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NORD is very grateful to Jeffrey A. Wong, MD, FACC, Division of Pediatrics, Cedars-Sinai Medical Center and The Heart Center, Children's Hospital of Los Angeles, for assistance in the preparation of this report.
Melnick-Needles syndrome (MNS) is a genetic disorder of bone characterized by skeletal abnormalities and a specific facial appearance. The skeletal abnormalities include bowing of long bones, s-curved leg bones, ribbon-like ribs and a hardening of the skull base. The typical facial features include prominent, protruding eyes, full cheeks, an extremely small lower jaw and a hairy forehead. The condition may affect many bones of the body causing deformity and in some cases short stature. MNS is thought to be inherited as an X-linked dominant genetic disorder.
Individuals with MNS have a particular facial appearance with prominent, widely-spaced eyes, full cheeks, small facial bones, and an unusually small lower jaw (micrognathia). The skull may be slow to develop and the way in which affected individuals bring their teeth together (bite) may be abnormal.
The upper arms and the last bones in the fingers (distal phalanges) may be shorter than normal. One of the short bones of the arm (radius) and of the leg (fibula) may be bowed. The distal (farthest from the body) ends of the long bone of the arm (humerus) and of the two short bones of the leg (tibia, fibula) may be flared. The connection between the long bone of the leg (femur) and the hip may be misaligned (coxa valga), producing an unusual walking pattern (gait).
Those affected with MNS may also have a relatively small chest cavity (thoracic cage) with irregular ribbon-like ribs, a short collarbone (clavicle), and narrow shoulders. The lower part of their chest has a hollow shape (pectus excavatum). The vertebrae may be longer than normal. Part of the pelvis (ilium) may also be flared.
Occasionally, dislocation of the hip may occur. Other abnormalities may also be noted. The tube that runs from the kidney to the bladder (ureter) may be abnormally narrow. This may lead to urine retention and kidney problems. Congenital heart defects (heart problems that a baby is born with) and high blood pressure in the lungs have also been reported in those with MNS.
Individuals with MNS may develop osteoarthritis of the back and/or hip in later years. The shape of the pelvis in females may make normal childbirth difficult. Those affected may be unusually susceptible to respiratory infections. Height usually is not affected, but growth hormone deficiency was found in two patients.
Intellectual development is normal in individuals with this condition.
MNS is more severe and lethal in males. Abnormalities seen in affected males include bulging eyes, protrusion of internal organs through the abdominal wall (omphalocele) and major skeletal abnormalities.
MNS is an X-linked dominant disorder caused by an abnormality (mutation) in the FLNA gene which codes for the cytoskeletal protein filamin A. The abnormal gene has been mapped to chromosome Xq28.
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 Xq28" refers to band 28 on the long arm of the X chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
X-linked dominant disorders are caused by an abnormal gene on the X chromosome and occur mostly in females. Females with these rare conditions are affected when they have an X chromosome with the gene for a particular disease. Males with an abnormal gene for an X-linked dominant disorder are more severely affected than females and often do not survive.
MNS usually occurs as the result of a new mutation without any apparent family history, though familial inheritance has been noted.
MNS occurs in females much more often than in males. Approximately 50 cases have been reported.
Symptoms of the following disorder can be similar to those of Melnick-Needles syndrome. Comparisons may be useful for a differential diagnosis:
Multiple epiphyseal dysplasia is a hereditary bone disorder that affects females and males equally. It is detectable between two and five years of age with the appearance of a waddling gait. Patients may experience pain as a result of osteoarthritis in the joints. Body size tends to be almost normal, with the exception of the hands and feet which are disproportionately small. (For more information on this condition, choose "multiple epiphyseal dysplasia" as your search term in the Rare Disease Database.)
Treatment of MNS is symptomatic and supportive. Genetic counseling may be of benefit for patients and their families.
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:
Tollfree: (800) 411-1222
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For information about clinical trials sponsored by private sources, contact:
Contact for additional information about Melnick-Needles syndrome:
Jeffrey A. Wong, MD, FACC
Division of Pediatrics, Cedars-Sinai Medical Center
The Heart Center, Children’s Hospital of Los Angeles
PO Box 8126
Gaithersburg, MD 20898-8126
Phone #: 301-251-4925
800 #: 888-205-2311
Home page: http://rarediseases.info.nih.gov/GARD/
4, Kivner Lane
East Sussex, TN40 2ST United Kingdom
Phone #: 014-242-17790
800 #: --
Home page: http://www.melnickneedlesyndrome.com
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Akin L, Adal E, Akin MA, et al. Melnick-Neeldes syndrome associated with growth hormone deficiency: A case report. J Clin Res Ped Endo. 2009;1(5):248-51.
Robertson SP, Twigg SR, Sutherland-Smith AJ, et al. Localized mutations in the gene encoding the cytoskeletal protein filamin A cause diverse malformations in humans. Nat Genet. 2003;33:487-91.
Kristiansen M, Knudsen GP, Soyland A, et al. Phenotypic variation in Melnick-Needles syndrome is not reflected in X inactivation patterns from blood or buccal smear. Am J Med Genet. 2002;108:120-27.
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Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Melnick-Needles Syndrome; MNS. Entry No: 309350. Last Edited July 28, 2009. Available at: http://www.ncbi.nlm.nih.gov/omim/. Accessed July 13, 2012.
Melnick-Needles osteodysplasty. Orphanet. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2484 Last Update February 2005. Accessed July 13, 2012.
Report last updated: 2012/07/17 00:00:00 GMT+0