Última actualización:
August 17, 2020
Años publicados: 1996, 1997, 2001, 2002, 2004, 2007, 2020
NORD gratefully acknowledges Lacie Mehr, MMSc, NORD Editorial Intern from the Emory University Genetic Counseling Training Program and Cecelia A. Bellcross, PhD, MS, CGC, Associate Professor, Director, Genetic Counseling Training Program, Emory University School of Medicine, for assistance in the preparation of this report.
Summary
Meier-Gorlin syndrome (MGS) is a rare genetic disorder. The main features are small ears (microtia), absent or small kneecaps (patellae) and short stature. MGS should be considered in children with at least two of these three features.
There are other features of MGS that may include various skeletal differences, early feeding difficulties and poor weight gain. In addition, unique features of the head and face may be present including a small mouth with full lips, small size of the head (microcephaly) and/or small jaw bones (micrognathia).
People with MGS usually have normal intellectual ability and a normal lifespan.
MGS is usually inherited in an autosomal recessive pattern but can be autosomal dominant in some families.
Introduction
MGS was first reported by Meier in 1959 and Gorlin in 1975. Since then about 67 patients have been described with MGS.
The main clinical features of MGS are small ears, kneecap abnormalities and short stature. These features can be seen at birth and are discussed in more detail below.
People with MGS can have small or absent outer ears (microtia). The ears can also be low-set and/or unusually formed. They may have narrower or absent ear canals which could affect their hearing.
The kneecaps may be small or even missing. This may cause an unstable knee joint which could lead to chronic knee pain.
Short stature is due, in part, to the slow growth that can occur before and after birth in babies with MGS. As a result, these babies have low birth weight and can have feeding difficulties that result in a slower development and short stature.
This syndrome has a range of symptoms with severity anywhere from mild to severe. The following symptoms are associated with MGS, but not everyone diagnosed with MGS will have all of these symptoms.
Skeletal Differences
People with MGS may have differences in their bone development. These may include slender, missing, or unusually shaped ribs with slender arm and leg bones. Elbows can be dislocated, collar bones can be hook-shaped and/or long bones can have flat ends. There have been some patients with an absent or abnormally shallow depression on the upper arm bone located where the bone meets the shoulder. There have also been patients with detachment of cartilage and bone tissue from the surface of a bone, unusually extended joints, and abnormally stiff joints that may lock in position. Specifically, hands can have the fifth finger be abnormally bent, and/or one or more fingers may be permanently flexed.
Facial Features
In addition to those mentioned above, facial features can include a triangular face, an arched roof of the mouth and/or droopy eyelids. Facial features may include full lips and a narrow nose with a small jaw and mouth.
Life Span
Most people with MGS have a normal life expectancy. The oldest documented adult is a 65-year-old woman. The lifespan of those with MGS may depend on the severity of the symptoms experienced by each person.
Intellectual and Motor Development
Most people with MGS have normal intelligence and learning ability. Mental ability and motor coordination is normal or borderline normal. Some affected children show delays in attaining developmental and speech milestones.
Growth
Growth after birth can be delayed during the first year of life with normal growth afterwards. However, due to this delay, people with MGS do not catch up to their peers and tend to be shorter in stature.
Feeding
Feeding problems have been seen in the majority of those with MGS during infancy and young childhood. These problems can be due to acid reflux which may need further medical intervention such as medication.
Respiratory
Likely due to their small stature, people with MGS can have breathing difficulties. Some report problems with releasing the air from their lungs, which will likely need medical intervention. Breathing difficulties can include coughing and wheezing due to weak lung structure. The weak structure and small size of the lungs can lead to recurrent infections in childhood. These infections tend to disappear after childhood.
Sexual Development
In some boys with MGS, the testes may not descend into the scrotum (undescended testes). Some boys have an abnormal location of the urinary opening on the underside of the penis (hypospadias). Both of these concerns can be treated with surgery.
Some girls with MGS may have underdeveloped breasts after reaching puberty. Some women with MGS have a small uterus. Some women with MGS have been reported to have many cysts on their ovaries. The impact of MGS on pregnancy is not well understood. However, there is a documented case of a woman with MGS having successful pregnancies, though the babies were born premature.
Both males and females with MGS tend to have sparse or absent underarm hair while pubic hair growth is normal.
MGS can be caused by changes (mutations) in eight different genes (ORC1, ORC4, ORC6, CDT1, CDC6, CDC45L, MCM5 and GMNN). Most forms of MGS are inherited in an autosomal recessive inheritance pattern. MGS type 6 (GMNN gene) is inherited in an autosomal dominant pattern.
Recessive genetic conditions occur when an individual inherits a non-working gene from each parent. If an individual receives one working gene and one non-working gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the non-working gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier, like the parents, is 50% with each pregnancy. The chance for a child to receive working genes from both parents is 25%. The risk is the same for males and females.
Recessive conditions are more common in people born to parents who are biologically related (consanguineous).
Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a new gene change in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
Since MGS was first described in 1959, only about 67 cases have been reported in the medical literature (Nov 2019). MGS is estimated to affect less than 1-9 individuals per 1,000,000 people. However, researchers believe this condition is under-diagnosed. MGS affects men and women equally.
MGS is diagnosed based on the clinical signs and symptoms. The presence of small ears, very small or absent kneecaps and short stature are essential for the clinical diagnosis of MGS.
MGS may be diagnosed at birth, based on detailed medical history, physical examination, and other tests, including imaging of the kneecaps. Further bone development may be diagnosed through careful view of the entire bone system using imaging options such as an x-ray.
Genetic testing for changes in the ORC1, MCM5, GMNN, CDC45, ORC4, ORC6, CDT1, or CDC6 genes can confirm a suspected diagnosis. Gene changes have been detected in about 78% of patients with MGS.
Clinical Testing and Work-Up
In infants with suspected MGS, ultrasound is advised to view the kneecaps. Kneecaps are not able to be seen on x-rays within the first 5-6 years of life.
There are no official guidelines for diagnostic evaluation for MGS patients. However, it is recommended to have a hearing evaluation, a cardiac evaluation, knee imaging, and a developmental growth evaluation, with other evaluations as needed based on symptoms.
Treatment
The treatment of MGS is directed towards specific symptoms or complaints. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, surgeons, specialists who assess and treat hearing problems (audiologists), those who specialize in diagnosing and treating skeletal defects (orthopedists), and other health care professionals may be involved.
Pediatricians need to closely monitor an affected child’s feeding, growth patterns, and breathing problems. This is important since poor weight gain and recurrent infections are the most serious problems associated with MGS during early infancy and childhood.
Genetic counseling is recommended for affected individuals, their siblings and parents.
Information on current clinical trials is at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (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:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., ear abnormalities, short stature, skeletal malformations, etc.].)
JOURNAL ARTICLES
Belaid R, Zouaoui H, Yazidi M, et al. Meier-Gorlin syndrome: an additional case report in an adult woman. Clinical Dysmorphology. 2019;28(2):86-90.
Morankar RG, Goyal A, Gauba K, Kapur A. Dentofacial characteristics in a child with Meier–Gorlin syndrome: A rare case report. Saudi Dent J. 2018;30(3):260-264.
de Munnik SA, Hoefsloot EH, Roukema J, et al. Meier-Gorlin syndrome. Orphanet Journal of Rare Diseases. 2015;10(1):114.
Munnik SA de, Otten BJ, Schoots J, et al. Meier–Gorlin syndrome: Growth and secondary sexual development of a microcephalic primordial dwarfism disorder. American Journal of Medical Genetics Part A. 2012;158A(11):2733-2742.
Faqeih E, Sakati N, Teebi AS. Meier-Gorlin (ear-patella-short stature) syndrome: growth hormone deficiency and previously unrecognized findings. Am J Med Genet A. 2005;137:339-41.
Shalev SA, Hall JG. Another adult with Meier-Gorlin syndrome–insights into the natural history. Clin Dysmorphol. 2003;12:167-9.
Cohen A, Mulas R, Seri M, et al. Meier-Gorlin syndrome (ear, patella, short stature syndrome) in an Italian patient: Clinical evaluation and analysis of possible candidate genes. Am J Med Genet. 2002;107:48-51.
Bongers EM, Opitz JM, Fryer A, et al. Meier-Gorlin syndrome: report of eight additional cases and review. Am J Med Genet. 2001;102:115-24.
Loeys BL, Lemmerling MM, Van Mol CE, et al. The Meier-Gorlin syndrome, or ear-patella-short stature syndrome, in sibs. Am J Med Genet. 1999;84:61-67.
Teebi AS, Gorlin RJ. Not a new Seckel-like syndrome but ear-patella-short stature syndrome. Am J Med Genet. 1997;70:454.
Boles RG, Teebi AS, Schwartz D, et al. Further delineation of the ear, patella, short stature syndrome (Meier-Gorlin syndrome). Clin Dysmorphol. 1994;3:207-14.
Cohen B, Temple IK, Symons JC, et al. Microtia and short stature: a new syndrome. J Med Genet. 1991;28:786-790.
Hurst JA, Winter RM, Baraitser M. Distinctive syndrome of short stature, craniosynostosis, skeletal changes, and malformed ears. Am J Med Genet. 1988;29:107-15.
INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:224690; Last Update: 7/10/17. Available at: https://www.omim.org/entry/224690 Accessed July 27, 2020.
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Aprende más 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.
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