Myhre Syndrome

Disease Overview

Summary

Myhre syndrome is a rare but increasingly diagnosed genetic disorder with a broad set of observable characteristics (phenotype) including short stature, characteristic facial features, distinctive heart and aorta problems, mild to moderate intellectual disability, autism/autistic-like behavior, and various bone and joint abnormalities. All of these features are highly variable and influenced by the gene variant (see below) the person has and their age. The familiar facial features are often mild in very young children, but present in almost all individuals. These include a small narrow eye opening (short palpebral fissure), flat facial profile (maxillary hypoplasia), prominent jaw (which becomes apparent with age) and a relatively prominent nose. Other findings include hearing impairment, short fingers and toes (brachydactyly), muscles that appear abnormally firm (muscular pseudohypertrophy), joint stiffness, and narrowing (stenosis) of the upper airway, voice box (larynx) and windpipe (trachea). Abnormalities of the heart structure (congenital heart defects), heart muscle (cardiomyopathy) and pericardium are common and distinctive. A risk for certain types of cancer is recognized.

Myhre syndrome is caused by changes (pathogenic variants) in the SMAD4 gene. It was thought that all people with a disease-causing SMAD4 variant had a new (de novo) variant that occurred around the time of conception and was not inherited from a parent. However, it is increasingly recognized that Myhre syndrome can be inherited from a parent. A person with Myhre syndrome has a 50% chance of passing the gene variant to each child.

In addition to case reports and small series of cases reported in the medical literature, there are 3 large studies focusing on how this syndrome progresses over time (natural history) (Yang et al., 2022; Lin et al., 2024, Vanbelleghem et al., 2024) and characteristics of adults with Myhre syndrome (Vanbelleghem et al., 2024). A state-of-the-art review of the literature is now available (Brand et al., 2025).

Introduction

Myhre syndrome was first described in two unrelated males in 1981 by Drs. Myhre, Ruvalcaba and Graham. In 1998, the first of a series of papers reported on a similar condition consisting of (L)aryngotracheal stenosis (A)rthropathy, (P)rognathism, (S)hort stature syndrome (LAPS), that was recognized to be the same as Myhre syndrome (Hopkins et al., 1998; Lindor et al., 2002, 2009 and 2012). It was proven that both disorders had the same variant in the same gene (SMAD4). This was viewed as a different expression (phenotypic variation) of the same disorder. Part of the variable expression of Myhre syndrome is related to the age of diagnosis. Of the five variants in SMAD4 known to cause Myhre syndrome, it is not yet known whether there are correlations between the specific variant and clinical features. The historical evolution of the clinical and genetic features of Myhre syndrome was surveyed in Brand et al.,2025.

• View Full Report Show Less
• Print / Download as PDF

• Next section >

• < Previous section
• Next section >

Synonyms

• laryngotracheal stenosis, arthropathy, prognathism, and short stature
• LAPS Syndrome

• < Previous section
• Next section >

• < Previous section
• Next section >

Signs & Symptoms

Although researchers have been able to describe a recognizable syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified patients and the lack of large clinical studies of this ultra-rare syndrome prevent physicians from developing a complete picture of associated symptoms and prognosis. However, Myhre syndrome centers in the United States (mainly MGB for Children in Boston) and Europe (mainly in Ghent, Paris and Naples) are steadily contributing to the knowledge base for patients and healthcare providers.

• No other genes besides SMAD4 have been identified to cause Myhre syndrome and all patients require genetic testing to exclude patients who are “like Myhre syndrome”. Therefore, it is important to note that affected individuals may not have all the symptoms discussed below and that every patient is unique. Parents of affected children and adults with Myhre syndrome should talk to their primary care physician and medical team about their specific case, associated symptoms and overall prognosis.
• Growth deficiency is a common finding and usually occurs before birth (prenatally), often resulting in low birth weight. Growth deficiencies continue after birth and most children are shorter than would be expected for age (short stature) except for many children with the SMAD4 Arg496Cys variant.
• Puberty has occurred early in some patients, while in a few it has been delayed. Affected females may experience irregular menstruation, or early-onset heavy menstruation (menometrorhagia). Affected males may experience failure of the testes to descend into the scrotum (cryptorchidism). Some have premature puberty and when present, has not been associated with a pituitary tumor.
• Most affected infants and children have distinctive facial features including relatively larger head circumference (macrocephaly), eyes which are small and narrow (short palpebral fissure), underdeveloped midfacial structures (maxillary hypoplasia), prominent nose, short philtrum, small mouth, thin lips, and small ears. The prominent jaw seen in older children and adults is related to the underdeveloped midface (disharmonic facial growth) rather than overgrowth of the jaw (prognathism).
• The most common obstruction to breathing is a restricted, stiff chest (thorax). This is part of the spectrum of stiff joints in Myhre syndrome.
• The airway itself can be affected at various levels such as narrowing or blockage of the nasal passage, especially the back of the nose (choanal atresia).
• In a small number of patients, progressive narrowing of the larynx and trachea was seen, a condition known as laryngotracheal stenosis. This results in noisy breathing (stridor), a loud cough (resembling croup) and respiratory insufficiency sometimes requiring oxygen or breathing tubes (tracheostomy). Without treatment, laryngotracheal stenosis can be life-threatening. The cause has not been proven, but its appearance in a newborn supports the hypothesis that there is a developmental component. It has not appeared after a tube has been inserted into the windpipe(intubation) one time and many patients have had many intubations without developing stenosis. The risk for this condition appears to increase with age and it usually presents in adolescence or young adulthood. Because of the narrow trachea, the lungs may be unable to take in enough air for the affected person to breathe properly (pulmonary insufficiency). In addition to restriction from the stiff thorax, there can be obstructive lung disease, often asthma. disorders of. Interstitial lung disease leads to shortness of breath and coughing.
• Most individuals with Myhre syndrome develop hearing loss. In some, it is due to the accumulation of wax-like material or from recurrent ear infections. This prevents sound waves from being conducted through the middle ear (conductive hearing loss). Other individuals may have hearing loss due to an impaired ability of the auditory nerves to transmit sensory input from the ears to the brain (sensorineural hearing loss). A few patients have abnormal inner ear structures (dysplasia) which are detected by a CT scan of the temporal region. Hearing loss can also be mixed, which means individuals have a combination of conductive and sensorineural hearing loss. Most patients have either conductive or mixed. Hearing loss usually affects both ears (bilateral), although the degree of severity varies from one person to another.
• Narrowing of the tear ducts (nasolacrimal duct stenosis) may not be diagnosed as such. Instead, there may be persistent tearing or puffiness of the eyes.
• Developmental delays occur in nearly all people with Myhre syndrome. Mild to moderate intellectual disability occurs in most people, although an increasing number of higher functioning people have been identified.
• Behavioral abnormalities including difficulties with social interactions, poor communication skills, hyperactivity, stubbornness, and/or repetitive behaviors are common. Many patients are considered to be on the autism spectrum.
• Several skeletal abnormalities have been described in individuals with Myhre syndrome but do not impact health. Bones of the skull (calvaria) may be abnormally thick which does not harm a person. The ribs may be abnormally broad and wide, and the upper portions of the hip bone may be underdeveloped (hypoplastic iliac wings). The long bones of the body (i.e., those in the arms and legs) may be unusually narrow, round (tubular) and short. The fingers and toes may be short (brachydactyly). Webbing (syndactyly) of the hands and feet, fifth fingers that are curved inward (clinodactyly), and fingers which are stiff and contracted (camptodactyly) are also common findings.
• Stiff joints of small and large bones are common. Contractures are less frequent. Over time, mobility is limited.
• In early childhood, the muscles of the arms and legs may feel firm and look larger creating a muscular appearance (muscular pseudohypertrophy) However, this is not accompanied by greater strength.
• Progressive stiffening or thickening of the skin may also be noticeable and is quite common. Abnormal scars include small, thin white scars, others which are thick (hypertrophic).
• Affected individuals may have an increased susceptibility to infections of the ears, sinuses and lungs (sinopulmonary). Narrowing of the airways and the anatomy of the ear may predispose individuals to sinus and ear infections.
• Most people with Myhre syndrome have at least one problem involving the heart or aorta. These can be very mild or occasionally severe. Congenital heart defects are structural problems that are usually present at birth. Later in life there can be pericardial disease (the lining of the heart) which may begin as a collection of fluid (pericardial effusion). In some people, it may progress to thickening, or inflammation. Pericarditis can be recurrent and cause life-threatening complications. When the heart has an effusion, there may also be pleural effusion (fluid buildup in the chest cavity outside of the lungs).
• The aorta in Myhre syndrome can have areas of narrowing which can be present in a specific location (stenosis, coarctation) or diffusely mild (hypoplasia).
• High blood pressure (hypertension) can result from aorta obstruction.
• Less common signs and symptoms in Myhre syndrome include facial anomalies such as cleft palate or cleft lip. There can be drooping of the upper eyelids (ptosis) or blockage of a tear duct (nasolacrimal duct stenosis).
• Intestinal problems include chronic constipation, which is common, and can lead to an inability to be toilet trained. Rare problems involve obstruction of the duodenum, pylorus and rectum.
• Kidney (renal) abnormalities include absence (agenesis) of a kidney or obstruction (hydronephrosis).
• Eye (ophthalmologic) abnormalities are common and include refraction abnormalities such as an inability to focus on objects which are close (hypermetropia or farsightedness) or an imperfection in the curvature of the eye leading to blurred vision (astigmatism); less often, there can be crossing of the eyes (strabismus) or cataracts at a young age. Rarely, the optic nerves at the back of the eye can appear enlarged (pseudopapilledema).

• < Previous section
• Next section >

• < Previous section
• Next section >

Causes

Myhre syndrome is caused by a gain-of-function disease-causing pathogenic) variants in the SMAD4 gene. It is the only gene known to cause the disorder.

Genes provide instructions for creating (encoding) proteins that play a critical role in many functions of the body. When a variant occurs, the protein product of the gene may be faulty, inefficient, or absent. Depending upon the functions of the protein, this can affect many organ systems of the body, including the brain. In Myhre syndrome, the variants are called “missense” which are small changes in the gene that can affect how the protein product works.

The SMAD4 gene contains instructions for creating (encoding) a protein that is expressed throughout the developing fetus and in most adult tissue and cell types. Variants in the SMAD4 gene lead to insufficient levels of working (functional/normal) copies of the protein. Because this protein is expressed throughout the body (ubiquitously), this accounts for the widespread and varied symptoms that are potentially associated with Myhre syndrome.

Until recently, all reported variants have occurred as new (sporadic or de novo) variants, which means that in these patients, the gene variant occurred at the time of the formation of the egg or sperm for that child only, and no other family member will be affected. Since publication of a family from Belgium with an affected mother and two affected children (Meerschaut et al., 2019), there have been several additional duos (parent and child). We know now that an affected individual (at least with the variant in the reported family) could potentially pass on a gene variant that causes Myhre syndrome in an autosomal dominant manner.

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.

The association of advanced paternal age in Myhre syndrome has been noted. Research has shown that de novo variants occurred in the sperm before conception in some people with Myhre syndrome (Wood et al., 2024).

• < Previous section
• Next section >

• < Previous section
• Next section >

Affected populations

Myhre syndrome is an extremely rare inherited disorder that, affects males and females in nearly equal numbers. Almost 200 patients have been reported in the medical literature, and cases are being steadily published. Because some people with Myhre syndrome most likely go undiagnosed or misdiagnosed, determining the true frequency of the disorder in the general population is difficult. There is general agreement that the rate of new diagnoses in both the young and adults will increase.

• < Previous section
• Next section >

• < Previous section
• Next section >

Disorders with Similar Symptoms

Symptoms of the following disorders can be similar to those of Myhre syndrome. Comparisons may be useful for a differential diagnosis but with the additional experience of the past decade, some of these syndromes are no longer considered.

Other congenital disorders that may be characterized by intellectual disability and growth deficiency occurring in association with facial differences, skeletal malformations, and/or other physical abnormalities similar to those associated with Myhre syndrome include, but are not limited to acromicric dysplasia, geleophysic dysplasia, Weill-Marchesani syndrome and acromesomelic dysplasia. None of these syndromes is identical to Myhre syndrome. The thickened skin associated with Myhre syndrome may resemble the stiffened skin seen in stiff skin syndrome or juvenile scleroderma.

• < Previous section
• Next section >

• < Previous section
• Next section >

Diagnosis

A provisional clinical diagnosis of Myhre syndrome is usually made based on a thorough clinical evaluation, identification of characteristic physical findings, a detailed patient history and/or specialized test (particularly advanced imaging techniques). Molecular genetic testing that identifies a disease-causing variant in SMAD4 confirms the diagnosis.

Molecular genetic testing is rarely done as a targeted gene analysis (for SMAD4). Currently, testing is performed as either whole exome sequencing (WES) or increasingly, as part of whole genome sequencing (WGS) analysis. The use of a panel of genes related to skeletal dysplasia, intellectual disability and/or autism, hearing loss, or cancer has also been successful for the diagnosis of Myhre syndrome (Lin et al., 2024).

Developmental delays which typically present in some form in infancy and into the toddler years persist. Intellectual disability may not be detected until the child is in school and old enough to participate in clinical testing. Clinical evaluation, ideally a neuropsychologic evaluation, should be conducted early in development when there is a concern. Ideally, this testing is repeated on a continuing basis to help determine the presence and extent of certain findings such as intellectual disability and behavioral issues which are on the autism spectrum. Such evaluations can help ensure that appropriate steps are taken to help affected individuals reach their potential. It is important to emphasize that the vast majority of people living with Myhre syndrome are active and engaged in social activities but rarely live independently. They can make progress living with their challenges. A small number of adults have married, others have jobs.

Characteristic facial features, and/or heart defects may also be present at birth. X-ray testing (skeletal survey) may be used to identify skeletal malformations which are usually mild. A baseline echocardiogram and complete cardiology consultation is essential for all patients at the time of diagnosis and may help to determine the exact nature of heart defects. This should be repeated on a regular basis (every 1-2 years) since some features can progress, but the exact schedule is determined by the cardiologist.

Prenatal (fetal) diagnosis has been reported (Hui et al., 2023; Jury et al., 2024) and may occur more frequently with expansion of fetal genetic sequencing. Increased awareness of imaging features (growth retardation, structural heart defects) may also lead to fetal testing.

Growth delay, abnormally stiff joints and hearing impairment may not become obvious until late infancy or early childhood. Periodic testing of an infant’s or child’s hearing is essential to detect any loss in hearing capability.

• < Previous section
• Next section >

• < Previous section
• Next section >

Standard Therapies

Treatment
The treatment of Myhre syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment requires the coordinated efforts of a team of specialists. Pediatricians are key to providing standard health maintenance (including vaccinations). Primary care providers need the insights of specialists. These include orthopedic specialists and rheumatologists who treat skeletal and joint problems, cardiologists who diagnose and treat disorders of the heart, otolaryngologists and pulmonologists who assess and treat ear, nose, airway and lung disorders, audiologists who assess and treat hearing problems, ophthalmologists who assess and treat eye disorders. Other specialists may be needed for skin problems (dermatologists), puberty issues (endocrinologists) and kidney problems (nephrologists). To evaluate and treat problems related to development, behavior and school, neuropsychologists, speech pathologists, physical therapists and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment.

Genetic counseling is recommended for affected individuals and their families. With the awareness of familial occurrence (Myhre syndrome in a parent and child), a parent may be offered prenatal or preconception diagnosis. (submitted, Brand et al., July 2/2025)

A care coordinator should assist the primary care physician, a role which is often performed by the medical geneticist.

Since individuals with Myhre syndrome are susceptible to the development of excessive scar tissue (fibrosis) related to tissue injury which might be related to surgery, the team of anesthesia, surgery and healthcare providers in the intensive care unit (ICU) should review the surgical plan. Efforts should be made to avoid anything but the most necessary of invasive interventions, including endoscopic procedures. As needed, anesthesiologists should use the smallest sized endotracheal tube. Post-intubation care should be provided.

There are no standardized treatment protocols or evidence-based guidelines for affected individuals. The most comprehensive recommendations (Lin et al, 2024) provide pragmatic guidance. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with Myhre syndrome.

Certain abnormalities (e.g., small mouth with narrow palate, syndactyly, congenital heart defects, cleft palate or lip, duodenal atresia, pyloric stenosis, and/or cryptorchidism) may require surgery. Affected infants should be evaluated for choanal atresia which can be repaired by surgery and has led to improved feeding. Other conditions that can be treated surgically include scoliosis, congenital cataracts and hypospadias.

Laryngotracheal stenosis may require surgical treatment; however, the condition may recur after successful treatment. In people who require a tube to be inserted into the windpipe (intubation) to assist breathing (as might be needed when undergoing anesthesia), special care must be taken because of the risk leading to laryngotracheal stenosis. Ultimately, patients may require a tracheostomy in which a tube is surgically implanted through a cut in the throat to allow direct access to the windpipe.

Some individuals with Myhre syndrome may have difficulty swallowing and/or feeding. In some patients, this may necessitate placing a tube through a small insertion in the abdominal wall and directly into the stomach (gastrostomy tube).

It is not known if there is a specific immune deficiency in Myhre syndrome. As indicated, appropriate immunologic tests should be conducted with consultation from an immunologist.

Early intervention is important to ensure that children with Myhre syndrome reach their potential. Special services that may be beneficial include special remedial education, special social support, physical therapy, and other medical, social, and/or vocational services. Long-term follow up and regular clinical evaluation of affected individuals is required to detect specific symptoms or complications potentially associated with Myhre syndrome. Applied Behavioral Analysis (ABA) has been reported by healthcare providers and families to be of great help, although this has not been formally studied. If possible, it should be included.

Females who have early onset puberty and menstruation, and those who had heavy, painful periods, should be evaluated by a gynecologist. Although endometrial cancer and some forms of brain tumor have been reported, cancer remains a rare event and surveillance has not been addressed. Affected females have specific requirements for follow up because of abnormalities involving the beginning of puberty and possible early development of menopause.

• < Previous section
• Next section >

• < Previous section
• Next section >

Clinical Trials and Studies

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. As of 2025, there are no clinical trials for Myhre syndrome.

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, contact:
www.centerwatch.com

For more information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

• < Previous section
• Next section >

• < Previous section
• Next section >

Resources

(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., short stature, intellectual disability, etc.].)

• < Previous section
• Next section >

• < Previous section
• Next section >

References

JOURNAL ARTICLES

Brand MR, Monsberger R, Hopkin RJ, Lin AE. Research Review of Myhre Syndrome. Am J Med Genet C Semin Med Genet. Published online June 6, 2025. doi:10.1002/ajmg.c.32145

Lindsay ME, Scimone ER, Lawton J, et al. Gain-of-function variants in SMAD4 compromise respiratory epithelial function. J Allergy Clin Immunol. 2025;155(1):107-119.e2. doi:10.1016/j.jaci.2024.08.024

Jury J, Joubert M, Le Vaillant C, et al. Prenatal Diagnosis of Myhre Syndrome in Two Cases: Further Delineation of the Cardiac and External Phenotype. Prenat Diagn. 2024;44(10):1268-1272. doi:10.1002/pd.6642

Lin AE, Scimone ER, Thom RP, et al. Emergence of the natural history of Myhre syndrome: 47 patients evaluated in the Massachusetts General Hospital Myhre Syndrome Clinic (2016-2023). Am J Med Genet A. 2024;194(10):e63638. doi:10.1002/ajmg.a.63638

Vanbelleghem E, Van Damme T, Beyens A, et al. Myhre syndrome in adulthood: clinical variability and emerging genotype-phenotype correlations [published correction appears in Eur J Hum Genet. 2024 Sep 10. doi: 10.1038/s41431-024-01690-z.]. Eur J Hum Genet. 2024;32(9):1086-1094. doi:10.1038/s41431-024-01664-1

Wears K, Lin AE, Starr LJ. The Myhre Syndrome Foundation as a global modern support group: The business of rare. Am J Med Genet C Semin Med Genet. 2024;196(4):e32104. doi:10.1002/ajmg.c.32104

Wood KA, Tong RS, Motta M, et al. SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline. Am J Hum Genet. 2024;111(9):1953-1969. doi:10.1016/j.ajhg.2024.07.006

Hui PW, Mok YK, Luk HM, et al. Prenatal diagnosis of Myhre syndrome with a heterozygous pathogenic variant in SMAD4 gene presented with thick nuchal translucency and cardiac abnormalities. Prenat Diagn. 2023;43(10):1366-1369. doi:10.1002/pd.6414

Cappuccio G, Brunetti-Pierri N, Clift P, et al. Expanded cardiovascular phenotype of Myhre syndrome includes tetralogy of Fallot suggesting a role for SMAD4 in human neural crest defects. Am J Med Genet A. 2022;188(5):1384-1395. doi:10.1002/ajmg.a.62645

Starr LJ, Lindsay ME, Perry D, et al. Review of the Pathologic Characteristics in Myhre Syndrome: Gain-of-Function Pathogenic Variants in SMAD4 cause a Multisystem Fibroproliferative Response. Pediatr Dev Pathol. 2022;25(6):611-623. doi:10.1177/10935266221079569

Yang DD, Rio M, Michot C, et al. Natural history of Myhre syndrome. Orphanet J Rare Dis. 2022;17(1):304. Published 2022 Jul 30. doi:10.1186/s13023-022-02447-x

Jeon MJ, Kim MJ, Kim JH, et al. Multilevel Airway Stenosis Being Bypassed by a Customized Tracheostomy Tube in an Infant with Myhre Syndrome. Pediatr Allergy Immunol Pulmonol. 2021;34(2):83-87. doi:10.1089/ped.2021.0029

Lin AE, Alali A, Starr LJ, et al. Gain-of-function pathogenic variants in SMAD4 are associated with neoplasia in Myhre syndrome [published correction appears in Am J Med Genet A. 2024 Jun;194(6):e63497. doi: 10.1002/ajmg.a.63497.]. Am J Med Genet A. 2020;182(2):328-337. doi:10.1002/ajmg.a.61430

Meerschaut I, et al. Myhre syndrome: A first familial recurrence and broadening of the phenotypic spectrum. Am J Med Genet. 2019; 179A: 2494–2499.

Lin AE, et al. Gain-of-function mutations in SMAD4 cause a distinctive repertoire of cardiovascular phenotypes in patients with Myhre syndrome. Am J Med Genet. 2016; 170A: 2617-2631.

Starr LJ, et al. Myhre syndrome: clinical features and restrictive cardiopulmonary complications. Am J Med Genet. 2015; 167A: 2893-2901.

Le Goff C, Michot C, Cormier-Daire V. Myhre syndrome. Clin Genet. 2014;85:503-513.

Michot C, Le Goff C, Mahaut C, et al. Myhre and LAPS syndromes: clinical and molecular review of 32 patients. Eur J Hum Genet. 2014;22:1272-1277.

Picco P, Naselli A, Pala G, et al. Recurrent pericarditis in Myhre syndrome. Am J Med Genet A. 2013;161A:1164-1166.

Caputo V, et al. A restricted spectrum of mutations in the SMAD4 tumor-suppressor gene underlies Myhre syndrome. Am J Hum Genet. 2012; 90:161-169.

Lindor NM, et al. Mutations of SMAD4 account for both LAPS and Myhre syndromes. Am J Med Genet. 2012;158A: 1520-1521.

Le Goff C, Mahaut C, Abhyankar A, et al. Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nat Genet. 2011;44:85-88.

Lindor NM, et al. Confirmation of Existence of a New Syndrome: LAPS Syndrome. Am J Med Genet. 2002;109 93-99.

Lindor NM, et al. LAPS Syndrome and Myhre Syndrome: Two Disorders or One? Am J Med Genet. 2009; 149A:798-799.

Hopkin RJ, Cotton R, Langer LO, Saal HM. Progressive laryngotracheal stenosis with short stature and arthropathy. Am J Med Genet. 1998;80:241-246.

Myhre SA, et al. A new growth deficiency syndrome. Clin Genet.1981; 20:1-5.

INTERNET

Lin AE, Brunetti-Pierri N, Lindsay ME, Schimmenti LA, Starr LJ. Myhre Syndrome. 2017 Apr 13 [updated 2024 Dec 12]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025. PMID: 28406602. Accessed July 7, 2025.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:139210; Last Update: 9/25/2024. Available at: https://omim.org/entry/139210. Accessed July 2, 2025.

• < Previous section
• Next section >

• < Previous section

Programs & Resources

• Assistance Programs
• Patient Organizations
• More Information

RareCare^® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

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/

Rare Disease Educational Support 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 NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

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/

Learn more about Patient Assistance Programs >

• < Previous section