10 Unusual Genetic Mutations in HumansS

No two people are alike, due to the subtly different ways our genomes are expressed. But sometimes these biological differences lead to genetic mutations that are extremely rare, and sometimes debilitating. Historically, many people suffering from these mutations were labeled monsters or freaks — but today, we know they are simply part of the broad spectrum of genetic variations in our species. Here are 10 of the most unusual genetic mutations we've identified in humans.

1. Progeria

This genetic disorder is as rare as it is severe. The classic form of the disease, called Hutchinson-Gilford Progeria, causes accelerated aging.

10 Unusual Genetic Mutations in Humans

Most children who have progeria essentially die of age-related diseases around the age of 13, but some can live into their 20s. Death is typically caused by a heart attack or stroke. It affects as few as one per eight million live births.

The disease is caused by a mutation in the LMNA gene, a protein that provides support to the cell nucleus. Other symptoms of progeria include rigid (sclerotic) skin, full body baldness (alopecia), bone abnormalities, growth impairment, and a characteristic “sculptured” nasal tip.

Progeria is of great interest to gerontologists who hope connect genetic factors to the aging process. Image: HBO.

2. Uner Tan Syndrome

10 Unusual Genetic Mutations in Humans

Uner Tan syndrome is a somewhat controversial condition, whose most obvious property is that people who suffer from it walk on all fours. UTS is a syndrome that was proposed by the Turkish evolutionary biologist Üner Tan after studying five members of the Ulaş family in rural Turkey. These individuals walk with a quadrupedal locomotion, use primitive speech, and have a congenital brain impairment (including “disturbed conscious experience”). The family was featured in a 2006 BBC2 documentary called, "The Family That Walks On All Fours." Tan describes it like this:

The genetic nature of this syndrome suggests a backward stage in human evolution, which is most probably caused by a genetic mutation, rendering, in turn, the transition from quadrupedality to bipedality. This would then be consistent with theories of punctuated evolution.

The new syndrome, says Tan, “may be used as a live model for human evolution.” Some experts think this is bunk, and that genetics may have very little to do with it.

10 Unusual Genetic Mutations in HumansS

3. Hypertrichosis

Hypertrichosis is also called “werewolf syndrome” or Ambras syndrome, and it affects as few as one in a billion people; and in fact, only 50 cases have been documented since the Middle Ages.

People with hypertrichosis have excessive hair on the shoulders, face, and ears. Studies have implicated it to a rearrangement of chromosome 8. It happens due to a disruption of the “crosstalk” between the epidermis and the dermis as hair follicles form in the 3-month fetus at the eyebrows and down to the toes. Normally, signals from the dermis send the messages to form follicles. As a follicle forms, it sends signals to prevent the area around it from also becoming a follicle, which results in the equal spacing of our five million or so follicles. Most of our body parts ignore the messages to form follicles, which explains why most of us are relatively hairless.

4. Epidermodysplasia Verruciformis

10 Unusual Genetic Mutations in Humans

Epidermodysplasia verruciformis is an extremely rare disorder that makes people prone to widespread human papillomavirus (HPV) infection. This infection causes scaly macules and papules (cutaneous squamous cell carcinomas) to grow on the hands, feet, and even face. These skin “eruptions” appear as wart-like lesions — and even wood-like and horn-like growths — with reddish-brown pigmented plaques. Typically, the skin tumors start to emerge in people between the age of 20 and 40, and the growths tend to appear on areas exposed to the sun. Also called Lewandowsky-Lutz dysplasia, there is no known cure, though treatments to scale back the growths are possible.

The disorder was brought to the public’s attention in November 2007 when a video of a 34-year-old Indonesian man named Dede Koswara appeared on the internet. In 2008, he underwent surgery to have 13 pounds (6 kg) of the warts removed. After the lesions and horns were extracted from his hands, head, torso, and feet, his hands were grafted with new skin. In all, about 95% of the warts were removed.

5. Severe Combined Immunodeficiency Disorder (SCID)

Also known as the Boy in the Bubble Disease, it’s a disorder in which individuals are born without an effective immune system.

10 Unusual Genetic Mutations in Humans

The disease was made famous by virtue of the 1976 film, The Boy in the Plastic Bubble, a story inspired by the lives of David Vetter and Ted deVita. In the movie, a boy is forced to live in plastic isolation for fear of exposure to unfiltered air and the introduction of life-threatening pathogens. In real life, Vetter lived in this condition for 13 years, but he died in 1984 following an unsuccessful bone marrow transplant (a failed attempt to help him fight infections).

And indeed, the disorder is caused by a number of genes, including those that cause defects in both T and B cell responses — which has a downstream negative effect on the production of lymphocytes (a type of white blood cell). SCID is also thought to arise due to the lack of adenosine deaminase (ADA). Interestingly, SCID was the first human illness treated by human gene therapy in 1990, and is increasingly being used to treat children. Image: Baylor College of Medicine Archives.

6. Lesch–Nyhan Syndrome

10 Unusual Genetic Mutations in Humans

LNS is a genetic disorder that affects one in every 380,000 births, nearly all of them boys. It results in an overproduction of uric acid — a waste product of normal chemical processes that’s found in blood and urine. But individuals with Lesch-Nyhan release excess uric acid through their blood which builds up under the skin causing gouty arthritis. It can also cause kidney and bladder stones.

The disease also affects neurological function and behavior. Individuals exhibit involuntary body movements, like tensing muscles, jerking movements, and flailing limbs. Self-mutilating behaviors are also common, including head banging, and lip and finger biting. Individuals can be given allopurinol to help with the gout, but treatments for the neurological and behavioral aspects of the disease remain out of reach.

7. Ectrodactyly

Formerly known as “lobster claw hand, ”individuals with this disorder have a cleft where the middle finger or toe should be. These split-hand/split-foot malformations are rare limb deformities which can manifest in any number of ways, including cases including only the thumb and one finger (typically the little finger or little finger). It’s also associated with hearing loss. Genetically speaking, it’s caused by several factors, including deletions, translocations, and inversions in chromosome 7.

10 Unusual Genetic Mutations in Humans

A 2007 ABC article featured Bree Walker, a television anchorwoman living in Los Angeles who lives with the disease. Walker also appeared on the television show “Nip/Tuck” as a character with ectrodactyly who helps a family with the disorder. Thankfully, surgical procedures can correct some of these malformations.

8. Proteus Syndrome

10 Unusual Genetic Mutations in Humans

In conjunction with neurofibromatosis type I, this is the disease that likely afflicted Joseph Merrick, the so-called Elephant Man. It’s a condition in which bones, skin, and other tissues are overgrown. Individuals typically have organs and tissues that grow out of proportion with the rest of their body, and because the overgrowth varies and exhibits no apparent order, it can result in strange and imbalanced features. Signs of the disorder don’t usually appear until about 6 to 18 months after birth. The severity of proteus syndrome varies from individual to individual, and it occurs in less than one in one million people. And in fact, only a few hundred documented cases have ever been reported.

The disorder results from a mutation in the AKT1 gene (which regulates cell growth), causing mosaicism; as cells grow and divide, some cells exhibit the mutation while others do not. The resulting mixture of normal and abnormal cells is what causes the overgrowth.

9. Trimethylaminuria

This genetic disorder is so rare that its rate of incidence is not even known. But it’s very obvious when someone with trimethylaminuria is standing next to you. Individuals with the condition, because they cannot break down the naturally occurring — but pungent smelling — trimethylamine, literally smell like rotting fish, rotting eggs, garbage, or urine. It’s for this reason that it’s also called the Fish Odor Syndrome. Trimethylaminuria is found in sweat, urine, exhaled breath, and other bodily secretions. But for individuals with this disorder, typically women (for unknown reasons) it shows up in abnormal amounts. The severity of the odors seem to peak just before and during menstrual periods and after taking oral contraceptives; there may be a link to female sex hormones like progesterone or estrogen.

Consequently, people with trimethylaminuria have an exceptionally difficult time in social settings. The odor can vary in intensity over time, but many people experience depression and social isolation as a result.

10. Marfan Syndrome

10 Unusual Genetic Mutations in Humans

While unusual in its manifestations, this genetic disease is fairly common. Marfan syndrome is a disorder of the connective tissues, and it appears in about one in every 10,000 to 20,000 births. Interestingly, nearsightedness (or myopia), is a common form of the disease. But it’s more renowned for the way it causes bones to overgrow and create loose joints. People with Marfan Syndrome tend to have long and thin arms and legs. Overgrown ribs can cause the chest bone to bend inward or push outward. Spinal curvature is another problem.

It’s a myth, by the way, that Lincoln had it (he probably had Multiple endocrine neoplasia type 2B). But other famous people with Marfan include Sergei Rachmaninoff, Robert Johnson, and Bradford Cox of Deerhunter/Atlas Sound fame (featured in image at left). Javier Botet, the actor who recently spooked audiences as the bendy ghost in Mama, also has Marfan syndrome.

Top illustration by appler via Shutterstock