{ "id": "epmc2sa04a", "slug": "langer-mesomelic-dysplasia", "title": "Langer mesomelic dysplasia", "updated": "2026-10-21", "topic_path": [ { "id": "life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/topics/life" }, { "id": "life.health", "label": "Human health and medicine", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health" }, { "id": "life.health.conditions", "label": "Diseases and injuries", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.conditions" }, { "id": "life.health.conditions.structural", "label": "Skin and musculoskeletal conditions", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.conditions.structural" }, { "id": "life.health.conditions.structural.musculoskeletal_conditions", "label": "Musculoskeletal conditions", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.conditions.structural.musculoskeletal_conditions" }, { "id": "life.health.conditions.structural.bone_disease_and_injury", "label": "Bone disease and injury", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.conditions.structural.bone_disease_and_injury" }, { "id": "life.health.conditions.structural.bone_disease_and_injury.acromelic-and-mesomelic-dysplasias", "label": "Acromelic and mesomelic dysplasias", "api_url": "https://www.edgepedia.org/api/v1/topics/life.health.conditions.structural.bone_disease_and_injury.acromelic-and-mesomelic-dysplasias" } ], "geo": [ { "id": "geo.nongeo.nodate.life.health.conditions.structural.bone_disease_and_injury", "label": "Non-geographic · Not dated: Bone disease and injury", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.life.health.conditions.structural.bone_disease_and_injury", "path": [ { "id": "geo.nongeo", "label": "Non-geographic", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo" }, { "id": "geo.nongeo.nodate", "label": "Non-geographic · Not dated", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate" }, { "id": "geo.nongeo.nodate.life", "label": "Life and health", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.life" }, { "id": "geo.nongeo.nodate.life.health", "label": "Human health and medicine", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.life.health" }, { "id": "geo.nongeo.nodate.life.health.conditions", "label": "Diseases and injuries", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.life.health.conditions" }, { "id": "geo.nongeo.nodate.life.health.conditions.structural", "label": "Skin and musculoskeletal conditions", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.life.health.conditions.structural" }, { "id": "geo.nongeo.nodate.life.health.conditions.structural.musculoskeletal_conditions", "label": "Musculoskeletal conditions", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.life.health.conditions.structural.musculoskeletal_conditions" }, { "id": "geo.nongeo.nodate.life.health.conditions.structural.bone_disease_and_injury", "label": "Bone disease and injury", "api_url": "https://www.edgepedia.org/api/v1/geo/geo.nongeo.nodate.life.health.conditions.structural.bone_disease_and_injury" } ] } ], "excerpt": "Langer mesomelic dysplasia (LMD) is a rare inherited bone growth disorder causing severe short stature and shortened arms and legs, from missing both copies of the SHOX gene.", "snippet": "Langer mesomelic dysplasia (LMD) is a rare inherited bone growth disorder causing severe short stature and shortened arms and legs, from missing both copies of the SHOX gene.", "node": "life.health.conditions.structural.bone_disease_and_injury.acromelic-and-mesomelic-dysplasias", "markdown": "# Langer mesomelic dysplasia\n\n**Langer mesomelic dysplasia** (LMD) is an uncommon inherited bone growth disorder in which both working copies of the [SHOX](https://www.edgepedia.org/shox) gene are missing, producing markedly disproportionate short stature along with mesomelic and rhizomelic shortening affecting both the arms and the legs[1](https://www.orpha.net/en/disease/detail/2632). It is the homozygous or compound heterozygous, more severe counterpart of [Léri-Weill dyschondrosteosis](https://www.edgepedia.org/leri-weill-dyschondrosteosis), in which only one SHOX copy is affected[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/). The condition is present before birth (antenatal onset) and is listed as OMIM 249700 and ORPHA:2632[1](https://www.orpha.net/en/disease/detail/2632).\n\n| Key fact | Detail |\n|---|---|\n| Definition | Rare genetic skeletal dysplasia with severe disproportionate short stature and mesomelic and rhizomelic limb shortening[1](https://www.orpha.net/en/disease/detail/2632) |\n| Cause | Biallelic (homozygous or compound heterozygous) pathogenic SHOX variants producing SHOX nullizygosity[3](https://www.ncbi.nlm.nih.gov/sites/books/NBK279130/) |\n| Inheritance | Pseudoautosomal recessive; SHOX lies in the pseudoautosomal region present on both the X and Y chromosomes[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/) |\n| Prevalence | Point prevalence below 1 in 1,000,000; Orphanet records more than 100 described cases, while a 2026 review counts fewer than one hundred[1](https://www.orpha.net/en/disease/detail/2632) • [4](https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1876732/full) |\n| Height | Final adult heights reported between −4.2 and −8.9 SDS in a series of 15 cases[3](https://www.ncbi.nlm.nih.gov/sites/books/NBK279130/) |\n| Age of onset | Antenatal[1](https://www.orpha.net/en/disease/detail/2632) |\n| Prognosis | Cognitive development and life expectancy are generally preserved[4](https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1876732/full) |\n\n## Clinical features\n\nAffected individuals have extreme shortening of the long bones of the arms and legs (mesomelia), producing very short stature[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/). The ulna in the forearm and the fibula in the lower leg are often underdeveloped or absent, while the radius and tibia are unusually short, thick, and curved[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/). The Orphanet clinical description also lists a malformed humeral head, a radially bowed shaft, distorted carpal bones, a shortened femoral neck, and a proximal fibular half that is either missing or underdeveloped[5](https://www.orpha.net/en/disease/detail/2632?mode=name&search=).\n\nThe disorder presents at birth with severely shortened long bones involving both the middle and proximal limb segments[5](https://www.orpha.net/en/disease/detail/2632?mode=name&search=). Additional features include hypoplasia of the mandible and micrognathia, short fingers, and broad hands[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/) • [6](https://pmc.ncbi.nlm.nih.gov/articles/PMC1180673/). [Madelung deformity](https://www.edgepedia.org/madelung-deformity), a wrist and forearm abnormality, is typically not part of LMD according to the Endotext skeletal dysplasias chapter[3](https://www.ncbi.nlm.nih.gov/sites/books/NBK279130/), although MedlinePlus states that some affected individuals do have it, where it may cause pain and limit wrist movement[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/). Orphanet lists Madelung deformity among the very frequent clinical signs[7](https://www.orpha.net/en/disease/sign/2632).\n\nGrowth failure is severe. A series described by Fukami and colleagues reported 15 cases of LMD with final adult heights ranging from −4.2 to −8.9 SDS, meaning between 4.2 and 8.9 standard deviations below the population mean for age[3](https://www.ncbi.nlm.nih.gov/sites/books/NBK279130/). An earlier review gave a height range of −5.5 to −8.9 SDS[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC4971310/).\n\n## The SHOX gene and mechanism\n\nLMD results from changes involving the SHOX (short stature homeobox) gene, which lies in the pseudoautosomal region 1 (PAR1) at Xp22.33/Yp11.32[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/) • [9](https://pmc.ncbi.nlm.nih.gov/articles/PMC3400739/). The SHOX protein is a homeodomain-containing transcription factor important for chondrocyte proliferation, differentiation, and growth plate organization, and it is particularly important for the growth and maturation of the limb bones[4](https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1876732/full) • [2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/).\n\nThe most common cause is a deletion of the entire SHOX gene; other causes include mutations within the gene and deletions of nearby regulatory material that normally controls its activity[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/). Across SHOX-related disorders, deletions of the gene or its downstream enhancers account for about 90% of identified mutations[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC3400739/). All of these changes greatly reduce or eliminate SHOX protein production, and this lack of protein disrupts normal bone development[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/).\n\n## Inheritance and family risk\n\nBecause SHOX sits in the pseudoautosomal region, it is present on both sex chromosomes, so both females (two X chromosomes) and males (one X and one Y) normally carry two functional copies[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/). The disorder follows a pseudoautosomal recessive pattern: in females both X-chromosome copies must be missing or altered, and in males both the X and the Y copy must be affected[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/).\n\nHeterozygous carriers, who have one affected copy, instead show Léri-Weill dyschondrosteosis, a similar but typically less severe disorder marked by short stature, mesomelia, and Madelung deformity of the forearm[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/) • [6](https://pmc.ncbi.nlm.nih.gov/articles/PMC1180673/). Several couples in which both members have Léri-Weill dyschondrosteosis have had children with LMD[8](https://pmc.ncbi.nlm.nih.gov/articles/PMC4971310/). GeneReviews quantifies the risk when both parents have SHOX deficiency: each offspring has a 50% chance of having a SHOX deficiency disorder, a 25% chance of having the Langer type of mesomelic dwarfism, and a 25% chance of having neither condition[10](https://www.ncbi.nlm.nih.gov/books/NBK1215/pdf/Bookshelf_NBK1215.pdf).\n\n## Diagnosis and frequency\n\nDiagnosis can be established from clinical and X-ray features, including mesomelic disproportion of the limbs; genetic testing confirms the clinical diagnosis and supports prognosis and counseling[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC3400739/). Prenatal diagnosis is technically feasible and, among the SHOX-related conditions, is recommended only for LMD[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC3400739/).\n\nThe exact prevalence is unknown. Orphanet gives a point prevalence below 1 in 1,000,000 and states that more than 100 cases have been described, most from populations with a high level of consanguinity[1](https://www.orpha.net/en/disease/detail/2632) • [5](https://www.orpha.net/en/disease/detail/2632?mode=name&search=). MedlinePlus reports that several dozen affected individuals have appeared in the scientific literature[2](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/), and a 2026 narrative review by Piwar and colleagues counts fewer than one hundred documented cases[4](https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1876732/full). LMD has a higher prevalence in populations with a high incidence of consanguinity[9](https://pmc.ncbi.nlm.nih.gov/articles/PMC3400739/).\n\n## History\n\nLeonard Langer first described the condition in 1967, and it was later shown to result from homozygous loss of SHOX[3](https://www.ncbi.nlm.nih.gov/sites/books/NBK279130/). The molecular link was established in 1998, when Belin and colleagues showed large-scale SHOX deletions and a nonsense mutation in families with dyschondrosteosis and demonstrated that Langer mesomelic dwarfism results from homozygous mutations at the same locus[11](https://www.nature.com/articles/ng0598-67). Early molecular confirmation came from affected fetuses: a 24-week fetus with a 45,X karyotype and a SHOX-encompassing microdeletion on its single [X chromosome](https://www.edgepedia.org/x-chromosome) was nullizygous for SHOX, and other fetuses carried deletions inherited from both parents[12](https://pmc.ncbi.nlm.nih.gov/articles/PMC13436952/).\n\n## References\n\n1. [Langer mesomelic dysplasia, Orphanet ORPHA:2632](https://www.orpha.net/en/disease/detail/2632)\n2. [Langer mesomelic dysplasia, MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/langer-mesomelic-dysplasia/)\n3. [Skeletal Dysplasias, Endotext, NCBI Bookshelf](https://www.ncbi.nlm.nih.gov/sites/books/NBK279130/)\n4. [Piwar H, Pawlasek J, Sielaff P, Sztachelska M, Ordak M (2026). Langer mesomelic dysplasia as a rare manifestation of SHOX deficiency: a narrative review. Frontiers in Genetics 17:1876732](https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2026.1876732/full)\n5. [Orphanet disease detail: Langer mesomelic dysplasia (clinical description)](https://www.orpha.net/en/disease/detail/2632?mode=name&search=)\n6. [Genetic Disorders of the Skeleton: A Developmental Approach, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC1180673/)\n7. [Orphanet clinical signs and symptoms, ORPHA:2632](https://www.orpha.net/en/disease/sign/2632)\n8. [A Track Record on SHOX: From Basic Research to Complex Models and Therapy, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC4971310/)\n9. [Clinical utility gene card for: Leri-Weill dyschondrosteosis (LWD) and Langer mesomelic dysplasia (LMD), PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC3400739/)\n10. [SHOX Deficiency Disorders, GeneReviews, NCBI Bookshelf PDF](https://www.ncbi.nlm.nih.gov/books/NBK1215/pdf/Bookshelf_NBK1215.pdf)\n11. [Belin V et al. (1998). SHOX mutations in dyschondrosteosis (Leri-Weill syndrome). Nature Genetics 19:67–69](https://www.nature.com/articles/ng0598-67)\n12. [Langer mesomelic dysplasia as a rare manifestation of SHOX deficiency: a narrative review, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC13436952/)\n\n---\n*Topic: Encyclopedia › Life and health › Human health and medicine › Diseases and injuries › Skin and musculoskeletal conditions › Musculoskeletal conditions › Bone disease and injury › Acromelic and mesomelic dysplasias*\n\n*Initially written Oct 21, 2026*\n\n*Copyright 2026 EdgeChat AI, a subsidiary of Biostate AI.*\n\nLicense: Edgepedia Community License 1.0, https://www.edgepedia.org/edgepedia/license\n", "same_as": [], "url": "https://www.edgepedia.org/langer-mesomelic-dysplasia", "markdown_url": "https://www.edgepedia.org/langer-mesomelic-dysplasia.md", "license": { "name": "Edgepedia Community License 1.0", "url": "https://www.edgepedia.org/edgepedia/license", "summary": "Free with credit, commercial use included. AI training is open to everyone. For other uses, organizations over USD 100M in revenue or 100M monthly users license separately.", "spdx": "LicenseRef-Edgepedia-Community-1.0" }, "credit": "\"Langer mesomelic dysplasia\", Edgepedia (EdgeChat), https://www.edgepedia.org/langer-mesomelic-dysplasia. Edgepedia Community License 1.0.", "credit_md": "\"[Langer mesomelic dysplasia](https://www.edgepedia.org/langer-mesomelic-dysplasia)\", Edgepedia (EdgeChat), [https://www.edgepedia.org/langer-mesomelic-dysplasia](https://www.edgepedia.org/langer-mesomelic-dysplasia). [Edgepedia Community License 1.0](https://www.edgepedia.org/edgepedia/license).", "credit_html": "\"Langer mesomelic dysplasia\", Edgepedia (EdgeChat), https://www.edgepedia.org/langer-mesomelic-dysplasia. Edgepedia Community License 1.0.", "speakable": "Langer mesomelic dysplasia is a rare inherited bone growth disorder causing severe short stature and shortened arms and legs, from missing both copies of the SHOX gene." }