Liebenberg syndrome is a rare

autosomal An autosome is any chromosome that is not a sex chromosome. The members of an autosome pair in a diploid cell have the same morphology, unlike those in allosome, allosomal (sex chromosome) pairs, which may have different structures. The DNA in au ...

genetic disease that involves a

deletion mutation In genetics, a deletion (also called gene deletion, deficiency, or deletion mutation) (sign: Δ) is a mutation (a genetic aberration) in which a part of a chromosome or a sequence of DNA is left out during DNA replication. Any number of nucleoti ...

upstream of the PITX1 gene, which is one that's responsible for the body's organization, specifically in forming lower limbs. In animal studies, when this deletion was introduced to developing birds, their wing buds were noted to take on limb-like structures. The condition was first described by Dr. F. Liebenberg in 1973 while he followed multiple generations of a South African family,Liebenberg, F., 1973. A pedigree with unusual anomalies of the elbows, wrist, and hands in fine generations. S. Afr. Med. J. 47, 745–747. Accessed October 4, 2015. but it has since been noticed in other family lineages across the world.

Symptoms and signs

People who are affected by Liebenberg Syndrome suffer from three main symptoms: #

Dysplasia Dysplasia is any of various types of abnormal growth or development of cells (microscopic scale) or organs (macroscopic scale), and the abnormal histology or anatomical structure(s) resulting from such growth. Dysplasias on a mainly microscopic ...

(improper formation) of the bony components of the elbow # Abnormal shape of

carpal bones The carpal bones are the eight small bones that make up the wrist (or carpus) that connects the hand to the forearm. The term "carpus" is derived from the Latin carpus and the Greek καρπός (karpós), meaning "wrist". In human anatomy, th ...

Brachydactyly Brachydactyly (Greek βραχύς = "short" plus δάκτυλος = "finger"), is a medical term which literally means "short finger". The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an in ...

, a symptom where the fingers and toes are shorter than normal.

Phenotype

People with Liebenberg Syndrome have normal overall body structure. Their morphological differences are in both of their distal humeri, elbows, hands and wrists. The elbows are enlarged with abnormally large

olecranon The olecranon (, ), is a large, thick, curved bony eminence of the ulna, a long bone in the forearm that projects behind the elbow. It forms the most pointed portion of the elbow and is opposite to the cubital fossa or elbow pit. The olecranon ...

s and radial heads. Patients have relatively fixed elbow positions and are therefore unable to

pronate Motion, the process of movement, is described using specific anatomical terminology, anatomical terms. Motion includes movement of Organ (anatomy), organs, joints, Limb (anatomy), limbs, and specific sections of the body. The terminology used de ...

or supinate their forearms. Their wrists are also limited in their active movements and have very prominent ulnar sides of the joints. The fingers adopt toe-like structures.

and

camptodactyly Camptodactyly is a medical condition that causes one or more fingers or toes to be permanently bent. It involves fixed flexion deformity of the proximal interphalangeal joints. Camptodactyly can be caused by a genetic disorder. In that case, it ...

occur; fingers are short and abnormally bent. These changes in finger shape result in small club shaped appendages. Motion is reduced in all digital joints of the hand.

Genetics

Liebenberg Syndrome follows an

autosomal dominant In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...

mode of inheritance, whereby

heterozygotes Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mo ...

with this mutation express the disease

phenotype In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...

. It is caused by a heterozygous mutation to chromosome 5. It involves the inappropriate enhancement of the PITX1 gene due to genetic deletions and chromosome translocations. PITX1 is a

homeobox gene A homeobox is a DNA sequence, around 180 base pairs long, that regulates large-scale anatomical features in the early stages of embryonic development. For instance, mutations in a homeobox may change large-scale anatomical features of the full-g ...

which are genes that regulate proper body structure development. This PT1X gene encodes a

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The fu ...

expressed in hind limbs. When expressed, it causes the formation of hindlimb structures. Liebenberg Syndrome is a result of one of two different genetic mutations. The first is a deletion upstream of the PITX1 gene on chromosome 5. This deletion includes the H2AFY gene, which is responsible for suppressing an upstream enhancer element known as hs1473. When H2AFY is removed, the enhancer is brought closer to PITX1 and inappropriately enhances it in forelimbs, causing them to adopt hindlimb morphology. The second mutation that can cause the phenotype for Liebenberg syndrome is a translocation of chromosome 18 and chromosome 5. Translocation mutations are ones that switch parts of non-homologous chromosomes with each other. This move introduces two enhancers from chromosome 18 to move to a position directly upstream of PITX1 on chromosome 5. The enhancers increase transcription of the PITX1 gene and cause patients to develop the same phenotype described above.

Diagnosis

Treatment

Surgery is an option to correct some of the morphological changes made by Liebenberg Syndrome. Cases exist where surgery is performed to correct

radial Radial is a geometric term of location which may refer to: Mathematics and Direction * Vector (geometric), a line * Radius, adjective form of * Radial distance, a directional coordinate in a polar coordinate system * Radial set * A bearing f ...

deviations and flexion deformities in the wrist. A surgery called a carpectomy has been performed on a patient whereby a surgeon removes the

proximal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...

row of the

. This procedure removes some of the carpal bones to create a more regular wrist function than is observed in people with this condition.

References

External links

{{Medical resources , DiseasesDB = , ICD10 = , ICD9 = , ICDO = , OMIM = 186550 , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = C566090 Genetic diseases and disorders Syndromes affecting bones