Antley-Bixler syndrome
Encyclopedia
Antley-Bixler syndrome, also called trapezoidocephaly-synostosis syndrome, is a rare, very severe autosomal recessive
congenital disorder
characterized by malformations and deformities affecting the majority of the skeleton and other areas of the body.
(flat forehead), craniosynostosis
(complete skull-joint closure) of both coronal
and lambdoid suture
s, facial hypoplasia
(underdevelopment); bowed ulna
(forearm bone) and femur
(thigh bone), synostosis
of the radius
(forearm bone), humerus
(upper arm bone), and trapezoid
(hand bone); camptodactyly
(fused interphalangeal joint
s in the fingers), thin ilial wings
(outer pelvic plate), and renal malformations.
Other symptoms, such as cardiac malformations, proptotic exophthalmos
(bulging eyes), arachnodactyly
(spider-like fingers), as well as nasal
, anal
, and vaginal atresia
(occlusion) have been reported.
There are two distinct gene
tic mutation
s associated with the Antley-Bixler syndrome phenotype
, which suggests the disorder may be heterogeneous.
Antley-Bixler syndrome is inherited in an autosomal recessive
pattern, which means the defective gene is located on an autosome
, and two copies of the gene (one inherited from each parent) are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene but are usually not affected by the disorder.
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
congenital disorder
Congenital disorder
A congenital disorder, or congenital disease, is a condition existing at birth and often before birth, or that develops during the first month of life , regardless of causation...
characterized by malformations and deformities affecting the majority of the skeleton and other areas of the body.
Presentation
Antley-Bixler syndrome presents itself at birth or prenatally. Features of the disorder include brachycephalyBrachycephaly
Brachycephaly, also known as flat head syndrome, is a type of cephalic disorder. This can result from premature fusion of the coronal sutures or from external deformation . The coronal suture is the fibrous joint that unites the frontal bone with the two parietal bones of the skull. The parietal...
(flat forehead), craniosynostosis
Craniosynostosis
Craniosynostosis is a condition in which one or more of the fibrous sutures in an infant skull prematurely fuses by ossification, thereby changing the growth pattern of the skull...
(complete skull-joint closure) of both coronal
Coronal suture
The coronal suture is a dense, fibrous connective tissue joint that separates the frontal and parietal bones of the skull. At birth, the bones of the skull do not meet.-Pathology:...
and lambdoid suture
Lambdoid suture
The lambdoid suture is a dense, fibrous connective tissue joint on the posterior aspect of the skull that connects the parietal and temporal bones with the occipital bone.Its name comes from its lambda-like shape....
s, facial hypoplasia
Hypoplasia
Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia...
(underdevelopment); bowed ulna
Ulna
The ulna is one of the two long bones in the forearm, the other being the radius. It is prismatic in form and runs parallel to the radius, which is shorter and smaller. In anatomical position The ulna is one of the two long bones in the forearm, the other being the radius. It is prismatic in form...
(forearm bone) and femur
Femur
The femur , or thigh bone, is the most proximal bone of the leg in tetrapod vertebrates capable of walking or jumping, such as most land mammals, birds, many reptiles such as lizards, and amphibians such as frogs. In vertebrates with four legs such as dogs and horses, the femur is found only in...
(thigh bone), synostosis
Synostosis
Synostosis is the abnormal fusion of neighbor bones. It is a type of dysostosis.Examples of synostoses include: craniosynostosis- being an abnormal fusion of two or more cranial bones, radio-ulnar synostosis- being the abnormal fusion of the radius and ulna bones of the forearm, tarsal coalition -...
of the radius
Radius
In classical geometry, a radius of a circle or sphere is any line segment from its center to its perimeter. By extension, the radius of a circle or sphere is the length of any such segment, which is half the diameter. If the object does not have an obvious center, the term may refer to its...
(forearm bone), humerus
Humerus
The humerus is a long bone in the arm or forelimb that runs from the shoulder to the elbow....
(upper arm bone), and trapezoid
Trapezoid bone
The trapezoid bone is a carpal bone in tetrapods, including humans. It is the smallest bone in the distal row. It may be known by its wedge-shaped form, the broad end of the wedge constituting the dorsal, the narrow end the palmar surface; and by its having four articular facets touching each...
(hand bone); camptodactyly
Camptodactyly
Camptodactyly is a medical condition involving fixed flexion deformity of the interphalangeal joints of the little finger. This involves permanent flexure of one or more phalanges...
(fused interphalangeal joint
Interphalangeal joint
Interphalangeal joint may refer to:*Interphalangeal articulations of hand*Interphalangeal articulations of foot...
s in the fingers), thin ilial wings
Wing of ilium
The wing of ilium is the large expanded portion which bounds the greater pelvis laterally. It presents for examination two surfaces—an external and an internal—a crest, and two borders—an anterior and a posterior.-External surface:...
(outer pelvic plate), and renal malformations.
Other symptoms, such as cardiac malformations, proptotic exophthalmos
Exophthalmos
Exophthalmos is a bulging of the eye anteriorly out of the orbit. Exophthalmos can be either bilateral or unilateral . Measurement of the degree of exophthalmos is performed using an exophthalmometer...
(bulging eyes), arachnodactyly
Arachnodactyly
Arachnodactyly or achromachia, is a condition in which the fingers are abnormally long and slender in comparison to the palm of the hand...
(spider-like fingers), as well as nasal
Choanal atresia
Choanal atresia is a congenital disorder where the back of the nasal passage is blocked, usually by abnormal bony or soft tissue formed during fetal development.-Presentation:It can be unilateral or bilateral....
, anal
Imperforate anus
An imperforate anus or anal atresia is a birth defect in which the rectum is malformed. Its cause is unknown.-Features:There are several forms of imperforate anus:* A low lesion, in which the colon remains close to the skin...
, and vaginal atresia
Vaginal atresia
Vaginal Atresia is a birth defect or congenital abnormality of the female genitourinary system that manifests itself in the absence of a vagina , or a deformed and nonfunctional vagina ....
(occlusion) have been reported.
Pathophysiology
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
tic mutation
Mutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s associated with the Antley-Bixler syndrome phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
, which suggests the disorder may be heterogeneous.
| OMIM | Gene | Description |
|---|---|---|
| FGFR2 | Mutations found in the FGFR2 Fibroblast growth factor receptor 2 Fibroblast growth factor receptor 2 also known as CD332 is a protein that in humans is encoded by the FGFR2 gene residing on chromosome 10... gene have been shown to cause synostosis Synostosis Synostosis is the abnormal fusion of neighbor bones. It is a type of dysostosis.Examples of synostoses include: craniosynostosis- being an abnormal fusion of two or more cranial bones, radio-ulnar synostosis- being the abnormal fusion of the radius and ulna bones of the forearm, tarsal coalition -... and other formal skeletal, poly Polydactyly Polydactyly or polydactylism , also known as hyperdactyly, is a congenital physical anomaly in humans, dogs, and cats having supernumerary fingers or toes.... and syndactylic Syndactyly Syndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans.-Classification:... abnormalities found in Antley-Bixler and similar disorders. |
|
| POR Cytochrome P450 reductase Cytochrome P450 reductase is a membrane-bound enzyme required for electron transfer to cytochrome P450 in the microsome of the eukaryotic cell from a FAD- and FMN-containing enzyme NADPH:cytochrome P450 reductase .-Introduction:... |
A missense mutation Missense mutation In genetics, a missense mutation is a point mutation in which a single nucleotide is changed, resulting in a codon that codes for a different amino acid . This can render the resulting protein nonfunctional... in the cytochrome p450 oxydoreductase (POR) gene results in abnormal steroidogenesis related to the genital malformations often found in Antley-Bixler. In OMIM, this is classified as an "Antley-Bixler syndrome-like phenotype" and not as Antley-Bixler syndrome itself. |
|
Antley-Bixler syndrome is inherited in an autosomal recessive
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
pattern, which means the defective gene is located on an autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
, and two copies of the gene (one inherited from each parent) are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene but are usually not affected by the disorder.