National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Mulibrey Nanism is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
Related Disorders List
Information on the following diseases can be found in the Related Disorders section of this report:
- Russell-Silver Syndrome
- Robinow Syndrome
- Primary Empty Sella Syndrome
Mulibrey nanism is an extremely rare autosomal recessive genetic disorder characterized by profound growth delays and distinctive abnormalities of the muscles, liver, brain, and eyes. The acronym MULIBREY stands for (MU)scle, (LI)ver, (BR)ain, and (EY)e. Nanism is another word for dwarfism. A characteristic feature not included in the original acronym is the overgrowth of the fibrous sac that surrounds the heart restricting normal filling of the heart (constrictive pericarditis). Characteristic symptoms may include low birth weight, short stature, and severe progressive growth delays. Muscles are usually underdeveloped and lack normal tone (hypotonia). Some infants with this disorder may have an abnormally large liver (hepatomegaly). Infants typically have yellow discoloration in their eyes.
Mulibrey nanism is characterized by progressive growth failure that begins prenatally. Muscle hypotonia is frequently seen and newborns often have characteristic abnormalities of the head and face including a triangularly shaped face. Yellow discoloration deep within the eyes (ocular fundi) and other ocular abnormalities may be present but vision is usually normal. The voice is characteristically high-pitched. More than 90 percent of affected individuals have a J-shaped sella turcica, which is a depression in the sphenoid bone at the base of the skull.
Infants with mulibrey nanism may also exhibit symptoms related to overgrowth of the fibrous sac surrounding the heart (constrictive pericarditis). When constrictive pericarditis is present at birth, affected infants may have a bluish discoloration of the skin (cyanosis), especially on the lips and fingertips.
Other symptoms may include abnormally prominent veins in the neck, congestion in the lungs, abnormal fluid accumulation in the abdomen (ascites), swelling of the arms and/or legs (peripheral edema), and/or enlargement of the heart (cardiac hypertrophy) and/or liver (hepatomegaly). There may also be elevated pressure in the veins, congestion or blockage in the main artery serving the lungs (pulmonary artery), and/or a build-up of fibrous tissue in the walls of the lungs (pulmonary fibrosis). Associated complications of these conditions may lead to congestive heart failure.
In some cases, individuals with mulibrey nanism may have additional physical abnormalities, such as an unusually thin shinbone (fibrous tibia dysplasia). Large cerebral ventricles in the brain and delayed motor development are uncommon findings. Most affected individuals have normal intelligence.
Individuals with mulibrey nanism often have underdevelopment of various endocrine glands that leads to hormone deficiencies. Delayed puberty sometimes occurs accompanied by infrequent or very light menstrual periods. Females have an increased risk for premature ovarian failure and ovarian tumors.
Mulibrey nanism is caused by an abnormality in the TRIM37 gene located on chromosome 17 at 17q22-q23 and is inherited as an autosomal recessive genetic disorder.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 17q22-23" refers to bands 22-23 on the short arm of chromosome 17. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one 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 defective gene and, therefore, have an affected child is 25 percent with each pregnancy. The risk to have a child who is a carrier like the parents is 50 percent with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25 percent. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Mulibrey nanism is an extremely rare disorder that affects males and females in equal numbers. Approximately 110 patients have been reported worldwide with this condition. Most of the reported cases are from Finland but this condition has also occurred in North America, South America, Central America, Spain, France and Egypt.
Symptoms of the following disorders can be similar to those of mulibrey nanism. Comparisons may be useful for a differential diagnosis:
Russell-Silver syndrome is a rare growth disorder and affected individuals are frequently very short (dwarfism). Intelligence is often normal, however, in some cases, mental retardation may occur. Some developmental abnormalities may improve with age. Infants with this disorder are usually small at birth. Physical abnormalities of the face and head (craniofacial area) may include a small triangular face, downwardly turned corners of the mouth, and a prominent forehead. The head, although normal in size, may appear large in comparison to the body. In some cases, organs may be larger on one side of the body than the other (asymmetry). Other symptoms of this disorder may include unusually short arms; short, inwardly curved fifth fingers; brown spots on the skin (cafe-au-lait spots); webbed toes (syndactyly); and/or failure of the testes to descend into the scrotum (cryptorchidism) in affected males. The exact cause of this syndrome is unknown. (For more information on this disorder, choose "Russell-Silver" as your search term in the Rare Disease Database.)
Robinow syndrome is an extremely rare inherited disorder characterized by mild to moderate short stature due to growth delays after birth (postnatal growth retardation); distinctive abnormalities of the head and facial (craniofacial) area; additional skeletal malformations; and/or genital abnormalities. Characteristic craniofacial features may include an abnormally large head (macrocephaly) with a bulging forehead (frontal bossing); widely spaced eyes (ocular hypertelorism) that are abnormally prominent; a small, upturned nose with nostrils that are flared forward (anteverted); and/or a sunken (depressed) nasal bridge. Skeletal malformations may include forearm bones (radius and ulna) that are unusually short (forearm brachymelia), abnormally short fingers and toes, permanent fixation of the fifth fingers in a bent position (clinodactyly), unusually small hands with broad thumbs, malformation of the ribs, abnormal side-to-side curvature of the spine (scoliosis), and/or underdevelopment of one side of the bones in the middle (thoracic) portion of the spinal column (hemivertebrae). Genital abnormalities associated with Robinow syndrome may include an abnormally small penis (micropenis) and failure of the testes to descend into the scrotum (cryptorchidism) in affected males and underdevelopment (hypoplasia) of the clitoris and the outer, elongated folds of skin on either side of the vaginal opening (labia majora) in affected females. The range and severity of symptoms vary from case to case. (For more information on this disorder, choose "Robinow" as your search term in the Rare Disease Database.)
The primary form of empty sella syndrome is a rare inherited disorder of the brain that is transmitted as an autosomal dominant trait. The disorder is characterized by an empty space filled with cerebrospinal fluid in the sella turcica area of the brain. The area fills with fluid as a result of a defect in the sella diaphragm. Symptoms and findings may include unusual facial features, a high arched palate, moderate short stature, increased bone density (osteosclerosis), and normal pituitary function. (For more information on this disorder, choose "empty sella" as your search term in the Rare Disease Database.).
Mulibrey nanism may be diagnosed at birth by a thorough clinical evaluation, characteristic physical findings, and specialized tests. Such tests may include x-ray studies, which may show abnormal calcium deposits in the sac surrounding the heart (pericardium); studies measuring the electrical activity of the heart (electrocardiograms or EKGs); and/or examination with a device that visualizes the interior of the eye which may detect ocular abnormalities. Molecular genetic testing for the TRIM37 gene is available to confirm the diagnosis.
Constrictive pericarditis may be treated with surgery. Diuretics and digoxin may be prescribed for progressive heart failure. Hormone replacement therapy should be offered to children with growth hormone deficiency, delayed puberty, infrequent or very light menstrual periods, hypothyroidism, hypoadrenocorticism and abnormal ovaries or testes. Females with mulibrey nanism should be monitored closely for ovarian tumors.
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 website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Grimberg A. Mulibrey Nanism. In: The NORD Guide to Rare Disorders, Philadelphia: Lippincott, Williams and Wilkins, 2003:224.
Avela K, Lipsanen-Nyman M, Idanheimo N, et al. Gene encoding a new RING-B-box-coil protein is mutated in mulibrey nanism. Nat Genet 2000;25:298-301.
Jagiello P, Hammans C, Wieczorek S, et al. A novel splice site mutation in the TRIM37 gne causes mulibrey nanism in a Turkish amily with phenotypic heterogeneity. Hum Mutat 2003;21:630-635.
Karlberg N Jalanko H, Perheentupa J, et al. Mulbrey nanism:clinical features and diagnostic criteria. J Med Genet 2004;41:92-98.
Karlberg S, Tiitinen A and Lipsanen-Nyman M. Failure of sexual maturation in mulibrey nanism (letter) New Engl J Med 2004;351:2559-2560.
FROM THE INTERNET
McKusick VA, ed. Online Mendelian Inheritance in Man (OMIM). Baltimore, MD: The Johns Hopkins University:Entry No. 253250; Last Update:1/11/05.
Human Growth Foundation
997 Glen Cove Avenue
Glen Head, NY 11545
4340 East West Highway Ste 950
Bethesda, MD 20814
Little People of America, Inc.
250 El Camino Real Suite 201
Tustin, CA 92780
American Heart Association
7272 Greenville Avenue
Dallas, TX 75231
NIH/National Eye Institute
31 Center Dr
Bethesda, MD 20892-2510
Coalition for Heritable Disorders of Connective Tissue (CHDCT)
4301 Connecticut Avenue, NW Suite 404
Washington, DC 20008
Hydrocephalus Support Group, Inc.
1933 Mistflower Glen Ct.
Chesterfield, MO 63005-4236
Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126
For a Complete Report
This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.
The information provided in this report is not intended for diagnostic purposes. It is provided for informational purposes only. NORD recommends that affected individuals seek the advice or counsel of their own personal physicians.
It is possible that the title of this topic is not the name you selected. Please check the Synonyms listing to find the alternate name(s) and Disorder Subdivision(s) covered by this report
This disease entry is based upon medical information available through the date at the end of the topic. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder.
For additional information and assistance about rare disorders, please contact the National Organization for Rare Disorders at P.O. Box 1968, Danbury, CT 06813-1968; phone (203) 744-0100; web site www.rarediseases.org or email email@example.com
Last Updated: 4/12/2008
Copyright 1996, 1998, 2006 National Organization for Rare Disorders, Inc.
Healthwise, Healthwise for every health decision, and the Healthwise logo are trademarks of Healthwise, Incorporated.