Choroideremia is a rare inherited eye condition that causes slow vision loss over many years. It mainly affects males, usually starting in childhood or the teen years with night blindness and trouble seeing to the sides. People with choroideremia often keep central vision into adulthood, but many develop severe vision impairment later in life. There is no cure, and care focuses on low-vision aids, regular eye exams, and support for daily activities. Genetic testing can sometimes clarify why choroideremia appears in families.
Overview
ChoroideremiaSymptoms
In choroideremia, early symptoms include difficulty seeing in low light and loss of side vision. Over time, this often progresses to tunnel vision and, later, reduced central vision. Many males are affected more severely, while severity varies.
Outlook and prognosis
Many people with choroideremia notice night-vision problems in childhood or teens, with side vision gradually narrowing over decades. Central vision often lasts into mid or later adulthood, though rates vary within families. Regular eye exams, low-vision tools, and emerging therapies support daily life.
Causes and risk factors
Choroideremia is caused by CHM gene mutations, typically inherited on the X chromosome. Risk is highest for males and families with carriers; new mutations occur, but lifestyle or environment aren’t causes.
Genetic influences
Genetics is central in choroideremia; it’s an inherited X‑linked condition caused by changes in the CHM gene. Variants reduce REP-1 protein, leading to progressive retinal cell loss. Family history, carrier status, and sex strongly influence who is affected and how severely.
Diagnosis
Choroideremia is usually suspected from features on a dilated eye exam and retinal imaging (OCT, fundus photos) plus visual-field testing. Genetic tests confirming CHM gene changes establish the genetic diagnosis of Choroideremia. Family history and carrier testing can support diagnosis.
Treatment and drugs
Treatment for choroideremia focuses on protecting remaining vision and slowing change. Care often includes regular eye exams, low‑vision aids, sunglasses for glare, vitamin A moderation, and managing complications like cystoid macular edema. Gene therapy trials and retinal implants are emerging options through specialist centers.
Symptoms
Low-light places can become challenging, and side vision may slowly narrow. You might notice small changes at first, like needing extra time for your eyes to adjust in a dark room. Early features of choroideremia often include night vision trouble and difficulty with dark adaptation. Changes can start in childhood or the teen years and move at different speeds for different people.
Finding your way in dim or low light is hard, especially at dusk or indoors. Clinicians call this nyctalopia, which means trouble seeing when the lights are low. It often shows up early in choroideremia.
Side (peripheral) vision shrinks, making it easier to miss steps, doorframes, or people coming from the side. Over time this can feel like looking through a narrowing tunnel. Doctors can measure this with visual field testing.
Moving from bright sunlight into a darker room, the eyes take longer to adjust. You may pause or need guidance while your vision catches up. This is a common early feature in choroideremia.
Bright lights or oncoming headlights can feel harsh and wash out detail. Sunglasses, caps, or anti-glare lenses may help reduce discomfort. People with choroideremia often find nighttime driving especially difficult.
How people usually first notice Choroideremia?
People often first notice choroideremia as trouble seeing in the dark or in dim rooms, usually starting in childhood or the teen years, with night blindness standing out long before daytime vision changes. Over time, many realize their side vision is narrowing, making it harder to notice things off to the edges and causing more bumps or stumbles in low light, which leads to an eye exam. An ophthalmologist may confirm the first signs of choroideremia with tests that show thinning of the retina and choroid and an X‑linked inheritance pattern, often after similar symptoms are recognized in male relatives.
Types of Choroideremia
Choroideremia is a rare inherited eye condition that mainly affects the light-sensing layer and support tissue at the back of the eye. It has a single genetic cause—changes in the CHM gene—but people can experience a range of severity based on the specific variant and who is affected. Symptoms don’t always look the same for everyone. Clinicians often describe them in these categories:
Classic X-linked
The typical form linked to CHM gene changes on the X chromosome. Most males develop night blindness in childhood and gradual tunnel vision that narrows over decades. Many keep central vision into mid-adulthood before it declines.
Female carriers
Women with one changed and one typical CHM gene may have mild or patchy changes. Some notice reduced night vision or blind spots, while others have normal vision for many years. Regular eye exams track subtle changes that may progress slowly.
Early-onset severe
Certain CHM variants can lead to faster vision loss starting in early childhood. Night blindness and side-vision loss appear sooner and central vision can decline earlier than in the classic form. Not everyone with a rare variant will follow this rapid course.
Late-onset milder
Some people develop symptoms later, with slower narrowing of side vision and longer preservation of reading vision. Changes can remain mild into midlife. These patterns often reflect differences among variants of choroideremia.
What genetics can tell you about symptoms
Some people with CHM gene changes develop night blindness first, then gradually lose side vision as retinal cells that rely on the missing REP-1 protein break down. Variants that severely reduce REP-1 function often cause earlier, faster vision loss than milder changes.
Causes and risk factors
Choroideremia is caused by a change in the CHM gene on the X chromosome, most often inherited but sometimes new in a family. It follows X-linked inheritance, so males are more likely to be affected and females may be carriers with mild effects. Some risks are modifiable (things you can change), others are non-modifiable (things you can’t). Family history and being male are not changeable, and early symptoms of choroideremia in the family often prompt genetic testing. There is no proven environmental cause, but smoking, poorly controlled diabetes, and high blood pressure can strain the retina and may affect how choroideremia progresses.
Environmental and biological risk factors
Choroideremia is present from birth and mainly influenced by biology rather than outside exposures. Doctors often group risks into internal (biological) and external (environmental). For this condition, internal factors matter far more, and environmental links have not been clearly shown. Below are the biologic and environmental elements known today.
People born male are far more likely to develop choroideremia. This relates to differences in the X and Y chromosomes. Females may have mild changes or none at all.
As men age, brand-new changes can accumulate in sperm. This very rarely can result in a child born with choroideremia. The overall chance remains low, even with older paternal age.
Older egg age mainly raises risks for conditions caused by an extra or missing chromosome, not this one. For choroideremia, any age-related effect appears small. Most cases are unrelated to maternal age.
No clear environmental cause for choroideremia has been identified. Common exposures such as air pollution, heavy metals, or medications during pregnancy have not been shown to raise risk. Research is ongoing, but no specific exposure has been confirmed.
Genetic risk factors
In many families, vision changes follow a pattern because changes in a single X-chromosome gene are passed from one generation to the next. Understanding the genetic causes of choroideremia helps families see who is at risk and who might be a carrier. Carrying a genetic change doesn’t guarantee the condition will appear. Genetic testing can confirm the CHM gene change and clarify risks for relatives.
CHM gene changes: Variants in the CHM gene disrupt a protein needed to keep the light-sensing layer and its support tissue healthy. This is the direct genetic cause of choroideremia. Testing this gene usually finds the family’s specific change.
X-linked inheritance: The CHM gene sits on the X chromosome, so the condition follows an X-linked pattern in families. Carrier mothers have a 50% chance to pass the changed gene to each child. Fathers with choroideremia pass the changed X to all daughters and to none of their sons.
Male sex: People with one X chromosome, typically males, are most likely to develop full choroideremia. They tend to have earlier and more pronounced vision changes than carrier females. Severity can vary between families.
Female carriers: Many females who carry a CHM change have no or mild symptoms. Each daughter has a 50% chance to be a carrier, and each son has a 50% chance to be affected. Eye exams and imaging can detect subtle features even when vision seems normal.
X-inactivation effects: In females, cells randomly switch off one X chromosome, which can make symptoms range from none to noticeable. Skewed inactivation can lead to patchy changes on retinal scans and, in some, real-world vision problems. This helps explain why even relatives with the same variant can have different experiences.
De novo changes: A CHM variant can appear for the first time in a family without prior history. The chance is small but real, which is why a negative family history does not rule out choroideremia. Genetic testing confirms whether a change is present.
Parental mosaicism: Rarely, a parent carries the CHM change in a portion of their egg or sperm cells but tests negative in blood. This can raise the chance of having another affected child after a seemingly new case. A genetics team can estimate this recurrence risk for the family.
Founder variants: In some families or regions, everyone with choroideremia shares the same ancestral CHM change. This founder effect can make the condition appear more often in certain communities. Ancestry clues sometimes guide testing in large family networks.
Variant type differences: Truncating or deletion changes usually stop the CHM protein from working, while some missense changes may leave limited function. Residual function can influence how fast vision changes progress, but predictions are not exact. Doctors interpret variant type alongside exam findings.
Lifestyle risk factors
Lifestyle habits do not cause choroideremia, but they can influence how quickly vision changes, how symptoms are managed, and the risk of complications like falls. Understanding lifestyle risk factors for Choroideremia can help prioritize choices that protect remaining vision and day-to-day function. Below are practical ways how lifestyle affects Choroideremia, focusing on oxidative stress, ocular blood flow, and safety.
Tobacco smoke increases oxidative stress in the retina and choroid, which can accelerate loss of photoreceptors in choroideremia. Avoiding smoking and secondhand smoke may help protect remaining vision. Vaping aerosols can also impair vascular function and are best avoided.
Chronic unprotected UV/blue light adds phototoxic stress to the retinal pigment epithelium in choroideremia. Wearing brimmed hats and UV400 or blue-filter lenses outdoors may reduce cumulative light damage. Avoid excessively dim environments that raise trip risk.
Carotenoids (lutein/zeaxanthin) and omega-3s support photoreceptor membranes and antioxidant defenses relevant to choroideremia. Eating leafy greens, colorful vegetables, and fatty fish may help maintain retinal function. Avoid restrictive diets that cause micronutrient deficits.
Frequent hyperglycemia damages retinal microvessels and adds stress to the already compromised choroidal support in choroideremia. Choosing lower-glycemic, fiber-rich meals may help protect retinal perfusion. If you have diabetes or prediabetes, tighter dietary control is especially important.
Risk prevention
Choroideremia is inherited, so there’s no way to fully prevent the condition itself right now. Prevention focuses on protecting the vision you have, avoiding eye injuries, and planning ahead for daily life as changes occur. Prevention is about lowering risk, not eliminating it completely. Knowing the early symptoms of choroideremia—like trouble seeing in dim light and shrinking side vision—can help you seek timely care and support.
Yearly visits with a retina specialist can catch treatable issues early. This helps track changes and guide practical steps to protect daily vision.
Wear UV-blocking sunglasses and a brimmed hat outdoors to reduce light stress on the retina. Consider lenses that reduce glare to make mobility safer.
Keep hallways and entryways well lit and use night-lights to reduce falls. Adjust lighting at home and work to ease strain from dim environments.
Use protective eyewear for sports, DIY projects, or jobs with flying debris. Preventing eye trauma is especially important for people with choroideremia.
Transmission
Choroideremia is not contagious; you can’t catch it or spread it through everyday contact, sex, saliva, or blood. It is inherited in an X-linked pattern, which describes how choroideremia is inherited through a gene on the X chromosome.
A mother who carries the altered gene has a 50% chance with each pregnancy to pass it on: sons who inherit it typically develop choroideremia, while daughters who inherit it usually become carriers and may have mild vision changes. A father with choroideremia passes the altered gene to all of his daughters (who become carriers) and to none of his sons. Rarely, the genetic transmission of choroideremia occurs because of a new gene change, so there may be no previous family history.
When to test your genes
Consider genetic testing if you have night blindness, peripheral vision loss, or a family history of choroideremia, especially in males or maternal relatives. Test before symptoms to confirm carrier status, clarify diagnosis from similar retinal diseases, and guide surveillance. It also informs eligibility for trials and family planning.
Diagnosis
Day to day, Choroideremia often starts as trouble seeing in dim light or losing side vision, which can make evening walks or driving at night feel challenging. Eye doctors look for a pattern of retinal changes and use imaging to map what’s affected. Getting a diagnosis is often a turning point toward answers and support. In many cases, the genetic diagnosis of Choroideremia is confirmed with a DNA test after the eye findings point strongly to this condition.
Clinicians ask about early symptoms of night blindness and gradual loss of side vision. These clues help focus testing on inherited retinal conditions.
A pattern of vision problems mainly in males on the mother’s side can suggest X‑linked inheritance. Relatives’ histories and any prior diagnoses help guide next steps.
The retina is examined for characteristic thinning and patchy atrophy starting in the periphery. Pigment changes and pale areas can help distinguish Choroideremia from other causes.
Color photos document the appearance of the retina at baseline. Comparing images over time helps track progression.
Stages of Choroideremia
Choroideremia tends to progress slowly over many years, with vision changes that shift from night difficulties to reduced side vision and, later, central vision problems. Often the process begins when you notice changes in daily life. Doctors follow recognizable stages based on symptoms and eye exam findings, even though the pace can differ from person to person. Knowing the typical pattern helps set expectations and plan check-ups.
Early changes
Early symptoms of choroideremia may be subtle, like trouble adjusting from bright to dim rooms. Eye exams may show faint patches in the retina before vision tests change. Females who carry the gene may show mild or uneven changes.
Night blindness
Difficulty seeing in low light becomes clear at night or in dark restaurants. You may need extra time for your eyes to adapt after lights go out.
Peripheral narrowing
Side vision gradually shrinks, making bumping into doorframes or missing steps more common. Visual field tests show a ring of loss spreading inward.
Central island
Central vision often remains sharp for years, leaving a small island of sight. Reading and recognizing faces can still be possible but require good lighting and high contrast.
Late stage
The central island becomes very small and fine detail fades. Many people with choroideremia rely on magnifiers, mobility training, and support services at this point.
Outlook and prognosis
Looking ahead can feel daunting, but most people with choroideremia notice changes unfold slowly over decades. Night blindness is often an early symptom of choroideremia, followed by a gradual narrowing of side vision that can make driving at night or navigating dim hallways difficult. The central spot used for reading and recognizing faces is usually preserved until mid-to-late adulthood, so many continue work, school, and family life with adjustments like brighter lighting and contrast tools. Everyone’s journey looks a little different.
Understanding the prognosis can guide planning and day-to-day choices. Vision loss typically progresses, but the pace varies even within the same family; some people retain useful central vision into their 50s or 60s, while others need low-vision aids earlier. Choroideremia mainly affects the eyes and does not shorten life expectancy, so mortality is similar to the general population. In medical terms, the long-term outlook is often shaped by both genetics and lifestyle, including protecting eyes from injury, managing glare, and using vision rehab early.
Over time, most people with choroideremia benefit from regular eye exams, low-vision services, mobility training, and practical tools like magnifiers or text-to-speech. Genetic testing can sometimes provide more insight into prognosis, especially when planning for clinical trials or family decisions. Talk with your doctor about what your personal outlook might look like.
Long-term effects
Choroideremia is a lifelong, inherited eye condition that gradually narrows the visual world. Many notice trouble seeing at night first, then difficulty with side vision that can affect driving, navigating dim rooms, or walking outdoors after sunset. Long-term effects vary widely, and changes can progress at different speeds even within the same family. Over time, daily routines may shift as reading, mobility, and work or school tasks need more light or visual aids.
Early symptoms of choroideremia often include trouble seeing in low light. Dim restaurants, movie theaters, or dusk can become challenging. This tends to appear in childhood or the teen years.
Side vision gradually shrinks in choroideremia. People may bump into door frames or miss a curb they didn’t see off to the side. This field loss usually progresses over decades.
As the visual field narrows, vision can feel like looking through a tube. Navigating crowds or crossing streets may become harder. Doctors often describe these as long-term effects or chronic outcomes.
Reading small print or recognizing faces can become difficult later in choroideremia. Central vision often holds on for years, then declines as the disease advances. Many still retain some light perception even in late stages.
How is it to live with Choroideremia?
Living with choroideremia often means adapting to slowly changing vision—night blindness and trouble seeing to the sides come first, while reading and central vision can remain useful for many years. Daily life may involve brighter lighting, high-contrast labels, magnification tools, and careful route planning, plus giving yourself extra time in dim spaces or unfamiliar environments. For family and friends, small adjustments—like announcing your presence, keeping walkways clear, offering a steady arm in low light, and following the person’s lead—can make shared activities easier and safer. Many find that low-vision rehabilitation, orientation and mobility training, and connection with others facing similar changes help maintain independence, confidence, and a full, engaged life.
Treatment and drugs
Choroideremia treatment focuses on protecting vision, managing day-to-day symptoms, and monitoring for changes over time. There’s no widely available cure yet, but regular eye checkups, low-vision aids (like high-contrast lighting, magnifiers, and digital tools), and practical adjustments at home and work can help many people stay independent. Research is ongoing into gene therapy and other approaches; some clinical trials have shown promise for stabilizing or improving vision in select cases, but access is limited and long-term results are still being studied. Alongside medical treatment, lifestyle choices play a role, including using sunglasses to reduce UV exposure, keeping conditions like diabetes and high blood pressure under control, and avoiding smoking. Ask your doctor about the best starting point for you, and whether referral to a low-vision specialist or discussion about clinical trials makes sense in your situation.
Non-drug treatment
Living with Choroideremia often means adapting to gradual changes in night and side vision while protecting the eyesight you have. Beyond prescriptions, supportive therapies can help you stay independent and safe as vision changes. Early, practical steps—at home, at work, and when moving around—tend to make the biggest difference day to day. Recognizing early symptoms of Choroideremia, like trouble seeing at night or losing side vision, can guide timely low-vision support.
Specialists teach ways to make the most of remaining sight using lighting, contrast, and visual strategies. They also match tools to your needs and train you to use them confidently. This is a cornerstone of living well with Choroideremia.
Training builds safe travel skills indoors and outdoors, including white cane techniques if helpful. You practice route planning, crossing streets, and using public transport. This can reduce falls and boost confidence.
Devices like electronic magnifiers, large-print settings, screen readers, and voice assistants can keep reading, work, and hobbies accessible. Apps can help with navigation, money identification, or object recognition. Your low-vision team can tailor choices as vision changes.
Brighter, focused task lighting and high-contrast labels make cooking, reading, and crafts easier. Glare control with matte finishes and tinted lenses can sharpen comfort and clarity. Simple changes in bulb type and lamp placement often help a lot.
Your genes may have an impact on how drugs work for you
Some medicines for choroideremia or its symptoms can act differently depending on gene changes that affect how your body processes drugs or how retina cells respond. Pharmacogenetic testing, when available, may guide safer doses and reduce side effects.
Pharmacological treatments
There is no cure yet for choroideremia, but medicines can help treat complications that threaten central vision—mainly swelling at the macula or abnormal blood vessels. These medicines don’t reverse early symptoms of choroideremia, but they may help stabilize or improve how clearly you see by reducing fluid or stopping leakage. Beyond standard options, ongoing clinical research is bringing new drug therapies into trials. Availability varies by country, and your eye specialist will tailor choices to your eye’s findings on exam and scans.
These carbonic anhydrase inhibitor eye drops can reduce macular swelling (fluid) that sometimes occurs in choroideremia. Some people notice sharper central vision or less distortion, while others mainly see stability.
This pill can dry excess fluid in the macula and may improve contrast or reading vision in choroideremia. Tingling in fingers, frequent urination, or taste changes can occur, so dosing is individualized.
Ranibizumab, aflibercept, or bevacizumab are injected into the eye if choroidal neovascularization (leaky new vessels) develops in choroideremia. Treatments are usually given in a series and can protect central vision by stopping leakage.
Photodynamic therapy with verteporfin may be considered when injections are not suitable for choroidal neovascularization. It uses a light-activated drug to seal abnormal vessels and is decided case by case.
Genetic influences
Most cases are caused by a change in a gene on the X chromosome (called CHM) that interferes with the upkeep of the retina and its supporting layer. Because this gene sits on the X chromosome, choroideremia most often affects males, while females who carry the gene change may have no symptoms or only mild vision changes. In families, the pattern often shows affected sons and maternal uncles, with women in the maternal line more likely to be carriers. DNA testing can sometimes identify these changes. Test results can confirm the diagnosis, explain why early symptoms of choroideremia tend to appear in childhood or the teen years, and guide which relatives might consider an eye exam or genetic counseling. Even within the same family, the pace of vision changes can vary, and some female carriers develop night-vision difficulties later in life.
Is Choroideremia genetic?
Genetics is central in choroideremia; it’s an inherited X‑linked condition caused by changes in the CHM gene. Variants reduce REP-1 protein, leading to progressive retinal cell loss. Family history, carrier status, and sex strongly influence who is affected and how severely.
Pharmacogenetics—how genetics influence drug effects
In choroideremia, the inherited change that causes the condition often guides treatment planning, because emerging therapies aim to restore the missing gene function in the retina. Gene therapy studies deliver a working copy of the CHM gene (the gene linked to choroideremia) to eye cells, so eligibility usually depends on a confirmed CHM change and enough remaining retinal tissue—not on the common genes that affect how your liver handles medicine. There’s no approved drug treatment for choroideremia yet in the US or EU, but genetics already shapes who can join studies and will likely guide how care teams time and tailor future gene‑based options. Doctors can use your genetic information to confirm the diagnosis, counsel family members, and discuss whether a gene therapy study could be a good fit. Outside of gene therapy, your genes can still matter for medicines used around eye procedures—such as pain relievers, anesthetics, or certain antibiotics—because common differences in drug‑processing enzymes may change dose needs or side‑effect risk. Share any prior pharmacogenetic test results with your eye specialist and anesthesia team, and ask whether any of your current prescriptions might benefit from dose adjustments.
Interactions with other conditions
Living with choroideremia alongside other eye or health problems can compound vision challenges. Doctors call it a “comorbidity” when two conditions occur together. Common issues like cataracts, glaucoma, or diabetic retinopathy may add blur, glare, or pressure-related damage on top of the side-vision loss from choroideremia, making daily tasks in dim settings especially tough. Early symptoms of choroideremia—trouble seeing at night and narrowing peripheral vision—can also be confused with other retinal conditions such as retinitis pigmentosa, or hidden by severe nearsightedness or diabetes-related changes, so a careful dilated eye exam helps sort out what’s driving changes in sight. Swelling in the central retina (macular swelling), which can appear in some inherited retinal diseases or after eye surgery, may temporarily reduce sharpness but is often treatable if caught early. Medications for other conditions usually don’t conflict with choroideremia care, but long-term steroid use can raise eye pressure and some drugs can affect the retina, so coordinating treatment plans across your eye doctor and medical team is important.
How genes can cause diseases
Humans have more than 20,000 genes, each carrying out one or a few specific functions in the body. One gene instructs the body to digest lactose from milk, another tells the body how to build strong bones and another prevents the body's cells from beginning to multiply uncontrollably and developing into cancer. As all of these genes combined are the building instructions for our body, a defect in one of these genes can have severe health consequences.
Through decades of genetic research, we know the genetic code of any healthy/functional human gene. We have also identified that in certain positions on a gene, some individuals may have a different genetic letter from the one you have. We call these hotspots "Genetic Variations" or "Variants" in short. In many cases, studies have been able to show that having the genetic letter "G" in the position makes you healthy, but having the letter "A" in the same position disrupts the gene function and causes a disease. Genopedia allows you to view these variants in genes and summarizes all that we know from scientific research, which genetic letters (Genotype) have good or bad consequences on your health or on your traits.
History
Throughout history, people have described families in which several men slowly lost night vision and, over time, central sight. A grandfather stopped driving at dusk; a nephew needed brighter lights to read. Women in the same family often noticed nothing or only mild trouble in dim rooms. These patterns were noted long before modern testing could explain why.
First described in the medical literature as “choroideremia” in the late 19th century, it was initially recognized by the way the back of the eye looked during an exam and by its steady, lifelong course. Early doctors drew detailed sketches of the retina and the choroid, the layer that feeds the retina, showing areas that seemed to fade away from the edges inward. Over time, descriptions became clearer: boys developed night blindness in childhood or the teen years, then their side vision narrowed, and later central vision was affected.
With each decade, clinicians refined how they identified choroideremia, separating it from other conditions that also cause night blindness and tunnel vision, such as retinitis pigmentosa. Careful family histories revealed a consistent inheritance pattern in many lineages: mostly males affected, with women as carriers who might show subtle changes. This helped distinguish the condition even when tests were limited to what could be seen with an ophthalmoscope.
Advances in genetics in the late 20th century confirmed the X‑linked pattern and, later, pinpointed changes in a specific gene now known to be involved in the health and maintenance of light‑sensing cells. DNA research now explains how missing or altered instructions in this gene lead to the slow loss of support tissue and photoreceptors, matching what ophthalmologists had observed for generations. Identifying the gene made earlier diagnosis possible through genetic testing, even before obvious vision loss.
In recent decades, awareness has grown as patient registries, better imaging, and family screening have brought more people with choroideremia into follow‑up. What was once considered rare in clinics that relied on late-stage symptoms is now recognized more readily, including in women with milder changes. This shift has also opened the door to clinical trials exploring gene therapy and other approaches, building hope alongside careful, long-term observation.
Looking back helps explain why definitions have shifted: similar symptoms once blurred the lines between different retinal conditions. Despite evolving definitions, the core story of choroideremia has stayed the same—slowly changing vision across a lifetime, strong family patterns, and steady progress from bedside observation to molecular understanding.