnetic resonance imaging reveals agenesis of the corpus callosum, agyria of the frontal and temporal lobes, and a large cyst along the interhemispheral fissure extending to the parietal and occipital regions in addition to pontine and cerebellar dysgenesis. CONCLUSION: This case demonstrates the state-of-the-art approach to the clinical challenge of prenatal microcephaly and defines unique findings associated with compound heterozygous STIL gene mutations c.2354_2355dupGA and c.3835C>T.

Allergic rhinitis in children with attention-deficit/hyperactivity disorder.

BACKGROUND: Both allergic rhinitis and attention-deficit/hyperactivity disorder (ADHD) are common pediatric conditions associated with learning difficulties and sleep disturbances. There are conflicting research data regarding the association between ADHD and atopic disorders. OBJECTIVE: To determine the prevalence of allergic rhinitis in patients with physician-diagnosed ADHD. METHODS: Patients 5 to 18 years of age who presented with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of ADHD to an outpatient pediatric psychiatry clinic were screened for allergic rhinitis with focused history, physical examination, and skin prick testing to common aeroallergens. RESULTS: Thirty patients were interviewed, with 23 of these undergoing physical examination and skin prick testing. Eighty percent reported allergic rhinitis symptoms, whereas 61% had at least 1 positive prick skin test result. Forty-three percent showed typical physical signs of allergic rhinitis, 100% had a positive atopic family history, and 53% had other associated atopic disorders. CONCLUSIONS: Most children with ADHD displayed symptoms and skin prick test results consistent with allergic rhinitis. Nasal obstruction and other symptoms of allergic rhinitis could explain some of the cognitive patterns observed in ADHD, which might result from sleep disturbance known to occur with allergic rhinitis. Therefore, evaluation and treatment of allergic rhinitis could benefit patients with ADHD.