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 diagnosed based on a series of symptoms described in the scientific literature. There can be some variation of symptoms between affected individuals. The core symptoms include the following:

Abnormally Small head (microcephaly) – Microcephaly is a rare condition in which a child’s head size is significantly smaller compared to children of the same age and sex. Microcephaly is usually caused by abnormal brain development in the womb or failure of the brain to grow after birth. This characteristic has been reported in a 100% of individuals diagnosed with Mulvihill-Smith syndrome.

Intellectual disabilities – Children with Microcephaly tend to have Intellectual disabilities that range from mild to severe. 82% of individuals diagnosed with Mulvihill-Smith syndrome had some type of intellectual disabilities. In most patients, Intellectual disabilities result from slower brain development during childhood, but in a few patients, some cognitive deterioration in adulthood has also been reported.

Psychological symptoms – Individuals diagnosed with Mulvihill-Smith syndrome have been reported to have various psychological symptoms such as major mood swings, periods of agitation, aggression, Depression and insomnia. Sleep disorders have also been reported.

Abnormal facial features – Individuals with Mulvihill-Smith syndrome can have various abnormal facial features. The majority of diagnosed patients (10/11) showed reduced levels of the layer of fatty tissue directly beneath the skin of the face (facial subcutaneous fat). In 4 patients, abnormally large distance between the eyes (hypertelorism) was reported. In addition, affected individuals may have an abnormally small face, a severely underdeveloped jaw (micrognathia), a small, pointed chin; and/or absence of one or more teeth (hypodontia). Taken together, these changes in facial features lead to a narrower face and several scientific papers described patients as having a “bird-like” facial appearance. The abnormal structures in the face may be the reason these patients often have a high pitched voice (reported in 9 cases).

Sensory issues – Deafness has been reported in 91% of individuals diagnosed with Mulvihill-Smith syndrome. Clouding of lens in the eye that can impair vision (cataracts) have been reported in three individuals with Mulvihill-Smith syndrome.

Shortness in height and other anatomic abnormalities – Short stature is a central characteristic of Mulvihill-Smith syndrome, as it has been reported in 91% of individuals. In addition, some afflicted individuals may have physical characteristics such as abnormally bent or curved fingers (clinodactyly) and shortened fingers and toes (brachydactyly). Some affected children may have an abnormal sideways curvature of the spine involving the chest (thoracic scoliosis) and/or impaired joint mobility. Some affected males may have 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). Low birth weight has been reported as a common trait in patients diagnosed with Mulvihill-Smith syndrome.

Impaired immune system (immunodeficiency) – The ability of the body’s immune system to fight invading organisms seems to be impaired in individuals with Mulvihill-Smith syndrome. In several patients, analysis of blood revealed reduced levels of key cells of the immune system (T- and B-cells). In addition, reoccurring infection occured in 91% of individuals diagnosed with Mulvihill-Smith syndrome. Impaired immune function is often associated with increased risk of cancer, and 4 patients had various tumors (gastric, tongue, pancreas, and melanoma). These cancers occurred in individuals aged 16-28 years old. An impaired immune system is seen as a hallmark characteristic of Mulvihill-Smith syndrome, and often used to distinguish it from other premature aging diseases such as Cockayne syndrome.

Multiple non-cancerous Moles (pigmented nevi) – 100% of patients with Mulvihill-Smith syndrome have been reported to have excessive Moles on the face. These pigmented nevi may be present at birth (congenital) or shortly after birth. A high number of Moles is a symptom seen in several other diseases associated with a compromised immune system. Some infants and children with Mulvihill-Smith syndrome also have numerous freckles or dark pigmented Lesions (pigmented spitz nevus) on the skin of the face, neck, hands, trunk and/or other parts of the body.

Premature aging (progeroid syndrome) – Individuals with Mulvihill-Smith syndrome have been described as looking older in their physical appearance, particularly the face. This advanced aging appearance along with the fact that affected individuals develop conditions more often seen in older populations such as cataracts, cancer and vulnerability to infections has led to this condition being described as a progeroid syndrome. Some patients with Mulvihill-Smith syndrome have been reported to have elevated levels of cholesterol (hypercholesterolemia), another condition usually observed in older populations. Mulvihill-Smith syndrome is one of about 30 diseases associated with premature aging.

The cause of Mulvihill-Smith syndrome is not presently known. All reported affected individuals have been isolated and independent cases. This makes it likely that the disease results from a new spontaneous mutation in a gene or gene(s) or caused by other genetic defects (chromosome abnormalities). The possibility that the disease may be inherited (autosomal recessive inheritance) has been suggested in one scientific paper. Autosomal recessive diseases occur when the affected individual inherits two abnormal copies of the gene, one from each parent. It is also possible that the disease is both autosomal recessive and spontaneous, with one mutation inherited from one parent and the other mutation arising spontaneously. No specific genes associated with Mulvihill-Smith syndrome have been identified, so this condition cannot be identified through genetic testing. Mulvihill-Smith syndrome is diagnosed by the symptoms that have been described above.

Because the cause of the disease is unknown, there is no direct or specific treatment available for Mulvihill-Smith syndrome. Because of the complex nature of the disease, 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 manage an afflicted person’s symptoms. Overall, therapies for the treatment of Mulvihill-Smith syndrome are symptomatic and supportive.

Mulvihill-Smith syndrome is an extremely rare disorder (11 reported cases) that, in theory, affects males and females in equal numbers. Most of the reported affected individuals, however, have been males (7 males, 4 females).

There is no cure for Mulvihill smith syndrome. Therapies are focused on managing the specific symptoms that are apparent in each individual.