Bloom syndrome

# Overview
Bloom syndrome is a rare inherited disorder characterized by a high frequency of breaks and rearrangements in an affected person's chromosomes .

# Historical Perspective
Bloom syndrome was discovered and first described by dermatologist Dr. David Bloom in 1954

# Pathophysiology

## Genetics
Mutations in the BLM gene (locus 15q26.1) cause Bloom syndrome.  The BLM gene provides instructions for producing a protein called the Bloom (BLM) syndrome protein, which is a member of the DNA helicase family.  DNA helicases are enzymes that unwind the two spiral strands of a DNA molecule so that they can be copied.  When a cell prepares to divide to form two cells, the chromosomes are duplicated so that each new cell will get a complete set of chromosomes; this replication process involves unwinding the DNA so that it can be copied.
The BLM protein is important in maintaining the stability of the DNA during this process.  Mutations in the BLM gene alter or reduce the BLM protein's DNA helicase activity, which causes errors in the copying process during replication.  As a result, people with Bloom syndrome have a higher frequency of chromosome breakage and rearrangement than unaffected people.  This increase in chromosome breakage and rearrangement leads to the signs and symptoms of Bloom syndrome.  Another suggestion put forward is that persons with Bloom syndrome overproduce the superoxide anion, whose volatility damages the affected person's chromosomes.
Bloom syndrome is inherited in an autosomal recessive fashion.  Both parents must be carriers in order for a child to be affected.  The carrier frequency in individuals of Eastern European ancestry is about 1/100.  If both parents are carriers, there is a one in four, or 25%, chance with each pregnancy for an affected child.  Genetic counseling and genetic testing is recommended for families who may be carriers of Bloom syndrome.

# Epidemiology and Demographics
- Bloom syndrome is a very rare disorder in most populations, and its overall frequency is unknown.
- The disorder is more common in people of Central and Eastern European (Ashkenazi) Jewish background, among whom about 2 in 100,000 are affected. Approximately one-third of people with Bloom syndrome are of Ashkenazi Jewish descent.

# Natural History, Complications and Prognosis
- Chromosomal instability in Bloom syndrome results in a high risk of cancer in affected individuals. Affected individuals develop the full range of cancers found in the general population, but the cancers arise unusually early in life. People with Bloom syndrome may be first diagnosed with cancer at about 25 years old.
- Patients with Bloom syndrome are also higher risk for immune deficiency.
- Chronic lung problems - bronchiectasis
- Diabetes
- Intrauterine death
- Intrauterine growth retardation

# Diagnosis

## Symptoms
Common symptoms experienced by patients with Bloom syndrome include:
- Infertility in men - they do not produce sperm, and as a result are unable to father children (infertile).
- Early menopause in women - earlier than usual
- Recurrent infections - e.g pneumonia, ear infections due to immune suppression.
- Learning disabilities and mental retardation
- Photo sensitivity of the skin.

# Physical Examination

## Appearance of the patient
- People with Bloom syndrome are much smaller than average (short stature), and often have a high-pitched voice.
- Their adult height is less than 5 feet.

## Skin
- They tend to develop pigmentation changes and dilated blood vessels in the skin, particularly in response to sun exposure. These changes often appear as a butterfly-shaped patch of reddened skin on the face. The skin changes may also affect the hands and arms.

### Gallery
- url = >
- url = >
- url = >
- url = >
- url = >

## Head
- Long, narrow face / Dolichocephaly
- Small lower jaw

## Ear
- Prominent ears

## Nose
- Prominent nose

### Extremities
- Clinodactyly
- Polydactyly
- Syndactyly

### Neurologic
- Mental retardation

## Laboratory Findings
- Hypogammaglobulinaemia