- Donate
- Understanding Rare Disease
- Living with a Rare Disease
- Community Support
- Advancing Research
- Driving Policy
- Get Involved
- Rare Disease News
- Resource Library
- About Us
- For Clinicians & Researchers
- For Patient Organizations
Last updated: 9/10/2024
Years published: 1996, 1997, 1998, 2005, 2024
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, for assistance in the preparation of this report.
Summary
Trichorhinophalangeal syndrome type 2 (TRPS2), also known as Langer-Giedion syndrome, is a very rare disorder that affects many organs of the body. It is characterized by intellectual disability, progressive growth delay resulting in short stature, fine, thin hair, unusual facial features (thick eyebrows, especially in the middle, a broad nose with a wide bridge and tip, underdeveloped sides of the nose, a long area between the nose and upper lip, a thin upper lip and ears that stick out), abnormally short fingers and toes (brachydactyly), โcone-shapedโ formation of the โgrowing endsโ of certain bones (epiphyseal coning) and/or development of multiple bony growths (exostoses) projecting outward from the surfaces of various bones of the body.
In addition, some affected people may be unusually flexible (hyperextensible) joints and have diminished muscle tone (hypotonia), excess folds of skin (redundant skin) and/or discolored elevated spots on the skin (maculopapular nevi). Other symptoms may include a very small head (microcephaly), urinary and genital problems, hearing loss (sensorineural deafness) and/or delayed speech development.
The range and severity of symptoms varies greatly from person to person. TRPS2 is due to the absence of genetic material (chromosomal deletions) on chromosome 8. The size of the deletion varies from person to person.
TRPS type 2 is caused by a is due to the absence of a very small piece of genetic material (chromosomal microdeletion) on chromosome 8 (region 8q23.3-q24.11) leading to the loss of the genes TRPS1, RAD21 and EXT1 and is therefore considered a contiguous gene syndrome. The size of the deletion varies from person to person. Usually, the microdeletion occurs the first time in the affected person, but some inherited cases have been reported
Treatment is mainly supportive.
Introduction
In 2023, the classification of genetic skeletal disorders was updated. These updates help to clarify the classification of these related conditions and provide a more accurate understanding of the genetic basis behind them. According to the new guidelines:
Trichorhinophalangeal syndrome type 2 (TRPS2) can vary greatly in its severity and symptoms, even among members of the same family. Reported symptoms may include:
Other physical and developmental features may include:
TRPS2 is caused by the loss of specific genes on a part of chromosome 8. This happens due to a tiny missing piece (called a microdeletion) on chromosome 8 in the region known as 8q23.3-q24.11. The missing genes include TRPS1, RAD21, and EXT1, and because this condition involves the loss of several genes, it is referred to as a โcontiguous gene syndrome.โ
In most cases, this genetic change happens by chance (known as โde novoโ), meaning it is not inherited from either parent. However, in some rare instances, the microdeletion can be passed down from a parent. A few people with TRPS2 have a deletion that affects only the RAD21 and EXT1 genes. These individuals often have facial features that resemble another condition called Cornelia de Lange syndrome.
The TRPS1 gene plays an important role in controlling growth and the development of certain cells, including those involved in forming cartilage and connective tissue around bones.
TRPS2 is inherited in an autosomal dominant pattern. Dominant genetic disorders occur when only a single copy of a disease-causing gene variant is necessary to cause the disease. The gene variant can be inherited from either parent or can be the result of a new (de novo) changed gene in the affected individual that is not inherited. The risk of passing the gene variant from an affected parent to a child is 50% for each pregnancy. The risk is the same for males and females. Usually, the microdeletion occurs de novo, but some inherited cases have been reported.
Since this condition is genetic, it is recommended that affected individuals receive genetic counseling. This counseling helps them understand the chances of passing the condition on to their children and provides support in making informed decisions about family planning.
In almost all reported cases, if someone has a genetic change that causes TRPS2, they will show symptoms of the condition (this is known as 100% penetrance). It is very rare for someone to have a genetic change without showing symptoms (a situation called somatic mosaicism, where there are some cells in the body that do not have the genetic change).
The prevalence of this condition is unknown. Around 100 cases were described in the literature.
Diagnosis is typically suspected on clinical presentation and confirmed by genetic testing through chromosomal microarray analysis identifying the loss of the genetic material on chromosome 8.
Prenatal diagnosis is possible for TRPS2 if the specific variant that causes the condition has already been identified in a family member who is affected. This means that during pregnancy, doctors can test the developing baby to see if they have inherited the same genetic change.
As affected individuals age, specialized imaging techniques (such as various x-ray methods) may be used to identify โcone-shapedโ development of the end portions of certain bones (epiphyseal coning) and/or the formation of numerous bony growths (exostoses) projecting outward from the surfaces of various bones in the body. Intellectual disability, hearing loss and/or speech delays may not be detectable until affected infants grow older.
The management of TRPS2 focuses on addressing specific symptoms and providing supportive care. A team of specialists, including pediatricians, orthopedists, orthopedic surgeons, speech pathologists, audiologists and other healthcare professionals, should work together to create a comprehensive treatment plan tailored to each individualโs needs.
Supportive care may include:
Surveillance should include:
Affected people with impaired mobility should avoid high-impact sports due to the increased risk of injury.
Genetic counseling is recommended for affected individuals and their families to help them understand the condition and its inheritance pattern.
Early intervention, including physical therapy, speech therapy and other supportive measures, is crucial to ensure that children with TRPS2 reach their full potential.
Life expectancy is normal. The reduced mobility and developmental problems can have a major impact on the quality of life.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, in the main, contact: www.centerwatch.com
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Hicks J. Trichorhinophalangeal Syndrome Type II. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:731.
JOURNAL ARTICLES
Dunbar JD, et al., Hip pathology in the trichorhinophalangeal syndrome. J Pediatr Orthop. 1995;15:381-5.
Hou J, et al., A 4-megabase yac contig that spans the Langer-Giedion syndrome region on human chromosome 8q24.1: use in refining the location of the trichorhinophalangeal syndrome and multiple exostoses genes (TRPS1 and EXT1). Genomics. 1995;29:87-97.
Ludecke HJ, et al., Molecular dissection of a contiguous gene syndrome: localization of the genes involved in the Langer-Giedion syndrome. Hum Mol Genet. 1995;4:31-6.
Bauermeister S, et al., The orthopaedic manifestations of the Langer-Giedion syndrome. Orthop Rev. 1992;21:31-5.
INTERNET
TRPS2. Online Mendelian Inheritance in Man (OMIM). Victor A. McKusick, Editor; Johns Hopkins University, Last Edit Date 04/06/2020. https://omim.org/entry/150230 Accessed Sept 10, 2024.
Trichorhinophalangeal syndrome type 2. Orphanet. March 2023. https://www.orpha.net/en/disease/detail/502 Accessed Sept 10, 2024.
Tรผysรผz B, Gรผneล N, Alkaya DU. Trichorhinophalangeal Syndrome. 2017 Apr 20 [Updated 2024 Mar 21]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviewsยฎ [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. Available from: https://www.ncbi.nlm.nih.gov/books/NBK425926/ Accessed Sept 10, 2024.
Trichorhinophalangeal syndrome type 2. MedlinePlus. June 1, 2017. https://medlineplus.gov/genetics/condition/trichorhinophalangeal-syndrome-type-ii/ Accessed Sept 10, 2024.
NORD strives to open new assistance programs as funding allows. If we donโt have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORDโs mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View report
Your donation will help more than 30 million Americans with a rare disease navigate their diagnosis, receive financial assistance, and access the care and support they deserve. Make your tax-deductible gift today!