What are the other Names for this Condition? (Also known as/Synonyms)

• PHC Syndrome
• Premolar Aplasia, Hyperhidrosis, and Canities Premature

What is Book Syndrome? (Definition/Background Information)

• Book Syndrome is a very rare type of ectodermal dysplasia. Signs and symptoms include premolar aplasia (when the premolars fail to develop); excessive sweating (hyperhidrosis); and premature graying of the hair
• Other features that have been reported in only one person include a narrow palate (roof of the mouth); hypoplastic (underdeveloped) nails; eyebrow anomalies; a unilateral simian crease; and poorly formed dermatoglyphics (skin patterns on the hands and feet)
• Book syndrome is inherited in an autosomal dominant manner

(Source: Book Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Book Syndrome? (Age and Sex Distribution)

• Book Syndrome is an extremely rare congenital disorder. The presentation of symptoms may occur following the birth of the child, during early or late childhood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Book Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Book Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for this syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Book Syndrome? (Etiology)

Presently, Book Syndrome has only been reported in one, large Swedish family (25 cases in 4 generations) and in one other isolated case.

• In the Swedish family, the syndrome was inherited in an autosomal dominant manner
• In autosomal dominant inheritance, having a mutation in only one copy of the responsible gene is enough to cause signs and symptoms of the condition

(Source: Book Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Book Syndrome?

The signs and symptoms of Book Syndrome reported in the Swedish family included:

• Premolar aplasia (when the premolars fail to develop)
• Excessive sweating (hyperhidrosis)
• Early whitening of the hair

Early whitening of the hair was the most constant symptom, being found in every affected family member. The age of onset of this symptom ranged from age 6 to age 23. In some cases, there was whitening of hair on other parts of the body such as the armpits, genital hair, and eyebrows. Two-thirds of the affected people had an abnormality of the sweat glands.

In the isolated case, additional features that were reported include:

• A narrow palate (roof of the mouth)
• Hypoplastic (underdeveloped) nails
• Eyebrow anomalies
• A unilateral simian crease
• Poorly formed dermatoglyphics (skin patterns on the hands and feet)

Based on the frequency of symptoms of Book Syndrome observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Hyperhidrosis (palmoplantar)
• Hypodontia
• Premature graying of hair
• Small hand

Frequently present symptoms in 30-79% of the cases:

• Abnormality of the eyebrow 
• Bilateral single transverse palmar creases 
• Hypoplastic fingernail      
• Narrow palate

(Source: Book Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Book Syndrome Diagnosed?

Due to the rarity of Book Syndrome and scarcity of reports in the medical literature, specific information about diagnosing Book syndrome is presently unavailable.

• In general, ectodermal dysplasias are diagnosed by the presence of specific symptoms affecting the hair, nails, sweat glands, and/or teeth
• When a person has at least two types of abnormal ectodermal features (e.g., malformed teeth and extremely sparse hair), the person is typically identified as being affected by an ectodermal dysplasia
• Specific genetics tests to diagnose ectodermal dysplasia are available for only a limited number of ectodermal dysplasias
• Unfortunately, there currently is no genetic test for Book Syndrome because the gene responsible for the condition has not yet been identified
• People who are interested in learning more about a diagnosis of ectodermal dysplasia for themselves or family members should speak with their dermatologist and/or dentist
• These specialists can help determine whether a person has signs and/or symptoms of ectodermal dysplasia

(Source: Book Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Book Syndrome?

The complications of Book Syndrome may include:

• Emotional stress due to cosmetic concerns
• Dental abnormalities

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Book Syndrome Treated?

There is no cure for Book Syndrome, since it is reportedly a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Book Syndrome be Prevented?

Currently, Book Syndrome may not be preventable, since it is believed to be a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Book Syndrome? (Outcomes/Resolutions)

• The prognosis of Book Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Book Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/