Acute Promyelocytic Leukemia (APL:M3) Info

t(15;17)(q22;q21 or12)
This translocation is a remarkably specific marker for acute promyelocytic leukemia (ANLL-M3).  This strong association is further exemplified by the fact that occasionally this translocation develops as a secondary aberration during CML blast transformation, with patients exhibiting disease characteristics indistinguishable from APL. Apart from these exceptional CML blast crisis patients, t(15;17) has not been detected in any malignancies other than ANLL-M3.  t(15;17) APL patients usually exhibit disseminated intravascular coagulation (DIC) and hyper- or micro-granulated promyelocytes.

Angelman Syndrome Info

Angelman syndrome results from absence of a functional copy of the UBE3A gene inherited from the mother.

  • Microdeletion on maternal chromosome 15q11.2-q13
  • UPD (loss of maternal chromosome 15 due to a trisomy rescue event)
  • Abnormal methylation pattern (imprinting defect)
  • Mutation of the UBE3A gene on the maternal chromosome 15

Affects approximately 1 in 15,000 individuals


  • Infants with Angelman syndrome appear normal at birth, but often have feeding problems in the first few months
  • Noticeable developmental delays are seen by 6 to 12 months
  • Seizures usually commence between 2 and 3 years of age
  • Children may have an imbalance of eye muscles (strabismus), under-pigmented skin, hair, and eye color, and hyperactive lower limb deep tendon reflexes
  • Hyperactivity, microcephaly, sleep disorders, ataxia, movement disorders (hand-flapping ) and balance disorders that can cause severe functional deficits
  • Individuals with Angelman syndrome can have normal life spans and generally do not show developmental deterioration as they age

Facial Features

  • Individuals with Angelman syndrome are characterized by macrostomia (a large mouth), a large jaw and open-mouthed expression, and an inclination for protruding the tongue
  • In addition, they are often smiling and have frequent outbursts of laughter

Clinical Management

  • Medical therapy for seizures is often necessary
  • In order to reach their development potential, individuals with Angelman syndrome require physical and occupational therapies, communication therapy, and behavioral therapies

B-cell CLL Info

Trisomy of chromosome 12 is most frequently observed in B-cell chronic lymphocytic leukemia(CLL).  It has also been observed in other types of neoplasms.  As a single chromosome change, +12-CLL patients have been reported to have a relatively good prognosis, while +12-CLL patients with additional chromosome changes may suggest a relatively poor prognosis.

Bloom Syndrome Info

The gene responsible in this disorder, blm, was mapped to 15q26.1 and its product was found to encode aRecQ DNA helicase.  It is involved in DNA replication and repair.  Bloom syndrome is an autosomal recessive disorder.  The predominant mutation is referred to as “blmAsh”, a 6-bp deletion and 7-bp insertion at nucleotide position 2281.


  • Affects approximately 1 in 48,000 Ashkenazi Jewish individuals
  • It is estimated that 1 in 110 of those who are of Jewish ancestry are carriers


  • Small stature, immunodeficiency, chromosomal instability, and a predisposition to different types of cancer and infection
  • Photosensitivity and elevated dark red blotches on the skin
  • Intelligence is typically unaffected, although mild mental retardation has been reported in some cases
  • Mean age of death is 27 years of age and is usually related to cancer
  • Men with Bloom syndrome are sterile
  • Women have reduced fertility and shortened reproductive span

Facial Features

  • Bloom syndrome individuals are characterized with having a long, narrow face with a prominent nose (due to lack of subcutaneous fat)
  • Telangiectatic erythema of the face (broken spider veins and redness of the skin)
  • Cheilitis (swelling of the lips)
  • Relatively large protruding ears

Clinical Management
There is currently no treatment for the underlying cause of Bloom’s syndrome.  Preventative measures should be taken, such as increased surveillance for infection, cancer and decreased exposure to sunlight and X-rays.  Bone marrow transplant is a possibility.

DiGeorge/Velocardiofacial Syndrome (VCFS) 22q11.2 Deletion Syndrome Info

DiGeorge syndrome is caused by a deletion on chromosome 22.  Approximately 90% of patients with DiGeorge syndrome have a deletion at the 22q11.2 region.  A small number of cases of DGS have defects on other chromosomes, notably 10p13. DiGeorge syndrome is inherited in an autosomal dominant manner.


  • Affects approximately 1 in 3,000 to 1 in 4,000 individuals
  • Most of the 22q11.2 deletion cases are de novo, however in about 10% of families, the deletion is inherited and other family members are affected or at risk for passing this deletion to their children
  • There is an overall 0.025% risk of the 22q11 deletion syndrome in the general population


  • Conotruncal heart defects (Tetralogy of Fallot, interrupted aortic arch, ventricular septal defects, vascular rings)
  • Palatal abnormalities
  • Feeding difficulties
  • Immunodeficiency due to absence or malformation of thymus
  • Hypocalcemia due to absence of malformation of parathyroid glands
  • Craniofacial abnormalities (see below)
  • Hearing loss or abnormal ear exams
  • Genitourinary anomalies (absent or malformed kidney)
  • Mental retardation (typically borderline to mild)
  • IQs are generally in the 70 to 90 range
  • Psychiatric disorders in adults (e.g., schizophrenia, bipolar disorder)
  • Autism

Facial Features

  • Small ears with squared upper ear
  • Hooded eyelids
  • Unilateral facial weakness
  • Small mouth, chin, and side areas of the nose tip
  • Palatal abnormalities (Cleft lip and/or palate for example)

Clinical Management

  • It is important that the immune problems in infants are identified early so that special precautions may be implemented regarding immunization and blood transfusions
  • Most treatment is directed at alleviating symptoms, infections are treated aggressively with antibiotics
  • Patients may undergo cardiac surgery for their heart abnormalities
  • Hypoparathyroidism causing hypocalcemia is often transient, but may require lifelong vitamin D treatment
  • Thymus transplantation can be used to address absence of the thymus in complete DiGeorge syndrome