You are here: Home / Rare Disease Information / Rare Disease Database

Search Rare Diseases

Enter a disease name or synonym to search NORD's database of reports.

0-9 - A - B - C - D - E - F - G - H - I - J - K - L - M - N - O - P - Q - R - S - T - U - V - W - X - Y - Z

Mulvihill Smith Syndrome

Synonyms of Mulvihill Smith Syndrome

  • progeriod short stature with pigmented nevi

Disorder Subdivisions

  • No subdivisions found.

General Discussion

Mulvihill-Smith syndrome is an extremely rare disorder characterized by low birth weight; growth delays leading to short stature (dwarfism); and/or a prematurely aged facial appearance. Other findings may include additional abnormalities of the head and facial (craniofacial) areas, multiple deeply-colored skin lesions (pigmented nevi), hearing impairment, and/or mental retardation. Eventually, some affected individuals may develop diminished capabilities to resist and fight off repeated infections (primary immunodeficiency). The range and severity of symptoms varies from case to case. All reported cases of Mulvihill-Smith syndrome have occurred as isolated cases. It is possible that this condition is due to a new dominant gene mutation.


Mulvihill-Smith syndrome is an extremely rare disorder characterized by low birth weight; an abnormally small head (microcephaly) and/or body; and progressive growth delays resulting in short stature (dwarfism). Affected individuals may also exhibit characteristic facial malformations, additional physical abnormalities, and/or mild to moderate mental retardation. The range and severity of symptoms vary from case to case.

Individuals with Mulvihill-Smith syndrome exhibit characteristic abnormalities of the head and facial (craniofacial) area. Many individuals may lack the layer of fatty tissue directly beneath the skin of the face (facial subcutaneous fat), resulting in a prematurely aged or "bird-like" facial appearance. In addition, affected individuals may have an abnormally small face; severely underdeveloped jaws (marked micrognathia); a small, pointed chin; and/or absence of several teeth (oligodontia). Infants and children with Mulvihill-Smith syndrome also typically exhibit deeply-colored skin lesions like freckles or warts (pigmented nevi) on the skin of the face, neck, hands, trunk, and/or other parts of the body.

Some individuals with Mulvihill-Smith syndrome may also exhibit a variety of additional abnormalities. Affected individuals may experience hearing loss (sensorineural), particularly involving sounds that are highly-pitched. They may also have difficulty learning to speak and/or may have unusually high-pitched voices. Although some individuals with the disorder may have normal intelligence others, may exhibit mild, moderate, or severe mental retardation.

In addition, some affected individuals may exhibit other unusual physical characteristics. For example, affected children may demonstrate abnormal sideways curvature of the spine involving the chest (thoracic scoliosis) and/or impaired joint mobility. Some affected males may exhibit genital abnormalities, such as abnormal placement of the urinary opening (meatus) on the underside of the penis (hypospadias), causing the penis to point downward (chordee). In addition, some affected individuals may experience episodes of recurrent vomiting (cyclic vomiting). This repeated vomiting may result in damage to the tube that carries food from the mouth to the stomach (esophageal ulceration).

In some cases, individuals with Mulvihill-Smith syndrome may also develop an increased susceptibility to repeated respiratory and other infections (primary immunodeficiency). In addition, abnormal protrusion of the front (anterior), clear portion of the eye through which light passes (cornea) (keratoconus) has been identified, in at least one case, as an incidental finding.


All reported cases of Mulvihill-Smith syndrome have occurred as isolated cases. It is possible that this condition is due to a new dominant gene mutation.

Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary for the appearance of the disease. The abnormal gene can be inherited from either parent, or can be the result of a new mutation (gene change) in the affected individual. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy regardless of the sex of the resulting child.

Affected Populations

Mulvihill-Smith syndrome is an extremely rare disorder that, in theory, affects males and females in equal numbers. Most of the reported cases, however, have been males. Only seven cases have been reported.

Related Disorders

Symptoms of the following disorders may be similar to those of Mulvihill-Smith syndrome. Comparisons may be useful for a differential diagnosis:

Cerebro-oculo-facio-skeletal syndrome (COFS) is a pediatric, genetic disorder that involves the brain and the spinal cord. It is characterized by craniofacial and skeletal abnormalities, severely reduced muscle tone, and impairment of reflexes. Symptoms may include large, low-set ears, small eyes, microcephaly (abnormal smallness of the head), micrognathia (abnormal smallness of the jaws), clenched fists, wide-set nipples, vision impairments, involuntary eye movements, and mental retardation, which can be moderate or severe. Respiratory infections are frequent. COFS is diagnosed at birth. Ultrasound technology can detect fetuses with COFS at an early stage of pregnancy, as the fetus moves very little, and some of the abnormalities result, in part, from lack of movement.

Cockayne syndrome (CS) and Mulvihill-Smith syndrome share several features or symptoms. For example, persons affected by either syndrome will present with short stature (dwarfism), "bird-like face" with pointed chin and nose (precociously senile appearance), and mental retardation, and a number of other of multisystemic disease. Cockayne syndrome is an autosomal recessive genetic disorder. CS is a disorder caused by a malfunction of the cell's normal process of repairing damaged DNA (DNA excision and repair).

LEOPARD syndrome is an extremely rare inherited disorder. The term "LEOPARD" is an acronym meaning (L)entigenes (small dark spots on the skin); (E) electrocardiogram abnormalities; (O)cular hypertelorism (widely spaced eyes); (P)ulmonary stenosis (abnormal narrowing of the opening between the pulmonary artery and the right ventricle of the heart); (A)nomalies of the genitals; (R)etarded growth; and (D)eafness. Lentigenes may be apparent at (congenital) or shortly after birth. Genital anomalies may include failure of the testes to descend into the scrotum (cryptorchidism) and abnormal placement of the urinary opening on the underside of the penis (hypospadias). Most affected individuals also exhibit growth retardation. In addition, in some cases, mild mental retardation may be present. LEOPARD Syndrome is thought to be inherited as an autosomal dominant genetic trait. (For more information on this disorder, choose "LEOPARD" as your search term in the Rare Disease Database.)

Nucleotide excision repair disorders result from a breakdown of the process that repairs damaged DNA in the cell. A person's genetic material is protected by several repair systems. Environmental factors, e.g. ultraviolet light and exposure to radiation, as well spontaneous mutations can cause damage (lesions) to the strands of DNA. Nucleotide excision repair is one of the more important and useful DNA repair systems. DNA repair disorders occur when this process does not work properly. Examples of DNA repair disorders include xeroderma pigmentosum (XP) and Cockayne's syndrome (CS), and PIBIDS, a recently recognized disorder involving a photosensitive form of the brittle hair disorder, trichothiodystrophy.

Progeria is a rare condition in which affected individuals have a premature aged appearance. Characteristic features include gray hair or baldness; wrinkled skin; loss of fat, resulting in thin limbs and sagging skin; short stature; and/or internal abnormalities such as thickening of artery walls, resulting in impaired blood flow (atherosclerosis). The two main forms of progeria are Hutchinson-Gilford progeria syndrome, which affects children, and Werner syndrome, which affects adults. (For more information on these disorders, choose "Hutchinson Gilford progeria" and 'Werner" as your search terms in the Rare Disease Database.)

Standard Therapies

The diagnosis of Mulvihill-Smith Syndrome may be suspected upon the identification of characteristic physical features and findings (e.g., low birth weight, lack of subcutaneous fat in the face, etc.). A diagnosis may be confirmed based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests. For example, hearing tests may be performed to determine the range and severity of hearing impairment in each individual. Pigmented nevi may be present at birth (congenital) or shortly after birth. Other characteristic findings (e.g., short stature) may not be apparent until a child is older.

The treatment of Mulvihill-Smith Syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians; physicians who diagnose and treat abnormalities of the skin (dermatologists); speech pathologists; specialists who assess and treat hearing problems (audiologists); specialists who diagnose and treat skeletal abnormalities; and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.

Specific therapies for the treatment of Mulvihill-Smith Syndrome are symptomatic and supportive. Genetic counseling may be of benefit for affected individuals and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at 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

For information about clinical trials sponsored by private sources, contact:

Mulvihill Smith Syndrome Resources

(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., hearing impairment, short stature, etc.]).



Gorlin RJ, Cohen MMJr, Levin LS. Eds. Syndromes of the Head and Neck. 3rd ed. Oxford University Press, London, UK; 1990:487-88.

Winter RM, Baraitser M. Multiple Congenital Anomalies. Chapman & Hall Medical. London, UK. 1991:424.

Lehmann A. Ageing: repair and transcription keep us from premature ageing. Curr Biol. 2002;12:R550-51.

Martin GM, Oshima J. Lessons from human progeroid syndromes. Nature. 2000;408:263-66.

Bartsch O, Ludwig D, Schwinger E, et al. Severe complications and gastric carcinoma in Mulvihill- Smith syndrome. J Med Genet. 1999;36:175.

De Silva, Wheatley DN, Herriot R, et al. Mulvihill-Smith progeria-like syndrome: a further report with delineation of phenotype, immunologic deficits, and novel observation of fibroblast abnormalities. Am J Med Genet. 1997;69:56-64.

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Progeroid Short Stature with Pigmented Nevi. Entry Number; 176690: Last Edit Date; 5/11/1999.

Mulvihill-Smith syndrome. Multiple Congenital Analogy/Mental Retardation (MCA/MR) Syndromes. nd. 2pp.

SignList. Progeria short stature pigmented nevi. orphanet. nd. 1p.

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Report last updated: 2008/04/25 00:00:00 GMT+0

0-9 - A - B - C - D - E - F - G - H - I - J - K - L - M - N - O - P - Q - R - S - T - U - V - W - X - Y - Z

NORD's Rare Disease Information Database is copyrighted and may not be published without the written consent of NORD.

Copyright ©2015 NORD - National Organization for Rare Disorders, Inc. All rights reserved.
The following trademarks/registered service marks are owned by NORD: NORD, National Organization for Rare Disorders, the NORD logo, RareConnect. .