Osteogenesis imperfecta (OI) is a congenital skeletal disorder characterized by varying degrees of bone fragility and deformities. (A) fracture of bilateral humeri in a neonate with OI caused by a pathogenic variant in the COL1A1 gene, (B) calcification of the interosseous membrane in a patient with type 5 OI caused by a specific pathogenic variant, c.-14C>T, in the IFITM5 gene. (C) Mechanism of type I collagen synthesis. Many genes involved in this process have been identified as causative factors of OI, such as the type 1 collagen gene and genes involved in folding (P3H1, CRTAP, and PPIB), collagen processing and crosslinking of type I collagen molecules (SERPINH1, FKBP10, PLOD2, and BMP1), osteoblast differentiation (SP7, TMEM38B, WNT1, CREB3L1, SPARC, and MBTPS2), and bone mineralization (IFITM5 and SERPINF1). ADAMTS-2, a disintegrin and metalloproteinase with thrombospondin motifs 2; BRIL, bone-restricted Ifitm-like; BMP1, bone morphogenetic protein; FKBP65, 65-kDa FK506-binding protein; HSP47, heat shock protein 47; KDELR2, KDEL endoplasmic reticulum protein retention receptor 2; P3H, Prolyl 3-hydroxylase; P4H, prolyl 4-hydroxylase; PEDF, pigment epithelium-derived factor; PICP, carboxyterminal propeptides of type I collagen; PINP, aminoterminal propeptides of type I collagen; SPARC, secreted protein acidic and rich in cysteine.

Pendred syndrome is a genetic condition characterized by congenital sensorineural hearing loss and thyroid abnormalities resulting from a deficiency of pendrin, encoded by the SLC26A4 gene. This deficiency disrupts iodide utilization, which is necessary for thyroid hormone synthesis, potentially leading to partial organification defects. The hearing impairment associated with Pendred syndrome constitutes 4–10% of cases of congenital deafness, primarily due to inner ear abnormalities. Imaging studies, such as CT and MRI may reveal modiolus deficiency, an enlarged vestibular aqueduct, and cochlear dysplasia. A 13-year-old girl with Pendred syndrome and a history of bilateral hearing loss since the age of 4 years presented with goiter. (a, b) Ultrasound showing thyroid enlargement associated with increased vascularity. (c) MRI showing vestibular aqueduct enlargement (arrow).

In this cohort, we investigated the mortality rate and standardized mortality ratio (SMR) among all patients who developed type 1 diabetes at age <15 years from 1959 to 1996 in Hokkaido Prefecture, Japan. Out of 521 enrolled patients, we analyzed the data of 391 whose attending physicians replied to our survey. Mortality rates per 100,000 person-years and SMRs were 475 and 6.9 for all patients, 559 and 8.5 for men, and 424 and 6.0 for women, respectively. For the time of onset of type 1 diabetes, these variables were 823 and 8.8 between 1959 and 1979, 370 and 5.9 between 1980 and 1989, and 133 and 3.2 between 1990 and 1996, respectively. Mortality rates per 100,000 person-years and SMRs were 452 and 7.3 for onset before puberty and 514 and 6.3 for onset after puberty, respectively, and 480 and 7.1 for the acute-onset subtype and 428 and 5.6 for the incidentally detected non-acute-onset subtype, respectively. Upon survival analysis, we observed no difference in mortality or lifespan between the sexes. Mortality and lifespan were not different between pre- and postpubertal onset and did not differ between the subtypes of type 1 diabetes.