Contrary to our initial hypothesis, tea ingestion caused larger acute increases in blood pressure than caffeine alone. However, any acute effects of tea on blood pressure did not translate into significant alterations in ambulatory blood pressure during regular tea consumption.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a progressive, generally late-onset, neurological disorder associated with biallelic pentanucleotide expansions in intron 2 of the RFC1 gene. The locus exhibits substantial genetic variability, with multiple pathogenic and benign pentanucleotide repeat alleles previously identified. To determine the contribution of pathogenic RFC1 expansions to neurological disease within an Australasian cohort and further investigate the heterogeneity exhibited at the locus, a combination of flanking and repeat-primed PCR was used to screen a cohort of 242 Australasian neurological disease patients. Patients whose data indicated large gaps within expanded alleles following repeat-primed PCR, underwent targeted long-read sequencing to identify novel repeat motifs at the locus. To increase diagnostic yield, additional probes at the RFC1 repeat region were incorporated into the PathWest diagnostic laboratory targeted neurological disease gene panel to enable first pass screening of the locus for all samples tested on the panel. Within the Australasian cohort, we detected known pathogenic biallelic expansions in 15.3% (n = 37) of cases. Thirty indicated biallelic AAGGG expansions, two had biallelic Māori alleles [(AAAGG)exp(AAGGG)exp], two samples were compound heterozygous for the Māori allele and a AAGGG expansion, two samples had biallelic ACAGG expansions and one sample was compound heterozygous for the ACAGG expansion and the AAGGG expansion. Forty-five samples tested indicated the presence of biallelic expansions not known to be pathogenic. A large proportion (84%) showed complex interrupted patterns following repeat-primed PCR, suggesting that these expansions are likely to be comprised of more than one repeat motif including previously unknown repeats. Using targeted long-read sequencing we identified three novel repeat motifs in expanded alleles. Here we also show that short read sequencing can be used to reliably screen for the presence or absence of biallelic RFC1 expansions in all samples tested using the PathWest targeted neurological disease gene panel. Our results show that RFC1 pathogenic expansions make a substantial contribution to neurological disease in the Australasian population and further extend the heterogeneity of the locus. To accommodate the increased complexity, we outline a multi-step workflow utilising both targeted short- and long-read sequencing to achieve a definitive genotype and provide accurate diagnoses for patients.

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The neurocutaneous syndromes comprise a diverse group of rare genetic disorders with both neurological and cutaneous manifestations. Each syndrome has a distinct phenotype. Symptoms are variable and depend on the syndrome. Neurocutaneous syndromes often present in childhood or adolescence; for example, tuberous sclerosis typically presents in early childhood. The age range of presentation is broad, depending on the specific condition and severity of expression. The majority are autosomally inherited conditions. De novo mutations can occur. Most neurocutaneous syndromes do not have a specific treatment, and management is predominantly supportive and aimed at symptom reduction and appropriate monitoring. This chapter discusses neurocutaneous syndromes, including their symptoms, demographics, etiologies, natural history, complications, diagnosis, prognosis, and treatment.