Werner Syndrome Handbook
A Guide for People with Werner Syndrome, Their Family and
Healthcare Professionals

1st Edition

Table of contents❶ What is Werner syndrome?..............p1❻ Infection……………………..…p6❷ Things to be aware of in life…..p2❼ Eye disease………………..….p7❸ D i a b e t e s …………………………..p3❽ Sarcopenia and osteoporosis……..p8❹ Dyslipidemia…………………….p4❾ Foot ulcers (hard-to-heal wounds)….p10❺ F a t t y l i v e r .……………………....p5➓ Tumor……………………………….. …..p13

Clinical manifestations ofWerner syndrome

Hair conditions
Gray hair
Baldness
Voice conditions
High-pitched hoarse
voice

Liver disease
Fatty liver (p5)Muscle and bone
symptoms
Sarcopenia (p8)Osteoporosis (p8)Tumor (p13)

Eye disease
Cataract (p7)Heart disease
Arteriosclerosis
Angina pectoris
Myocardial infarction
Abnormalmetabolism
Visceral fat
accumulation
Diabetes (p3)
Dyslipidemia (p4)Foot symptoms
Skin ulcer (p6 and p10)
Peripheral arterial disease

１

What is Werner syndrome?

Werner syndrome is said to be a disease of "premature aging" = a progeroid syndrome
because aging seems to progress rapidly after puberty. The patient looks older than theiractual age.
People with Werner syndrome starts to develop
symptoms such as gray hair/hair loss, cataracts inboth eyes, and a high-pitched hoarse voice intheir 30s. In addition, muscle atrophy in thearms and legs, formation of calluses due to skinhardening, and hard-to-heal foot/elbow wounds(intractable skin ulcers) may be observed. Patientsusually have short stature, and X-rays may
reveal subcutaneous calcification (accumulationof calcium components) of the Achilles
tendons and subcutaneous tissue.

Main Symptomms

Cataracts in both eyes

Diabetes and dyslipidemia (abnormal cholesterol
and triglyceride levels) are also common among
these patients. Therefore, they are at risk ofdeveloping arteriosclerosis and cancer; hence,
careful follow-up is required. Skin care isnecessary as repeated infections from ulcers cancause bacteria to enter the bone marrow.
The number of Werner syndrome patients in Japan is estimated to be 700~2,000. The disease is prevalent inJapan, with 60% of the patients reported worldwide being Japanese. In the past, most of the reported cases
were from areas with many consanguineous marriages, which leads to closely related kinship; in recent years,
the number of patients whose disease is not related to consanguinity is dramatically increasing. Lifestyle
habits such as daily diet and exercise are unrelated to the onset of this disease.
Werner syndrome is caused by an abnormality in the WRN gene. The disease only occurs when both WRN
genes are defective. Each of the patient’s parents only has one causative gene and does not develop thedisease. About 1 in 4 of the patient’s siblings will develop the disease; however, the probability that thepatient’s children or their children will develop the disease like their parent or grandparent is extremely
low.
There is no fundamental cure for Werner syndrome. However, early detection and treatment are importantfor diseases such as cancer, cataracts, diabetes, dyslipidemia, etc., because surgery and medications are
effective and they improve the patients’ prognosis.
In the past, many patients died from cancer and arteriosclerotic diseases such as myocardial infarction in
their mid-40s. However, a recent study shows that the average life expectancy has increased by more than
10 years, and the number of Werner syndrome patients in their 60s is significantly increasing: the oldest
patient was aged 77 years.

2

Things to be aware of in life

Prevention and treatment of visceral fat obesity, diabetes, and dyslipidemia
Excessive carbohydrate and fat intake should be avoided as fat tends to accumulate in the abdomen(visceral obesity), thus increasing the susceptibility to diabetes and dyslipidemia. Exercise should be
performed regularly. Treatment for general type 2 diabetes is recommended to manage diabetes;
medications that improve the sensitivity to insulin, a hormone that lowers the blood sugar levels, are also
used in many cases as the primary cause of Werner syndrome is decreased sensitivity to insulin.
Dyslipidemia is managed based on the treatment used for general dyslipidemia,
and low-density lipoprotein (LDL) cholesterol-lowering drugs called statins
are often used. Hypertension is treated by avoiding excessive salt intake andusing general antihypertensive drugs as needed. Good control of theserisk factors suppresses the progression of arteriosclerosis and prevents
myocardial infarction.

Prevention of sarcopenia (muscle wasting)Protein-rich foods such as soy products, fish, and meat should be consumed. Amino acid supplements
for leucine are said to be effective in preventing general sarcopenia and may also be effective for Werner
syndrome patient.

Prevention of Osteoporosis
Consumption of foods containing vitamin D, calcium intake
are recommended to prevent osteoporosis.
Calcium intake

Foods containing vitamin D

Prevention/treatment of skin wounds (intractable ulcers)
It is important to prevent foot blisters by choosing well-fitting shoes as foot wounds take long to heal

and greatly interfere with daily life. Thin and tough skin can break or tear easily due to the pressure
applied by the underlying bones. Such wounds are at risk of developing into deep ulcers. Special shoes(orthoses) may be used to protect areas with high pressure or that will likely develop into wounds. Areas
prone to ulcers such as the Achilles tendon, heels, feet, and elbows should be protected and assessed ona daily basis. If ulcers form, symptomatic treatment such as cleaning, disinfection, protection, andmoisture retention is the primary treatment. However, surgery to graft skin from other areas of the bodymay be effective in some cases.

Early Detection of Cancer
Early detection and treatment are important because cancer develops more
often than usual. Therefore, undergoing regular cancer screening is recommended.

Diabetes
What is diabetes?
Main symptoms

Diabetes is a disease that occurs when the insulinlevels are low or the insulin is ineffective,
resulting in high blood sugar levels (glucose
concentration in the blood).

Recently, my mouth is dry

Symptoms including “recently, my mouth is dry”; “I
go to the bathroom more often and pee more”; and “I
get tired easily” may appear. Meanwhile, other
patients may remain asymptomatic.
What is alarming about diabetes is that other diseases
may develop if it is left untreated.
In addition to problems such as “blindness,”“accumulation of waste products in the body due tothe inability to urinate properly (uremia),”and“rotting of the foot,” it increases the risk of heartdisease, stroke, and even cancer and dementia.

I go to the bathroom more often
and pee more

I get tired easily.

ventralDiabetes and Werner ventral
syndrome
According to a previous survey conducted inJapan, 60% of patients with Werner syndrome,
regardless of gender, develop diabetes as acomplication. One of the causes is fat
accumulation around the abdomen, which
contributes to the patient’s metabolic
syndrome appearance. As a result, sensitivity
to insulin decreases.

ventralventral

right

left

dorsalVisceral fat/subcutaneous fat
Computed tomography scan: the purple-colored area indicatesvisceral fat.

Treatment for diabetes
The intake of snacks and juice drinks should be limited.
Eating until 70%–80% full is highly encouraged.
Performing various exercises as tolerated (exercises using
plastic bottles, etc.) are effective. Metformin andpioglitazone are known to be effective. Recently, incretinrelated drugs have also been shown to be effective.

Dyslipidemia
Dyslipidemia and arteriosclerosis
Lipids flowing in the blood

Fats (lipids) such as cholesterol and triglycerides

circulate freely in the blood.
Cholesterol is further divided into bad cholesterol(LDL-C) and good cholesterol (high-density
lipoprotein cholesterol [HDL-C]). When the LDL-C
or triglyceride levels are higher than the standard
value or when the HDL-C levels are lower than thestandard value, it is referred to as dyslipidemia.
Dyslipidemia increases the likelihood of developing
arteriosclerosis and is a risk factor for heart diseases,
such as angina pectoris and myocardial infarction,and stroke.

Cholesterol
Bad cholesterol (LDLcholesterol: LDL-C)
Good cholesterol (HDL
cholesterol: HDL-C)

Triglycerides

When the LDL-C or triglyceride
levels are higher than the standard
value or when the HDL-C levels arelower than the standard value, it isreferred to as dyslipidemia.

Dyslipidemia, arteriosclerosis, and Werner syndrome
According to a previous survey conducted in Japan, halfof Werner syndrome patients develop dyslipidemia(70% with high LDL-C levels, 80% withhypertriglyceridemia, and 30% with low HDL-C
levels).
Similar to diabetes, patients develop a metabolic
syndrome appearance, leading to insensitivity toinsulin, which is believed to be one of the causes ofdyslipidemia. Although angina pectoris and myocardial
infarction commonly develop in people with Werner
syndrome compared with that in the general population,
the incidence of stroke is relatively low.

About half of the patients havedyslipidemia as a complication❶ Arterial wall thickens

Arteriosclerosis❸ Formation of bloodclots❷ Fat accumulation on the wall
❹ Clogging of the blood vessel

Treatment for dyslipidemia
Lifestyle modification, limited animal fat intake, and standard treatment such as the administration of
statin drugs are used to prevent arteriosclerosis.

Fatty l iver
About fatty liver
Fatty liver is defined as an abnormal accumulationof triglycerides, a type of lipid, in the liver.
Alcoholic fatty liver due to alcohol consumption iswell known; recently, non-alcoholic fatty liver, inwhich fat accumulates in the liver even with low
alcohol consumption, is drawing attention.

Alcoholic fatty liver
due to alcohol
consumption

Both may progress to diseases such as cirrhosis andliver cancer.
Non-alcoholic fatty liver
Fat accumulation in the liver
despite low alcohol
consumption

Fatty
liver
Abnormalaccumulation of
triglycerides

Fatty liver and Werner syndrome
Approximately 30% of patients with Werner syndrome
develop fatty liver.

Dark areas indicate fat accumulation.
(Usually appears as bright white)

In general, non-alcoholic fatty liver is more common inobese people, whereas Werner syndrome patients develop
fatty liver even if their body weight is significantly below
normal.
No study has reported that cirrhosis or liver cancer iscommon in Werner syndrome patients with fatty liver.
Advanced fatty liver is visible
Abdominal computed tomography scan

Treatment for dyslipidemia
Fatty liver has no specific cure.
A previous study reported that the fatty liver in a Werner syndrome patient improved with the useof astaxanthin.

Inf ectio n
Infection of skin ulcers
Werner syndrome patients are prone to skin disorders and tend to develop corns (clavuses) on thesoles of the feet. The skin surface where the corn is located becomes inflamed and collapses, often
resulting in deep ulcers. This also occurs frequently in patients with diabetes. Since Werner
syndrome is often complicated by diabetes, patients with this syndrome are prone to developing
plantar ulcers. The ulcers develop not only on the soles of the feet but also on the knees and elbows.
Foot care is of utmost importance.
Aboid developing corns
Patients should avoid developing corns.
If you develop corns
Otherwise, immediate medical advice should
be sought. The attending physician should be
consulted immediately if the skin becomes gouged
and if an ulcer is suspected. At this point, the ulcer
is not yet infected.

Consult a doctor
immediately

The ulcer may be infected if thesurrounding area becomes red andswollen, feels hot, or is painful. In suchcases, treatment is required.
The ulcer can be treated with oral antimicrobial drugs if the red and swollen area (redness)surrounding the ulcer measures 2 cm in diameter, although the depth of the ulcer should also be taken
into consideration. In such case, the treatment will generally take two to four weeks. However, thepossibility of undergoing intravenous antimicrobial treatment is relatively high if the inflamed area is
not within 2 cm from the ulcer or the ulcer is deep. Hospitalization is often required in such cases,
and treatment will generally take two to four weeks. The doctor may decide to switch to oral
medication administration upon completion of intravenous treatment.
Not only the skin and subcutaneous tissue but also the joints and bones may also become infected as
the ulcer extends more deeply. Such cases are called arthritis or osteomyelitis. If this occurs,
hospitalization and treatment with intravenous antimicrobials are required. Surgical excision is often
necessary if antimicrobials alone do not alleviate the infection. In general, the treatment period willtake at least 4 weeks if the joints and bones are infected.
If repeated infection occurs, an infection caused by bacteria that are resistant to antimicrobials(resistant bacteria) is suspected. Intravenous treatment is necessary in such cases even if the infection
is mild as it may not be possible to it treat with oral medications.

Other infections to look out for
Various infectious diseases can be prevented with vaccines such as pneumonia andinfluenza. Immediate consultation with a doctor and vaccination are recommended.

Patients with Werner syndrome, also known as “progeria,” experience
premature aging. The eyes are no exception and tend to develop agerelated conditions. The most common eye condition associated withaging is cataract. Werner syndrome patients develop cataracts as earlyas 20 years old. On average, they develop cataracts at the age of 30 years.
Approximately 10% of the general population develops cataracts at theage of 50 years, and more than 80% by the age of 70 years. By contrast,
100% of Werner syndrome patients develop cataracts. Hence, somepatients are diagnosed with Werner syndrome after developing cataracts.
A cataract is a disease in which the lens becomescloudy and vision is reduced. Its symptoms include
reduced vision, glare, and blurred vision. Initial
symptoms may not only include decreased vision
but also sensitivity to headlights at night.
Myopia may also worsen as the cataracts progress.
The diagnosis can be easily made by a slit lamp
examination, which is commonly used in
ophthalmology clinics, and a general practitioner
can make the diagnosis. However, as early-onset
cataracts have various causes, Werner syndrome
will not be suspected based solely on these findings.
However, as a general rule, Werner syndrome issuspected if bilateral nuclear cataracts are observed
at a young age as cataracts in Werner syndrome
patients are characterized by opacity and hardeningof the center (nucleus) at a younger-than-averageage.

Main symptoms
Reduced vision

Sensitivity to headlights
at night

Glare/Blurring

Cataracts can be treated with small-incision (2–3 mm incision) lens reconstruction without serious
complications.
Phacoemulsification and aspiration are generally used to ultrasonically break up and suck out the
turbidity. An artificial lens is placed into the remaining pouch (lens capsule). In the case of Werner
syndrome, the hardened nucleus, which is observed in many patients, tends to pose challenges during
surgery. That said, serious complications such as incomplete wound closure do not occur as the incision
wound is smaller compared with that in previous surgical procedures.
One characteristic postoperative complication that may occur is cystoid macular edema (swelling in themacula, the most important part of the retina, which causes symptoms such as blurred and distorted
vision). It improves with eyedrops alone in patients with cataract alone, thanks to advances inpostoperative eyedrops. However, care must be taken with Werner syndrome, as cystoid macular edema
may become intractable and lead to permanent vision loss. It is generally caused by inflammation, but thefactor that triggers the onset of cystoid macular edema in Werner syndrome patients remains unknown.
Therefore, the exact incidence is unknown, but it does not seem to be common. Overall, cataract surgery
can be safely performed on Werner syndrome patients, thanks to advances in cataract surgery techniques.

Sarcopenia and osteoporosis
What is sarcopenia
Sarcopenia is a condition characterized by reduction ofmuscle mass with age, and decrease in muscle
strength and walking speed.

Main symptoms
Decreased muscle mass
with age

Sarcopenia may require long-term care in the future
and cause some difficulties in daily life. In otherwords, sarcopenia prevents an individual from living along and healthy life.
The muscle mass of the hands and feet start todecrease at a relatively young age (below theage of 40 years) in Werner syndrome patients.
Although the cause is unclear, it may be attributed to thepatient’s limited mobility due to the presence ofcontractures (impaired joint movement) and skinulcers on the soles of the feet, which are common
among Werner syndrome patients.

Decreased muscle strength andphysical function

In fact, some Werner syndrome patients who engage in habitual resistance exercise (exercise that puts aload on the muscles, so-called muscle training) do not experience a reduction in the skeletal muscle mass.
As such, sarcopenia may be preventable by performing appropriate exercise.

Prevention
Resistance exercise that is
not too taxing on the soles
and Achilles tendons

Engaging in resistance exercise that does not put
too much strain on the soles of your feet and theAchilles tendons is recommended, and sufficient
protein (ingredients for muscle) intake is highly
encouraged.
Each meal should contain at least 25g of protein.
However, if chronic kidney disease and other diseases
develop, a family doctor should be consulted.
Sufficient protein
intake8What in osteoporosis
Osteoporosis is a disease in which the bone massdecreases with age, making the bones brittle and prone tofractures.

Main symptoms

Bone become brittle,

Osteoporosis is also a dangerous condition that may affect anindividual’s life expectancy as fractures can interfere with daily
life and increase the probability of becoming bedridden.
Patients with Werner syndrome are prone to osteoporosis
at a young age.
Although it depends on the patient’s age, a previous
Japanese survey reported osteoporosis in 41% ofWerner syndrome patients, while an overseas study
reported osteoporosis in >90% of patients. In patientswith Werner syndrome, osteoporosis is more severein the lower limbs than that in the vertebrae (spine).

thus increasing therisk of farctures

Interferes with daily life or
may increase the probabilityof becoming bedridden

Prevention and treatment
Conventional osteoporosis medications can be used for treatment.
Similar to sarcopenia, performing exercises is one of the preventive measures. Vitamin D intake
promotes the absorption of calcium from food and is important for the prevention of osteoporosis. As
with sarcopenia, adequate dietary protein intake is also important.
Exercise is important for the prevention of both sarcopenia and osteoporosis. It is important to avoid
excessive exercise and incorporate exercise that is not too taxing since some Werner syndrome patientsare prone to developing ulcers on the soles of their feet and some have joint contracture.

9Foot ulcers (hard-to-heal wounds)
Werner syndrome causes hard-to-heal wounds on the skin. The most common areas are theelbows and below the knees.

Hard-to-heal wounds onthe elbow form on thelateral protruding
portion of the elbow(olecranon).
If the wound may be
extended to the elbow withthin skin, you need toconsult the dermatologist

Olecranon

The areas where hard-to-heal wounds are likely to form include the Achilles tendon,
ankles, heels, soles, inner side of the big toe, and outer side of the small toe.
The wound may extend deeply into the joint or bone because the skin is thin.

Outer side of
the big toe
Ankle

AchillestendonInner side of
the big toe

heel

10

Sole

Prevention
Prevention is important because once a woundforms, it is difficult to heal. Moistureretention and avoiding pressure areimportant. A callus may form as a sign ofpressure. The callus should be treated as theskin will be pressed further and a wound will
possibly form if it is left unattended. Wellfitting shoes should be worn to prevent theformation of calluses.

Moistureretention

Avoidingpressure

Treatment
Bacteria may accumulate inside the hard-to-healwounds. They should be removed to reduce the risk of
spread. The tissues infected with bacteria should also be
removed. Surgery may be performed to close thewounds that do not heal easily.

Prevention and treatment of intractable ulcers
One of the characteristics of Werner syndrome is thatwounds easily form on the skin (ulcers) and are
hard to heal. Wounds frequently develop in theweight-bearing part of the sole of the foot. In
addition, they are common in areas wherepressure is likely to be applied such as the Achilles
tendon, ankle joint, and elbow joint.
The wounds are difficult to heal in these areas
because the skin has thickened/toughened and theamount of fat is relatively low. It is as if the cushion
has been removed, and the bone comes in directcontact.
Moreover, poor blood flow due to narrowing of theblood vessels, calcium oxide formation in the skin,and deformation of the joints are also thought to cause
ulcer formation.

11

The callus should be treated as the skin will be pressed further and a wound will
possibly form if it is left unattended. Well-fitting shoes should be worn to preventthe formation of calluses. Prevention is important because once a wound forms, it isdifficult to heal. Moisture retention and avoiding pressure are important. A callus may
form as a sign of pressure.
Well-fitting shoes should beworn to prevent the formation of“blisters”

An insole should be inserted
to keep the weight fromconcentrating in one area.

The soles of the feet, Achilles tendons, and elbows should beassessed for presence of scratches, calluses, and corns. An
ointment or plaster (various dead-skin-softening topical agents
containing urea) that softens dead skin should be applied as soon
as possible if thickened dead skin such as calluses or corns begin
to form. Dead-skin-softening topical agents and plasters are soldat pharmacies, but a specialist such as a dermatologist should be
consulted first. Scissors are used in some cases to remove calluses
and corns that do not come off with ointment or plasters alone.
However, a specialist such as a dermatologist should be consulted
as doing so on your own may lead to wound formation.

The areas where the bone
protrudes and that are prone
to wound development
should be protected with special
orthoses(shoes).

Checklist
Any wounds, calluses,
or corns?
□□

Sole of the footAchilles tendon□ Elbow, etc.

If a callus or corn is left unattended, a wound will form in the center and will take a long time to heal.
Care must be taken to prevent bacterial infection if a wound forms. It should be kept clean by washingit with soap every day. Ointment should be applied for wound healing after rinsing thoroughly.
If necrotic areas are noted, a drug that dissolves themshould be used. If red granulation occurs, anappropriate medication should be applied to further
raise the granulation tissue and eventually reduce thewound size. If bacterial infection occurs, disinfectants,
ointments that suppress infection, and oral antibiotics
are needed. If bacterial infection is noted or if thescratch increases in size, it will be difficult to heal;
hence, a dermatologist should be consulted as soon as
possible.

A dermatologist
should be consulted assoon as possible.
12

TumorWhat is a malignant tumor?
A malignant tumor is a tumor in which certain cells disregard the order established in the body andproliferate, spread to the surrounding tissues, or cause metastasis. Malignant tumors include epithelial
tumors (cancer), non-epithelial tumors (such as sarcoma), and blood tumors such as leukemia. In general,cancer is common, while non-epithelial tumors are rare. When the incidence of cancer and that of nonepithelial tumors are compared, the ratio is about 10 to 1.

Malignant tumors and Werner syndrome.
According to a previous survey conducted in Japan, malignant tumors were found in approximately 30%
of people with Werner syndrome. They tend to develop at a relatively young age (40 years). Nonepithelial tumors, which rarely develop, are common in Werner syndrome patients with a cancer to nonepithelial tumors ratio of 1 to 2. Among them, malignant melanoma, malignant fibrous histiocytoma,
and meningeal tumors are common. With regard to cancer, thyroid cancer is commonly observed.
Moreover, it is not uncommon for a Werner syndrome patient to develop multiple cancers (multiple
tumors), in which several comorbid malignant tumors develop. Recently, the number of cancer cases
has dramatically increased as the life expectancy of people with Werner syndrome increases.

Screening and treatment for malignant tumors
Patients with Werner syndrome should be assessedfor presence of malignant tumors. Regular medical
checkups and cancer screening lead to early detection
and treatment. Patients should undergo blood andurine tests at least once every 3 months, and chest Xrays, thyroid ultrasound, abdominal ultrasound, fecal
occult blood tests, etc. every 6 months to 1 year. A
whole body assessment should be performed daily. In
particular, a doctor should be consulted if an
irregularly shaped “mole” develops on the skin or if a“swelling” under the skin increases in size.
The treatment for malignant tumors that develop in
Werner syndrome patients is the same as that in thegeneral population. Some patients express concern
about undergoing surgery because the wounds thatform on their hands and feet do not easily heal.
Wounds caused by surgery (e.g., lung cancer) on thecentral part of the body (trunk) easily heals, and thepatients undergo the same procedures that are usually
performed.

Characteristics of malignant mole melanoma

1. Irregular shape
4. Diameter≥6 mm
2. Jagged margin

3. Uneven color

5. Gradually grows larger
13

Ministry of Health, Labour and Welfare Research Grant
Intractable Disease Policy Research Project
Multidisciplinary research aimed at improving the medical standards and QOL for progeria
Koutaro Yokote, Endocrinology, Hematology, and Gerontology, Graduate School of
Medicine and School of Medicine, Chiba University
Minoru Takemoto, Department of Diabetes, Metabolism, and Endocrinology, Faculty of
Medicine, International University of Health and Welfare
Hironori Nakagami, Department of Health and Developmental Medicine, Graduate
School of Medicine, Osaka University
Yoshitaka Kubota, Department of Plastic and Reconstructive Surgery, Graduate
School of Medicine and School of Medicine, Chiba University
Rika Kosaki, Department of Medical Genetics, Department of Biodefense Internal
Medicine, National Center for Child Health and Development
Seiichiro Motegi, Department of Dermatology, Gunma University Graduate School of
MedicineToshibumi Taniguchi, Department of Infectious Diseases, Chiba
University Hospital
Kenji Ihara, Department of Pediatrics, Oita University School of
Medicine
Hideo Kaneko, Department of Pediatrics, Gifu Prefectural General
Medical Center
Masafumi Kuzuya, Department of Geriatrics, Nagoya University
Graduate School of Medicine
Akira Taniguchi, Department of Orthopedic Surgery, Nara Medical University
Muneaki Matsuo, Department of Pediatrics, Faculty of Medicine, Saga University
Toshiyuki Oshitari, Department of Ophthalmology, Graduate School of Medicine and School of Medicine,
Chiba University
Seijiro Mori, Department of Diabetes, Metabolism and Endocrinology, Tokyo Metropolitan Geriatrics
Medical Center
Kazuhisa Tsukamoto, Department of Internal Medicine, Teikyo University School of
Medicine
Yoshiro Maezawa, Endocrinology, Hematology, and Gerontology, Graduate School of
Medicine and School of Medicine, Chiba University
Masaya Koshizaka, Endocrinology, Hematology, and Gerontology, Graduate School of
Medicine and School of Medicine, Chiba University
Shunichiro Onishi, Department of Diabetes, Metabolism, and Endocrinology, Faculty of
Medicine, International University of Health and Welfare
Hisaya Kato, Endocrinology, Hematology, and Gerontology, Graduate School of Medicine
and School of Medicine, Chiba University
Naoko Tomoda, Endocrinology, Hematology, and Gerontology, Graduate School of
Medicine and School of Medicine, Chiba University
Cooperation：Werner Syndrome Patient/Family Group

March 2021