NORD gratefully acknowledges 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 and cranio-facial abnormalities with 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, as well as spine deformities. 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. 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:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
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
Jones KL. Ed. Smith’s Recognizable Patterns of Human Malformation. 5th ed. Philadelphia, PA: W. B. Saunders Co.; 1997:588-89.
Gorlin RJ, Cohen MMJr, Levin LS. Eds. Syndromes of the Head and Neck. 3rd ed. London, UK: Oxford University Press; 1990:277-80.
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.
Verloes A, Lesenfants S, Barr M, et al. Fronto-otopalatodigital osteodysplasia: clinical evidence for a single entity encompassing Melnick-Needles syndrome, otopalataodigital syndrome types 1 and 2, and frontometaphyseal dysplasia. Am J Med Genet. 2000;90:407-22.
Albano LM, Kim CA, Lee VK, et al. Clinical and radiological aspects in Melnick-Needles syndrome. Rev Hosp Clin Fac Med Sao Paulo. 1999;54:69-72.
Nishimura G, Horiuchi T, Kim OH, et al. Atypical skeletal changes in otopalatodigital syndrome type II: phenotypic overlap among otopalatodigital syndrome type II, boomerang dysplasia, atelosteogenesis Type I and type III, and lethal male phenotype of Melnick-Needles syndrome. Am J Med Genet. 1997;73:132-38.
Robertson S, Gunn T, Allen B, et al. Are Melnick-Needles syndrome and oto-palato-digital syndrome type II allelic? Observations in a four-generation kindred. Am J Med Genet. 1997;71:341-47.
Neou P, Kyrkanides S, Goureli E, et al. Melnick-Needles syndrome in a mother and her son. Genet Cous. 1996;7;123-29.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Melnick-Needles Syndrome; MNS. Entry No: 309350. Last Edited 3/04/2015. Available at: http://omim.org/entry/309350 Accessed May 11, 2015.
Melnick-Needles osteodysplasty. Orphanet. http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2484 Last Update September 2014. Accessed May 11, 2015.
The information in NORD’s Rare Disease Database is for educational purposes only and is not intended to replace the advice of a physician or other qualified medical professional.
The content of the website and databases of the National Organization for Rare Disorders (NORD) is copyrighted and may not be reproduced, copied, downloaded or disseminated, in any way, for any commercial or public purpose, without prior written authorization and approval from NORD. Individuals may print one hard copy of an individual disease for personal use, provided that content is unmodified and includes NORD’s copyright.
National Organization for Rare Disorders (NORD)
55 Kenosia Ave., Danbury CT 06810 • (203)744-0100