BACKGROUND: Hypohidrotic ectodermal dysplasia (HED) is a genetic disorder that results in the abnormal development of structures derived from ectodermal tissue. This rare condition predominantly affects the hair, nails, eccrine glands, and teeth. While HED can be caused by various genes, the EDA, EDAR, EDARADD, and WNT10A genes account for approximately 90% of cases. Notably, HED forms associated with variants in the EDA, EDAR, or EDARADD genes may exhibit similar phenotypes due to defects in a common signaling pathway. Proper interaction among the products of these genes is crucial for the activation of the nuclear factor (NF-κB) signaling pathway, which subsequently regulates the transcription of targeted genes. The EDARADD gene, in particular, harbors one of the rarest reported variants associated with HED.
METHODS: Five-and two-years-old brothers born into consanguineous parents were examined at our outpatient medical genetics clinic at Sanliurfa Training and Research Hospital, Turkey. Both displayed the same classical phenotypic features of HED. The elder had a very sparse dark and brittle hair, sparse eyebrows and eyelashes, conical upper and lower premolar teeth with hypodontia, widely spaced teeth, very dry skin, mildly prominent forehead, and periorbital wrinkles. The younger one showed the same, but less severe, clinical features. After thorough examination and patient history evaluation, targeted next-generation sequencing analysis yielded the novel homozygous insertion variant c.322_323insCGGGC p.(Arg108ProfsTer7) in EDARADD. The mutation has not been reported to date in the literature.
CONCLUSIONS: In this report, we present two siblings exhibiting classical HED symptoms and a novel insertion variant of the EDARADD gene, which leads to a frameshift introducing a stop codon. Both brothers inherited such mutation from their parents, who were heterozygous carriers of the same variant. The present study may shed light about the pathogenic mechanisms underlying HED, and expand the spectrum of EDARADD gene variants associated with this condition.

The pectoralis minor (PMn) muscle originates from the third, fourth, and fifth ribs near the costochondral junctionusually and gets inserted on the medial margin and upper surface of the coracoid process of the scapula. To look at the morphological insertion patterns and sites of attachment of the PMn muscle in the donated cadavers. Over all 19 limbs were included in the study (9 right and 10 left). Out of 19 limbs, 10 belonged to female and 9 belonged to male cadavers. The cadavers were meticulously dissected to determine the morphological insertion types and location of the attachment of the muscle. Unusual pattern of insertion was observed in 6 limbs (31.6%) out of total 19 limbs included in the study. The variations we observed does not fall completely in the classification by Le Double, hence variations we observed can be considered as new and rare variant which to our knowledge is not reported in literature. We propose this new variant to be type 4 of Le Double classification. The potential of ectopic PMn tendon should be taken into consideration and tested out, especially in patients with shoulder discomfort and stiffening who have ruled out the more frequent diseases. For proper surgical planning, a preoperative magnetic resonance imaging or USG examination of the shoulder joint is required considering the prevalence of variation in the insertion pattern of PMn muscle. Preoperative identification of any abnormal PMn insertion can help to reduce the risk of iatrogenic tendon injury and post-operative problems.

Intrachromosomal amplification of RUNX1 gene on chromosome 21 (iAMP21) is a rare occurrence in acute myeloid leukemia (AML). Herein, we describe a case of AML with amplification of RUNX1 and its insertion on chromosome 2 detected by conventional karyotyping and confirmed by metaphase FISH. A six-year-old female was diagnosed as acute myeloid leukemia with monocytic differentiation. The patient\'s bone marrow revealed 74% blasts which were MPO negative. Conventional karyotyping revealed a complex karyotype, with rearrangements in chromosomes 1, 2, 7, 8 and hsr(21). FISH on interphase cells with LSI RUNX1-RUNX1T1 dual colour dual fusion translocation probe showed 6-7 copies of RUNX1 signal. Metaphase FISH with LSI RUNX1-RUNX1T1 probe confirmed amplification of RUNX1 and insertion of amplified RUNX1 sequences on long arm of chromosome 2. Induction chemotherapy was initiated, however, the patient died within one month of diagnosis suggesting poor outcome associated with this novel finding. Insertion of amplified RUNX1 on another chromosome has not yet been reported so far.

Infertility is an important health problem affecting 15% of couples worldwide. Intellectual disability (ID) is characterized with significant impairment of intellectual function, adaptive daily life skills and social skills. Insertion is a rare chromosomal rearrangement causing infertility and ID. Here, we report a 39-year-old man presenting with primary infertility and mild ID. The patient\'s spermiogram was consistent with azoospermia. Conventional cytogenetic analysis showed a novel inversion/insertion type of chromosomal aberration involving chromosomes 18 and 2: 46, XY, inv ins(18;2)(q11.2;q13q22). We carried out the array comparative genomic hybridization analysis to confirm the cytogenetic findings. Y micro-deletion analysis demonstrated that the AZF region as intact. We suggest that the novel insertion found in this case [46, XY, inv ins(18;2)(q11.2;q13q22)] may have caused infertility and mild ID in our patient. To the best of our knowledge, this chromosomal insertion has not previously been reported.

Aberrant insertions of the pectoralis minor tendon are quite rare. Most cases are incidental findings during cadaver dissections, on an MRI or during surgical procedures of the shoulder joint. Rarely the aberrant insertion points can be a source of pain or restriction of the shoulder joint. From the literature review, we found that there has been no mention regarding the frequency of occurrence of this variation with respect to unilateral or bilateral occurence, and only three cases have been reported, in which aberrant bilateral insertions have been documented of which two were noted during cadaveric dissection and one radiologically. We report a rare case of aberrant bilateral insertions of the pectoralis minor, which was found during an arthroscopic procedure, and we discuss its clinical and surgical implications.

Hypertrophic cardiomyopathy (HCM) is a cardiovascular disease with autosomal dominant inheritance caused by mutations in genes coding for sarcomeric and/or regulatory proteins expressed in cardiomyocytes. In a small cohort of HCM patients (n=8), we searched for mutations in the two most common genes responsible for HCM and found four missense mutations in the MYH7 gene encoding cardiac β-myosin heavy chain (R204H, M493V, R719W, and R870H) and three mutations in the myosin-binding protein C3 gene (MYBPC3) including one missense (A848V) and two frameshift mutations (c.3713delTG and c.702ins26bp). The c.702ins26bp insertion resulted from the duplication of a 26-bp fragment in a 54-year-old female HCM patient presenting with clinical signs of heart failure due to diastolic dysfunction. Although such large duplications (>10 bp) in the MYBPC3 gene are very rare and have been identified only in 4 families reported so far, the identical duplication mutation was found earlier in a Dutch patient, demonstrating that it may constitute a hitherto unknown founder mutation in central European populations. This observation underscores the significance of insertions into the coding sequence of the MYBPC3 gene for the development and pathogenesis of HCM.

Presented is the first reported case of an anaphylactoid reaction following Norplant contraceptive implant insertion. The 19-year-old UK woman denied any history of allergic reaction to local anesthesia. After subcutaneous infiltration with 50 mg of 1% lidocaine (without adrenalin), 6 Norplant capsules were inserted through use of the standard insertion technique. Shortly after completion of the procedure, the patient collapsed and had 2 short convulsions. Her blood pressure dropped to 80/40 mm Hg and her radial pulse was 60 beats/minute and thready. Recovery was rapid following administration of intramuscular adrenalin and intravenous hydrocortisone. The woman later recalled a similar episode during a visit to her dentist. An estimated 3 in every 100,000 patients receiving lignocaine hydrochloride have an episode of anaphylaxis in the hospital. In type I hypersensitivity reactions, there is often a history of previous exposure to the allergen, as occurred in this patient. Those undertaking Norplant insertion and removal should be aware of the potential for serious allergic reactions and have access to resuscitative equipment.

To delineate characteristics of women predisposing to sterilization technical failures, we performed an analysis of 20 technical failures that occurred during tubal ring procedures and 80 control ring procedures matched on planned surgical approach and study site. None of the women had recently been pregnant (interval procedures). The odds ratios (ORs) were elevated for women wearing an IUD in the three months prior to sterilization (OR = 5.0, 90% confidence interval [CI] 2.2, 11.2) and for women with a history of spontaneous abortion (OR = 4.3, 90% CI 1.8, 9.8). A history of pelvic inflammatory disease (PID) and/or current evidence of PID was strongly associated with technical failure (X2 = 25.0, p less than 0.001). The combined effect of any two of these three factors increased the risk synergistically. We examined these factors prospectively and confirmed the elevated risks (relative risk [RR] = 5.0, 5.5 and 22.7 for recent IUD wearing, spontaneous abortion history and history/evidence of PID, respectively). The prospective analysis also found that previous abdominal surgery is associated with technical failure (RR = 6.7).
To delineate characteristics of women predisposing to sterilization technical failures, we performed an analysis of 20 technical failures that occurred during tubal ring procedures and 80 control ring procedures matched on planned surgical approach and study site. None of the women had recently been pregnant (interval procedures). The odds ratios (ORs) were elevated for women wearing an IUD in the 3 months prior to sterilization (OR=5.0, 90% confidence interval CI 2.2, 11.2) and for women with a history of spontaneous abortion (OR=4.3, CI 1.8, 9.8). A history of pelvic inflammatory disease (PID) and/or current evidence of PID was strongly associated with technical failure (X squared=25.0, p less than 0.001). The combined effect of any 2 of these 3 factors increased the risk synergistically. We examined these factors prospectively and confirmed the elevated risks (relative risk RR =5.0, 5.5 and 22.7 for recent IUD wearing, spontaneous abortion history and history/evidence of PID, respectively). The prospective analysis also found that previous abdominal surgery is associated with technical failure (RR=6.7).

This investigation, using a case-control analysis approach on an IUD data set from a less-developed country center, delineated four risk factors in patient characteristics that are associated with severe pain at interval IUD insertion. They are: higher education (greater than or equal to seven years), low-parity (1-2 live births), longer open interval (greater than or equal to 13 months) between the end of the last pregnancy and insertion, and non-breastfeeding at the time of insertion. Adjusted relative risks estimated by odds ratios are 2.1, 2.7, 2.7 and 5.0, respectively. For women with a combination of the above risk factors, they have a further increased (additive in nature) risk of suffering severe insertion pain. Similar analysis was also performed on a developed country center data set for which only the effect of education and parity could be studied; an odds ratio of 5.0 for nulliparity was obtained. The plausibility of these findings as well as their clinical and programmatic implications are discussed.
This investigation, using a case-control analysis approach on an intrauterine device (IUD) data set from a less-developed country center, delineated 4 risk factors in patient characteristics that are associated with severe pain at interval IUD insertion. They are: higher education ( or = 7 years) low parity (1-2 live births), longer open interval ( or = 13 months) between the end of the last pregnancy and insertion, and non-breast feeding at the time of insertion. Adjusted relative risks estimated by odds ratios are 2.1, 2.7, 2.7, and 5.0 respectively. For women with a combination of the above risk factors, they have a further increased (additive in nature) risk of suffering severe insertion pain. Similar analysis was also performed on a developed country center data set for which only the effect of education and parity could be studied; an odds ratio of 5.0 for nulliparity was obtained. Better educated women are probably less inhibited to complain of pain than less-educated women. A tighter uterine cervix and a smaller uterine cavity in women of low parity may account for IUD insertion pain. Postpartum involution of the uterus could explain pain upon insertion for women with a long open interval. These findings support the hypothesis that cervical stretching and direct endometrial pressure are probably the most important factors for IUD insertion pain.

Migration of IUD from the corpus uteri occurs in approximately 1/2500 applications. Primary migration of the IUD is associated with perforation of the uterine wall. Secondary migration of a properly inserted IUD is caused by uterine contraction. Diagnosis of IUD migration can be made following pelvic x-ray examination (hysterography, cystography), irrigoscopy, echography, and finally, laparoscopy. Difficulties encountered during diagnosis of IUD migration are illustrated by a case history of a 24-year old woman. After the birth of her 2nd child, the patient received application of the Lippes IUD; the patient experienced pain during application and for the next 10 days. The patient was seen 14 months after IUD insertion with a 2-month history of amenorrhea. A pregnancy of 7-weeks gestation was diagnosed. During termination of pregnancy, the IUD could not be detected. Subsequent examination of an extremely wide and long cervical canal revealed the limbs of the device in the posterior fornix of the cervix uteri, approximately 7-8 mm above the wide uterine ligament. Conventional posterior-anterior x-ray examination of the lesser pelvis showed the presence of the IUD. These findings were confirmed at hysterography and cystography. The patient underwent exploratory laparotomy, and the IUD was removed. It was concluded that difficulties with insertion of the IUD were associated with anatomical abnormalities of the cervix uteri. It was emphasized that women with abnormal size of the vagina have a risk of asymptomatic extraperitoneal migration of the IUD.