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. Spinal abnormalities have been reported. 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 several 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, most notably in exon 22 but at other locations as well. 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 70 cases have been reported.
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:
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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
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