Ans. A. Osteogenesis imperfecta. (Ref. H - 17th/pg. 2411)Blue sclera is a distinct feature of OGLSCLEROSING BONE DISORDERS# OSTEOPETROSIS# PYKNODYSOSTOSIS# PROGRESSIVE DIAPHYSEAL DYSPLASIA (Camurati-Engelman disease)# HYPEROSTOSIS CORTICALIS GENERALISATA (van Buchem disease)# MELORHEOSTOSIS (Greek, "flowing hyperostosis")# OSTEOPOIKILOSIS ("spotted bones")# Hepatitis C-associated osteosclerosis (HCAO)Pyknodysostosis :# Pyknodysostosis is a form of short-limb dwarfism that presents with frequent fractures but usually normal lifespan. Clinical features include short stature; kyphoscoliosis and deformities of the chest; high arched palate; proptosis; blue sclerae; dysmorphic features including small face and chin, frontooccipital prominence, pointed beaked nose, large cranium, and obtuse mandibular angle; and small square hands with hypoplastic nails. Radiographs demonstrate a generalized increase in bone density, but in contrast to osteopetrosis, the long bones are normally shaped. Separated cranial sutures, including the persistent patency of the anterior fontanel, are characteristic of the disorder. There may also be hypoplasia of the sinuses, mandible, distal clavicles, and terminal phalanges. Persistence of deciduous teeth and sclerosis of the calvarium and base of the skull are also common.Anchondo dysplasia:# This is a relatively common form of short-limb dwarfism that occurs in 1 in 15,000 to 1 in 40,000 live births. The disease is caused by a mutation of the fibroblast growth factor receptor 3 (FGFR3) gene that results in a gain-of-function state. Most cases are sporadic mutations. However, when the disorder appears in families, the inheritance pattern is consistent with an autosomal dominant disorder. The primary defect is abnormal chondrocyte proliferation at the growth plate that causes the development of short but proportionately thick long bones. Other regions of the long bones may be relatively unaffected. The disorder is manifest by the presence of short limbs (particularly the proximal portions), normal trunk, large head, saddle nose, and an exaggerated lumbar lordosis. Severe spinal deformity may lead to cord compression. The homozygous disorder is more serious than the sporadic form and may cause neonatal death. Pseudo-achondroplasia clinically resembles achondroplasia but has no skull abnormalities.Osteopetrosis (marble bone disease):# Osteopetrosis refers to a group of disorders caused by severe impairment of osteoclast-mediated bone resorption. There is the solid x-ray appearance of the involved skeleton, o Diaphyses and metaphyses are broadened, and alternating sclerotic and lucent bands may be seen in the iliac crests, at the ends of long bones, and in vertebral bodies. The cranium is usually thickened, particularly at the base of the skull, and the paranasal and mastoid sinuses are under pneumatized. Albers-Schonberg disease refers to the milder, adult form of osteopetrosis (autosomal dominant osteopetrosis type II). Mice deficient in RANK lack osteoclasts and develop severe osteopetrosis. As bone and cartilage fail to undergo modeling, paralysis of one or more cranial nerves may occur due to narrowing of the cranial foramina. Failure of skeletal modeling also results in inadequate marrow space, leading to extramedullary hematopoiesis with hypersplenism and pancytopenia. Hypocalcemia due to lack of osteoclastic bone resorption may occur in infants and young children. The untreated infantile disease is fatal, often before age 5. The course is not always benign, as fractures may be accompanied by blue sclerae, loss of vision, deafness, psychomotor delay, mandibular osteomyelitis, and other complications usually associated with the juvenile form. /gjt: Allogenic HLA-identical bone marrow transplantation has been successful in some children. Following transplantation, the marrow contains progenitor cells and normally functioning osteoclasts. A cure is most likely when children are transplanted before age 4.