INTRODUCTION

Neurofibromatosis type 1 (NF1) is an autosomal dominantly inherited condition seen in one of 4000 live births, predisposing to peripheral and central neurofibromas. Spinal tumors are seen in 40% of cases with NF1 and only 2% will develop symptoms, and among those who develop symptoms where 33% showed intradural extramedullary location. Thoracic spinal dumbbell neurofibroma is even rarer, and cases that extend to obliterate the posterior mediastinum even more so, with the case presented being the largest in size documented to date.

A 34-year-old female presented since childhood clinical findings consistent with Neurofibromatosis Type I: generalized cafe-au-lait macules, axillary freckling, cutaneous neurofibromas, two iris Lisch nodules identified via slit lamp examination, and anterolateral bowing of the right tibia, and no known parental history of Neurofibromatosis Type I. Prior to admission, the patient presented with progressive loss of motor strength of the lower extremities, and progressive dyspnea. Work-up revealed a Thoracic Intradural Extramedullary Neurofibroma extending to the Right Posterior Mediastinum measuring 15.3 cm x 12.9 cm x 9.7 cm in the thoracic cavity compressing the right lung and bronchus. An extensive two stage surgery was contemplated involving an initial resection of the Intradural mass, with spine instrumentation for support, and subsequent resection of the mediastinal extension. However, complications from the compressing tumor: complete cord transection syndrome causing spinal autonomic dysfunction, lung and airway compromise causing prolonged intubation and difficulty in weaning from mechanical ventilatory support, extensive thrombus formation in the right jugular vein, and nosocomial infections all created compounding difficulties for the surgical technique and anesthetic plan.

Cornerstone management for dumbbell spinal neurofibromas involves their total removal. The best results are obtained in patients showing minimal neurological deficits during the preoperative period. However, little improvement may be expected from patients who develop complete transection syndrome during the postoperative period. Concurrent medical management to prepare the patients are equally important. The multi-subspecialty approach required in managing these cases entails a good balance between the disability before the surgery, anticipated outcomes, and quality of life of the patients.

Y chromosome microdeletions are an important cause of male infertility. At present, research on the Y chromosome is mainly focused on analyzing the loss of large segments of the azoospermia factor a/b/c (AZFa/b/c) gene, and few studies have reported the impact of unit point deletion in the AZF band on fertility. This study analyzed the effect of sperm quality after sY1192 loss in 116 patients. The sY1192-independent deletion accounted for 41.4% (48/116). Eight patterns were found in the deletions associated with sY1192. The rate of sperm detection was similar in the semen of patients with the independent sY1192 deletion and the combined sY1192 deletions (52.1% vs 50.0%). The patients with only sY1192 gene loss had a higher probability of sperm detection than the patients whose sY1192 gene locus existed, but other gene loci were lost (52.1% vs 32.0%). The hormone levels were similar in patients with sY1192 deletion alone and in those with sY1192 deletion and other types of microdeletions in the presence of the sY1192 locus. After multiple intracytoplasmic sperm injection (ICSI) attempts, the pregnancy rate of spouses of men with sY1192-independent deletions was similar to that of other types of microdeletions, but the fertilization and cleavage rates were higher. We observed that eight deletion patterns were observed for sY1192 microdeletions of AZFb/c, dominated by the independent deletion of sY1192. After ICSI, the fertilization rate and cleavage rate of the sY1192-independent microdeletion were higher than those of other Y chromosome microdeletion types, but there was no significant difference in pregnancy outcomes.
Humans ; Female ; Pregnancy ; Male ; Chromosomes, Human, Y/genetics* ; Adult ; Chromosome Deletion ; Pregnancy Outcome/genetics* ; Infertility, Male/genetics* ; Spermatozoa/physiology* ; Semen Analysis ; Sex Chromosome Disorders of Sex Development/genetics* ; Sperm Injections, Intracytoplasmic ; Azoospermia/genetics* ; Sex Chromosome Aberrations

Duchenne muscular dystrophy (DMD) is an X-linked recessive neuromuscular disorder characterized primarily by progressive degeneration and necrosis of skeletal muscle, resulting from mutations in the <i>Dystrophini> gene. Patients with DMD typically present with progressive muscle weakness and atrophy during childhood. Currently, available treatment options for DMD remain limited and their efficacy is suboptimal. This review aims to provide a systematic overview of recent advances in therapeutic strategies for DMD, including an analysis of the mechanisms underlying various treatment approaches, outcomes from clinical trials, and their potential clinical applications, in order to inform and guide clinical decision-making.
Muscular Dystrophy, Duchenne/genetics* ; Humans ; Genetic Therapy

Case 1 was a 7-year-old girl; Case 2 was her 3-year-old younger brother. Both children developed pink urine shortly after birth and exhibited blistering on photo-exposed areas (face and hands), followed by ulceration, crusting, scarring, and joint contractures leading to impaired mobility. Genetic testing in both patients identified a homozygous variant in the <i>UROSi> gene, c.776T>C (p.Leu259Pro), confirming autosomal recessive congenital erythropoietic porphyria due to <i>UROSi> mutations. This case report highlights that congenital erythropoietic porphyria should be considered in infants and young children with unexplained hemolytic anemia, pink urine, and severe photosensitive dermatitis. Early genetic testing is recommended to facilitate timely intervention and improve outcomes.
Humans ; Porphyria, Erythropoietic/genetics* ; Female ; Child ; Child, Preschool ; Male ; Siblings ; Mutation ; Uroporphyrinogen III Synthetase/genetics*

OBJECTIVE: To analyze the effect of Y chromosome AZFc microdeletion on pregnancy outcome of intracytoplasmic sperm injection (ICSI). METHODS: From 2016 to 2023, 6 765 cases of oligozoospermia in our hospital were selected as the research objects. The results of Y chromosome microdeletion test were retrospectively analyzed. According to the inclusion exclusion criteria and the principle of propensity distribution 1∶2, 180 patients were included in the study. Sixty patients with Y chromosome AZFc microdeletion and ICSI assisted pregnancy were enrolled into the experimental group. The other 120 patients without Y chromosome microdeletion and ICSI assisted pregnancy were included in the control group. Baseline characteristics, five male sex hormones, laboratory embryo culture and pregnancy outcomes were compared between the two groups. RESULTS: There was no significant difference in male age, female age, infertility years, gravidity and parity between the two groups (P>0.05). There was no significant difference in the five sex hormones of men (P>0.05). Except for transplantable embryos (P<0.05), there was no significant difference in other indicators in the process of embryo culture. There was no difference in pregnancy outcome indicators between the two groups except for the preterm birth rate (P<0.05). CONCLUSION ICSI assisted pregnancy with Y chromosome AZFc microdeletion has no significant effect on pregnancy outcome. And close follow-up of offspring is required.
Humans ; Sperm Injections, Intracytoplasmic ; Pregnancy ; Female ; Chromosomes, Human, Y ; Male ; Chromosome Deletion ; Pregnancy Outcome ; Retrospective Studies ; Sex Chromosome Disorders of Sex Development ; Sex Chromosome Aberrations ; Adult ; Infertility, Male/genetics* ; Oligospermia/genetics* ; Pregnancy Rate

Neurofibromatosis Type 1 （NF1） is an autosomal dominant hereditary neurological disorder. One of the typical manifestations of NF1 is neurofibroma, which can develop gradually over time. When the volume exceeds 100 cm², it is referred to as giant neurofibroma, representing a tumor-like proliferation of Schwann cells within the nerve fiber sheath. The Department of Otolaryngology at the Affiliated Hospital of Guangdong Medical University received a rare case involving a patient with giant neurofibromatosis affecting the maxillofacial region, neck, and chest. The patient underwent successful surgical treatment with the collaboration of various medical disciplines.
Humans ; Head and Neck Neoplasms/surgery* ; Neck ; Neurofibromatoses ; Neurofibromatosis 1/surgery* ; Thoracic Neoplasms/surgery*

Crigler-Najjar syndrome (CNS) and Gilbert syndrome (GS; OMIM: 143500) are rare autosomal recessive diseases that cause unconjugated hyperbilirubinemia due to decreased UGT1A1 enzyme activity. Crigler-Najjar syndrome type 2 (CNS2; OMIM: 606785) increases the risk of gallbladder stone formation and cholecystitis, while GS seldom causes health issues. We found a 28-year-old male patient with recurring right upper abdomen pain who experienced persistent jaundice from birth. CNS2 with gallbladder stones and cholecystitis was diagnosed after genetic testing revealed rare double homozygous mutations A(TA)₇TAA (rs3064744) and P229Q (rs35350960) in the UGT1A1 gene. After pedigree investigation, we found that the patient's parents with modestly increased bilirubin had compound heterozygous mutations A(TA)₇TAA and P229Q, which were GS. Bioinformatics analysis showed that A(TA)₇TAA is in the TATA-box region of the gene UGT1A1 promoter, affecting gene transcriptional initiation, whereas P229Q modifies protein three-dimensional structure and may be harmful. In this pedigree, double homozygous mutations have a more severe phenotype than compound heterozygous mutations. Inherited causes of hyperbilirubinemia should be suspected after ruling out biliary obstruction, and early bilirubin reduction (< 103 µmol/L (6 mg/dL)) may reduce the risk of complications like cholecystitis in CNS2 patients, though further studies with longer follow-up are needed to confirm this observation.
Humans ; Male ; Glucuronosyltransferase/genetics* ; Adult ; Crigler-Najjar Syndrome/complications* ; Cholecystitis/etiology* ; Homozygote ; Mutation ; Pedigree

Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy caused by mutations in the dystrophin gene, which is divided into presymptomatic, early ambulatory, late ambulatory, early non-ambulatory, and late non-ambulatory stages according to its disease progression. Some patients experience non-progressive cognitive developmental delays in the presymptomatic stage. DMD patients gradually develop osteoporosis, cardiomyopathy, decreased respiratory function, delayed puberty, and gastrointestinal symptoms as the disease progresses. The required multidisciplinary management strategies vary across different disease stages. To standardize the multidisciplinary management of DMD, we established the DMD Guideline Writing Committee under the authorization of Chinese Medical Association Rare Disease Branch. Combined with the questions raised by patients in multiple consultations, neuromuscular experts drafted the DMD guidelines based on published clinical evidence, current practices, and expert recommendations. A consensus was reached on the best-practice recommendations for DMD management after extensive consultations with specialists from multiple relevant disciplines. The resulting recommendations have been endorsed by Chinese Medical Association Rare Disease Branch. This guideline provides practical and reasonable recommendations for all healthcare professionals and caregivers involved in DMD management, ensuring that patients can receive high-standard medical treatment and care across our country, which also serves as a reference for government staff involved in DMD management.
Humans ; Muscular Dystrophy, Duchenne/therapy* ; China

Disorders of sex development (DSD) are characterized by atypical development of chromosomal, gonadal, or phenotypic sex. 45X,46XY mosaicism is a type of sex chromosome DSD which presents with a wide heterogeneity of manifestations. We report the case of a 13-year-old phenotypically female who presented with clitoromegaly at puberty. Testosterone level was elevated on serology. Out of the 50 cells examined, 43 cells had Monosomy X while 7 cells had a normal male karyotype. She was managed by a multidisciplinary team. Due to the presence of Y chromosome, the solid nodular structure seen on the right gonad in magnetic resonance imaging and the pain caused by the phallus, Laparoscopic bilateral gonadectomy, salpingectomy and clitoroplasty were done after a shared decision making. Histopathology revealed Gonadoblastoma and Germ cell neoplasia-in-situ of the right gonad justifying timely removal. She was then maintained on estrogen for induction of secondary sexual characteristics.

Junctional Epidermolysis Bullosa (JEB) is a rare inherited blistering disorder characterized by extreme skin fragility. It is associated with COL17A1 mutation that is critical for dermoepidermal adhesion. Effective management in resource-limited settings is challenging and focuses on wound care and trauma prevention to prevent complications and improve quality of life.

A 27-year-old Filipino female presented with recurrent blisters and erosions since infancy, accompanied by diffuse alopecia and anonychia of the toenails. On physical examination, she presented with multiple, well-defined, erythematous tense vesicles and bullae on the trunk, upper and lower extremities which were triggered by minor trauma to the skin. Skin punch biopsy was done revealing a subepidermal blistering dermatosis while direct immunofluorescence (DIF) and Enzyme-Linked Immunosorbent Assay (ELISA) tests for BP180, BP230, and type VII collagen were negative. Genetic testing was done and revealed compound heterozygous mutations in the COL17A1 gene, consistent with JEB. She was managed with non-adhesive dressings, sterile aspiration of blisters, and nutritional support. Despite the severity of her condition, the patient experienced significant improvement in wound healing and quality of life through meticulous wound care, trauma prevention and nutritional support.

This case highlights the unusual case of a 27-year-old Filipino female with JEB who has survived into adulthood, a rarity given the typically poor prognosis associated with severe forms of the disease.