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Objective: The incidence of congenital hypothyroidism (CHT) has progressively increased in several regions around the world but has yet to be evaluated in Northern Ireland (NI). CHT screening programme was introduced in NI in 1980 and has had a relatively unchanged protocol since its inception. The purpose of the study was to evaluate the incidence of CHT in NI from 1981 to 2020 and to explore possible contributing factors to any changes seen over the 40-year period., Design: This was a retrospective database review of children diagnosed with CHT in NI between 1981 and 2020. Data was collected from the patients' medical (paper and electronic) records, including epidemiological, clinical, laboratory, and radiological features as well as outcomes at 3 years., Results: Of 800,404 new-borns who were screened for CHT in NI between January 1981 and March 2020, 471 were diagnosed with CHT. There was a steady and significant increase in incidence of CHT over time with an incidence of 26 cases per 100,000 livebirths in 1981 versus 71 cases per 100,000 in 2019 (p < .001). Of these 471, 77 new-borns (16%) were born preterm. The incidence of CHT was observed twice as much in female compared to male new-borns. Diagnostic imaging including radioisotope uptake and thyroid ultrasound scans were performed in 143 cases (30%). Of these, 101 (70%) cases had thyroid dysgenesis and 42 (30%) cases had thyroid dyshormonogenesis. There were 293 (62%) of 471 patients had confirmed permanent CHT, and 90 patients (19%) had transient CHT. Over that period at least 95% of the population were recorded as having United Kingdom/Ireland as country of birth., Conclusion: Our findings demonstrate a nearly tripling of the CHT incidence observed over the last 40 years. This is against a background of a relatively stable population demographics. Future research should focus on the underlying cause(s) of this condition which may include changing environmental exposures in utero., (© 2023 John Wiley & Sons Ltd.)

Background: Iodine deficiency has re-emerged among pregnant cohorts in the UK. Thyroglobulin (Tg) is a protein produced uniquely by the thyroid gland which appears to mount a U-shaped response to extremes of iodine status. Tg has been suggested as an alternative marker for chronic iodine deficiency but the value of Tg in pregnancy has not been fully elucidated. A recent non-European study suggested a median Tg ≤10 µg/L with &lt;3% of values &gt;44 µg/L was indicative of sufficiency in the second trimester of pregnancy., Methods: We measured serum Tg levels in each trimester in 241 pregnant women living in Northern Ireland, a population with mild iodine deficiency at all stages of pregnancy as defined by urinary iodine concentration (UIC) and iodine: creatinine ratio (ICR). Women with Tg antibodies (6% in 1st trimester) were excluded., Results: The median UIC in this cohort was in the deficient range at 73, 94 and 117 µg/L in sequential trimesters (adequacy ≥ 150 µg/L). Corresponding median Tg levels were 19, 16 and 16 µg/L respectively. Median Tg for all samples was 17 μg/L (IQR 11-31) suggestive of iodine deficiency. Tg was &gt;44 μg/L in 14.3%, 9.4% and 12.4% of women in sequential trimesters respectively. Women with either UIC/ICR below the cut-offs 150 µg/L and 150 µg/g creatinine had higher Tg concentrations in 1st and 2nd trimester (p &lt; 0.01; p &lt; 0.001) but not in 3rd trimester., Conclusion: This study adds to the evolving evidence that Tg measurement is of value in reflecting iodine status in pregnancy., (© 2022. The Author(s).)

Iodine is required for thyroid hormone synthesis and fetal neurogenesis. Recent population studies in the United Kingdom (UK) have found iodine deficiency among schoolgirls, women of child-bearing age and pregnant women. This review explores knowledge and awareness of iodine among women of child-bearing age and healthcare professionals (HCPs) in the UK, set within a global context. We aimed to identify gaps in iodine knowledge in the current UK setting of iodine deficiency without iodine fortification and where iodine is not included in antenatal guidelines. The search terms 'iodine knowledge' and 'iodine awareness' were used to identify relevant papers. Iodine knowledge is poor among women of child-bearing age in the UK according to four studies using questionnaires and qualitative methods. They were unsure of dietary sources of iodine and were not consistently provided with relevant information from HCPs during clinical care. Midwives have been recognised as the main providers of dietary information during pregnancy and, although they recognised the importance of their role in providing nutrition advice, they did not feel equipped to do so and lacked confidence in addressing nutritional concerns. Globally, there was a similar lack of knowledge, however, this was somewhat improved by the inclusion of iodine in antenatal care guidelines. Midwives' knowledge of iodine was poor, as was knowledge among women of child-bearing age. Improved HCP knowledge and effective communication of information to pregnant women and women planning to conceive may help to improve iodine status which is of particular concern in pregnancy., (© The Author(s) 2022.)

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by marked variation in clinical severity. To investigate the contribution to variability by genes either contiguous to or contained within the NF1 gene, we screened six NF1 patients with mild facial dysmorphology, mental retardation, and/or learning disabilities, for DNA rearrangement of the NF1 region. Five of the six patients had NF1 gene deletions on the basis of quantitative densitometry, locus hemizygosity, and analysis of somatic cell hybrid lines. Analyses of hybrid lines carrying each of the patient's chromosomes 17, with 15 regional DNA markers, demonstrated that each of the five patients carried a deletion > 700 kb in size. Minimally, each of the deletions involved the entire 350-kb NF1 gene; the three genes--EVI2A, EVI2B, and OMG--that are contained within an NF1 intron; and considerable flanking DNA. For four of the patients, the deletions mapped to the same interval; the deletion in the fifth patient was larger, extending farther in both directions. The remaining NF1 allele presumably produced functional neurofibromin; no gene rearrangements were detected, and RNA-PCR demonstrated that it was transcribed. These data provide compelling evidence that the NF1 disorder results from haploid insufficiency of neurofibromin. Of the three documented de novo deletion cases, two involved the paternal NF1 allele and one the maternal allele. The parental origin of the single remaining expressed NF1 allele had no dramatic effect on patient phenotype. The deletion patients exhibited a variable number of physical anomalies that were not correlated with the extent of their deletion. All five patients with deletions were remarkable for exhibiting a large number of neurofibromas for their age, suggesting that deletion of an unknown gene in the NF1 region may affect tumor initiation or development.

Recently the M17S1 gene, encoding an epidermal antigen thought to play a role in cell adhesion, was mapped to chromosome bands 17q11-q12, placing it in the vicinity of the gene for the genetic disorder neurofibromatosis 1 (NF1). The pleomorphic cutaneous lesions of NF1 and the precedent for other genes being embedded within the NF1 gene prompted us to investigate whether the M17S1 gene mapped near, or within, the NF1 gene. Genetic linkage analyses revealed that M17S1 was tightly linked to NF1 and mapped within the interval bounded by D17S58 and D17S54. Physical mapping of an M17S1 cDNA on somatic cell hybrids, yeast artificial chromosomes, and an NF1 patient with a deletion involving an entire NF1 allele demonstrated that M17S1 is located at least 180 kb centromeric to the NF1 gene. The distance between the genes suggests that M17S1 is unlikely to contribute to the NF1 phenotype since a gross chromosomal rearrangement would be required to disrupt expression of both genes.

An interesting feature of neurofibromatosis type 1 (NF1) is its high mutation rate of 1 x 10(-4) per gamete per generation. The molecular basis for frequent NF1 mutation in unknown; the gene is not deletion prone. We have found that in all ten families examined, the apparent new NF1 mutation occurred on the paternally-derived chromosome. The probability of observing this result by chance is less than 0.001 assuming an equal frequency of mutation of paternal and maternal NF1 genes. We hypothesize a role for genomic imprinting that may either enhance mutation of the paternal NF1 gene or confer protection from mutation to the maternal NF1 gene.