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Abstract Background Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome, also referred to as Müllerian aplasia, is a congenital disorder characterized by aplasia of the uterus and upper part of the vagina in females with normal secondary sex characteristics and a normal female karyotype (46,XX). Main body The diagnosis is often made during adolescence following investigations for primary amenorrhea and has an estimated prevalence of 1 in 5000 live female births. MRKH syndrome is classified as type I (isolated uterovaginal aplasia) or type II (associated with extragenital manifestations). Extragenital anomalies typically include renal, skeletal, ear, or cardiac malformations. The etiology of MRKH syndrome still remains elusive, however increasing reports of familial clustering point towards genetic causes and the use of various genomic techniques has allowed the identification of promising recurrent genetic abnormalities in some patients. The psychosexual impact of having MRKH syndrome should not be underestimated and the clinical care foremost involves thorough counselling and support in careful dialogue with the patient. Vaginal agenesis therapy is available for mature patients following therapeutical counselling and education with non-invasive vaginal dilations recommended as first-line therapy or by surgery. MRKH syndrome involves absolute uterine factor infertility and until recently, the only option for the patients to achieve biological motherhood was through gestational surrogacy, which is prohibited in most countries. However, the successful clinical trial of uterus transplantation (UTx) by a Swedish team followed by the first live-birth in September, 2014 in Gothenburg, proofed the first available fertility treatment in MRKH syndrome and UTx is now being performed in other countries around the world allowing women with MRKH syndrome to carry their own child and achieve biological motherhood. Conclusion Several advances in research across multiple disciplines have been made in the recent years and this kaleidoscopic review provides a current status of various key aspects in MRKH syndrome and provides perspectives for future research and improved clinical care.

Abstract Background Doyne honeycomb retinal dystrophy (DHRD)/malattia leventinese (ML) is an autosomal dominant, progressive retinal disorder characterized by massive central retinal drusen often partly coalescent forming a characteristic honeycomb‐like pattern. Debut of vision loss often occurs in early to mid‐adulthood, and the degree varies. A single variant in EFEMP1: c.1033C>T (R345W) has been identified as the cause in all cases. Methods Following DNA isolation, exome sequencing was performed in seven genes associated with flecked retina. Direct sequencing was used for variant verification. Results We report the first Scandinavian case of molecular genetically verified DHRD/ML: a 57‐year‐old woman debuting with vision loss and metamorphopsia. On both eyes, ophthalmological findings included massive hard drusen in the macular region and nasal to the optic disc as well as macular hyperpigmentation. Secondary choroidal neovascularizations were identified on both eyes, and anti‐vascular endothelial growth factor was administered, without effect. Conclusion Molecular genetic investigation revealed heterozygosity for the known pathogenic missense variant in EFEMP1: c.1033C>T (R345W) previously reported in relation to DHRD/ML. Family history revealed no other cases of similar visual impairment suggesting a de novo mutation. Furthermore, there was no correlation between the unique DHRD/ML haplotypes reported in the literature and our patient.

Abstract Background CABP2‐related non‐syndromic hearing loss have only been reported in a few families worldwide (Iran, Turkey, Pakistan and Italy). The hearing loss was in these cases described as prelingual, symmetrical, and moderate to severe. Methods Following DNA isolation, exome sequencing was performed in 123 genes related to non‐syndromic hearing loss. Variant verification and carrier testing were performed by direct sequencing. Results We report the first Northern European individual with CABP2‐related hearing loss: an 8‐year‐old Danish Caucasian boy with non‐syndromic, prelingual, and sensorineural hearing loss, who is homozygous for the splice site variant CABP2: c. 637+1G>T previously found in three Iranian families and in one Pakistani family. Both parents are of Danish Caucasian origin with no known history of consanguinity. This is in contrast to the four reported Middle Eastern families, who all were consanguineous. However, loss of heterozygosity in a 3.2 Mb area on chromosome 11 including CABP2 was observed, suggesting a common parental ancestor. Conclusion We report the first case of CABP2‐related autosomal recessive hearing loss in Northern Europe. The index is of Danish Caucasian origin and found to be homozygous for the splice site variant c.637+1G>T.