X-linked agammaglobulinemia (XLA) is a rare genetic disorder discovered in 1952 that affects the body's ability to fight infection. As the form of agammaglobulinemia that is X-linked, it is much more common in males. In people with XLA, the white blood cell formation process does not generate mature B cells, which manifests as a complete or near-complete lack of proteins called gamma globulins, including antibodies, in their bloodstream. B cells are part of the immune system and normally manufacture antibodies, which defend the body from infections by sustaining a humoral immunity response. Patients with untreated XLA are prone to develop serious and even fatal infections. A mutation occurs at the Bruton's tyrosine kinase (Btk) gene that leads to a severe block in B cell development and a reduced immunoglobulin production in the serum. Btk is particularly responsible for mediating B cell development and maturation through a signaling effect on the B cell receptor BCR. Patients typically present in early childhood with recurrent infections, in particular with extracellular, encapsulated bacteria. XLA is deemed to have a relatively low incidence of disease, with an occurrence rate of approximately 1 in 200,000 live births and a frequency of about 1 in 100,000 male newborns. It has no ethnic predisposition. XLA is treated by infusion of human antibody. Treatment with pooled gamma globulin cannot restore a functional population of B cells, but it is sufficient to reduce the severity and number of infections due to the passive immunity granted by the exogenous antibodies.
Spondyloepiphyseal dysplasia congenita is a rare disorder of bone growth that results in dwarfism, characteristic skeletal abnormalities, and occasionally problems with vision and hearing. The name of the condition indicates that it affects the bones of the spine (spondylo-) and the ends of bones (epiphyses), and that it is present from birth (congenital). The signs and symptoms of spondyloepiphyseal dysplasia congenita are similar to, but milder than, the related skeletal disorders achondrogenesis type 2 and hypochondrogenesis. Spondyloepiphyseal dysplasia congenita is a subtype of collagenopathy, types II and XI.
Hypochondroplasia (HCH) is a developmental disorder caused by an autosomal dominant genetic defect in the fibroblast growth factor receptor 3 gene (FGFR3) that results in a disproportionately short stature, micromelia and a head that appears large in comparison with the underdeveloped portions of the body. It is classified as short-limbed dwarfism.
Cartilage–hair hypoplasia (CHH) is a rare genetic disorder. Symptoms may include short-limbed dwarfism due to skeletal dysplasia, variable level of immunodeficiency, and predisposition to cancer. It was first reported by Victor McKusick in 1965.
McCune–Albright syndrome is a complex genetic disorder affecting the bone, skin and endocrine systems. It is a mosaic disease arising from somatic activating mutations in GNAS, which encodes the alpha-subunit of the Gs heterotrimeric G protein.
An osteochondrodysplasia, or skeletal dysplasia, is a disorder of the development of bone and cartilage. Osteochondrodysplasias are rare diseases. About 1 in 5,000 babies are born with some type of skeletal dysplasia. Nonetheless, if taken collectively, genetic skeletal dysplasias or osteochondrodysplasias comprise a recognizable group of genetically determined disorders with generalized skeletal affection. These disorders lead to disproportionate short stature and bone abnormalities, particularly in the arms, legs, and spine. Skeletal dysplasia can result in marked functional limitation and even mortality.
Pseudoachondroplasia is an inherited disorder of bone growth. It is a genetic autosomal dominant disorder. It is generally not discovered until 2–3 years of age, since growth is normal at first. Pseudoachondroplasia is usually first detected by a drop of linear growth in contrast to peers, a waddling gait or arising lower limb deformities.
Ghosal hematodiaphyseal dysplasia, is a rare, autosomal recessive disease, characterized by diaphyseal dysplasia and metaphyseal dysplasia of the long bones and refractory anemia.
Parastremmatic dwarfism is a rare bone disease that features severe dwarfism, thoracic kyphosis, a distortion and twisting of the limbs, contractures of the large joints, malformations of the vertebrae and pelvis, and incontinence. The disease was first reported in 1970 by Leonard Langer and associates; they used the term parastremmatic from the Greek parastremma, or distorted limbs, to describe it. On X-rays, the disease is distinguished by a "flocky" or lace-like appearance to the bones. The disease is congenital, which means it is apparent at birth. It is caused by a mutation in the TRPV4 gene, located on chromosome 12 in humans. The disease is inherited in an autosomal dominant manner.
Eiken syndrome, also known as "Eiken skeletal dysplasia", is a rare autosomal bone dysplasia with a skeletal phenotype which has been described in a unique consanguineous family, where it segregates as a recessive trait. First described in 1985, the syndrome primarily affects the development of bones, leading to short stature, long limbs, and joint dislocations. Eiken syndrome is caused by mutations in the PTH1R gene, located on chromosome 3, and is involved in skeletal development.
Severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN) is a very rare genetic disorder. This disorder is one that affects bone growth and is characterized by skeletal, brain, and skin abnormalities. Those affected by the disorder are severely short in height and commonly possess shorter arms and legs. In addition, the bones of the legs are often bowed and the affected have smaller chests with shorter rib bones, along with curved collarbones. Other symptoms of the disorder include broad fingers and extra folds of skin on the arms and legs. Developmentally, many individuals who suffer from the disorder show a higher level in delays and disability. Seizures are also common due to structural abnormalities of the brain. Those affected may also suffer with apnea, the slowing or loss of breath for short periods of time.
Cousin syndrome is a genetic condition characterized by short stature at birth, a short neck with low-positioned external ears, as well as congenital malformations of the skeletal system affecting the shoulders, the pelvis, the neck, and the limbs. The condition determines physical disability, particularly affecting deambulation, and hearing loss while intelligence is not affected.
Familial osteodysplasia, Anderson type is a rare genetic disorder which is characterized by cranio-facial dysmorphisms and multiple skeletal anomalies. Hyperuricemia, hypertension and high erythrocyte sedimentation rates have also been reported. Approximately 6 cases have been reported in medical literature. This disorder is thought to be inherited in an autosomal recessive manner.
Rhizomelic dysplasia, scoliosis, and retinitis pigmentosa is a very rare genetic disorder which is characterized by ocular/visual, dental and osseous anomalies. Only 2 cases have been described in medical literature.
Spondyloepimetaphyseal dysplasia-short limb-abnormal calcification syndrome is a rare genetic disorder which is characterized by osseous anomalies resulting in short stature and other afflictions.
Wormian bone-multiple fractures-dentinogenesis imperfecta-skeletal dysplasia syndrome is a rare genetic bone disorder which is characterized by the presence of wormian bones in the skull, dentinogenesis imperfecta, recurrent bone fractures, hypertelorism, and eye puffiness. This disorder is unique from osteogenesis imperfecta because of the presence of cortical defects and the absence of defective collagen or osteopenia. It is not exactly known whether this condition is autosomal dominant or autosomal recessive.
Schneckenbecken dysplasia is a rare pre-natally fatal hereditary autosomal recessive condition which affects the bones and pre-natal growth.
Hall-Riggs syndrome is a rare genetic disorder that causes neurological issues and birth defects. People with Hall-Riggs syndrome usually have skeletal dysplasia, facial deformities, and intellectual disabilities. Only 8 cases from 2 families worldwide have been described in medical literature. It is an autosomal recessive genetic disorder, meaning both parents must carry the gene in order for their offspring to be affected.
Spondyloenchondrodysplasia is the medical term for a rare spectrum of symptoms that are inherited following an autosomal recessive inheritance pattern. Skeletal anomalies are the usual symptoms of the disorder, although its phenotypical nature is highly variable among patients with the condition, including symptoms such as muscle spasticity or thrombocytopenia purpura. It is a type of immunoosseous dysplasia.
