Homozygous missense variants in BMPR15 can result in primary ovarian insufficiency.

RESEARCH QUESTION: Does a genetic condition underlie the diagnosis of primary ovarian insufficiency (POI) in a 13-year-old girl with primary amenorrhoea? DESIGN: A case report of a next-generation sequencing panel of 24 genes associated with syndromal and non-syndromal POI was conducted. RESULTS: A homozygous missense variant c.1076C>T, p.(Pro359Leu) in BMP15 was identified. CONCLUSIONS: The biallelic variant c.1076C >T, p.(Pro359Leu) in BMP15 is associated with primary ovarian failure.

Ligase IV syndrome can present with microcephaly and radial ray anomalies similar to Fanconi anaemia plus fatal kidney malformations.

Ligase IV (LIG4) syndrome is a rare disorder of DNA damage repair caused by biallelic, pathogenic variants in LIG4. This is a phenotypically heterogeneous condition with clinical presentation varying from lymphoreticular malignancies in developmentally normal individuals to significant microcephaly, primordial dwarfism, radiation hypersensitivity, severe combined immunodeficiency and early mortality. Renal defects have only rarely been described as part of the ligase IV disease spectrum. We identified a consanguineous family where three siblings presenting with antenatal growth retardation, microcephaly, severe renal anomalies and skeletal abnormalities, including radial ray defects. Autozygosity mapping and exome sequencing identified a novel homozygous frameshift variant in LIG4, c.597_600delTCAG, p.(Gln200LysfsTer33), which segregated in the family. LIG4 is encoded by a single exon and so this frameshift variant is predicted to result in a protein truncated by 678 amino acids. This is the shortest predicted LIG4 protein product reported and correlates with the most severe clinical phenotype described to date. We note the clinical overlap with Fanconi anemia and suggest that LIG4 syndrome is considered in the differential diagnosis of this severe developmental disorder.

Vulvar swelling as the first presentation of Crohn's disease in children-A report of three cases.

Vulvar swelling is a rare manifestation of metastatic Crohn's disease in children. It often predates gastrointestinal symptoms and can be the first presentation of pediatric Crohn's disease. We report three cases of pediatric Crohn's disease presenting with vulvar swelling. We discuss this rare presentation and its treatment and highlight the importance of recognizing it so that prompt investigation and appropriate management can be initiated.

Outcomes of women referred for sterilisation.

OBJECTIVE: To evaluate whether women referred to a gynaecology clinic requesting sterilisation were receiving appropriate counselling about sterilisation and other forms of long-term contraception, and to determine the proportion of women who ultimately underwent sterilisation. METHODS: A retrospective audit of 100 women referred requesting sterilisation. RESULTS: 15% of women referred did not attend the clinic, 54% had sterilisation and 29% ultimately chose an alternative method. Alternative forms of contraception discussed were levonorgestrel-releasing intrauterine system (69%), vasectomy (34%) and subdermal progestogen implants (21%). At the clinic 70 (82%) women chose sterilisation; however, 15 (21%) of these women cancelled the operation. CONCLUSIONS: Almost half of the women referred for sterilisation did not proceed with it, suggesting that there was insufficient counselling about sterilisation and alternative long-term contraception before referral to the gynaecology clinic and also within the clinic itself.