Genetics
Klinefelter’s syndrome, 47,XXY or XXY syndrome is a condition caused by a chromosome aneuploidy. Affected individuals have at least two X chromosomes and at least one Y chromosome. The extra X chromosome is retained because of a nondisjunction event during meiosis (sex cell division).

Incidence

The XXY chromosome arrangement is one of the most common genetic variations from the XY karyotype, occurring in about 1 in 500 live male births.

Symptoms/Characteristics

• In adults, possible characteristics vary widely and include little or no indicatinon of affectedness, a lanky, youthful build and facial appearance, or a rounded body type with some degree of gynecomastia (increased breast tissue).
• Mean I.Q. between 85-90

1. Affected males are almost always effectively sterile
2. Some degree of language learning impairment may be present
3. Hypogonadism, patients will often have a low serum testosterone level but high serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels.
4. Microorchidism (i.e. small testicles)
5. Increased risk of germ cell tumors, breast cancer, and osteoporosis

Clinical Management
Although genetic variation is irreversible, symptoms associated with Klinefelter syndrome can be altered or treated in a number of ways, including the use of testosterone treatment

add(14)(q32) or 14q+
Additional chromosome material of unknown origin attached to band 14q32 has been observed in ALL and lymphoma.  It is also a relatively frequent finding in B-cell CLL, prolymphocytic leukemia, hairy cell leukemia, Waldenstroms macroglobulinemia, multiple myeloma, plasma cell leukemia, ATL, mycosis fungoides and Sezary’s syndrome.

t(8:14)(q24;q32) and t(2;8)(p12;q24)
Translocations between chromosomes 8 and 14 and 2 and 8 are observed in Burkitt’s non-Hodgkins lymphomas and B-cell ALL-L3.  In general, the t(2;8) and t(8;14) neoplasms are aggressive and associated with poor patient prognosis.

t(14;18)(q32;q21)
The t(14;18) has been observed in a wide variety of lymphoid neoplasms, but most often in non-Hodgkin’s lymphomas specifically, the follicular, small cleaved-cell type.  There have been a few reports of the t(14;18) having been found in Hodgkin’s disease.  It is not unusual to observe other chromosome changes associated with the presence of the t(14;18).

Rearrangements of 1q
Rearrangements of the chromosome 1 long arm have been observed in a wide variety of neoplastic and preneoplastic disease, most frequently in acute lymphocytic leukemia and non-Hodgkin’s lymphoma.

Genetics
Maple Syrup Urine Disease (MSUD) is caused by a deficiency of the metabolic enzyme branched-chain α-keto acid dehydrogenase (BCKDH).  This deficiency leads to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products in the blood and urine.  Several forms of the disease include classic severe MSUD, intermediate MSUD, intermittent MSUD, thiamine-responsive MSUD and E3-Deficient MSUD with lactic acidosis.  MSUD is inherited in an  autosomal recessive manner.

Incidence

• Affects approximately 1 in 180,000 individuals
• There is a much higher incidence of MSUD in individuals of Amish and Mennonite descent

Symptoms/Characteristics

In infants, symptoms include:

• Sweet-smelling urine
• Poor feeding
• Vomiting
• Dehydration
• Lethargy
• Hypotonia
• Seizures
• Ketoacidosis
• Neurological decline

Clinical Management

• A diet with minimal levels of the amino acids leucine, isoleucine, and valine must be maintained in order to prevent neurological damage
• Specialized protein preparations containing substitutes and adjusted levels of the amino acids have been synthesized for use in individuals with MSUD

Genetics
Miller-Dieker syndrome is characterized by a developmental defect of the brain, caused by incomplete neuronal migration.  The disease arises from the deletion of both the LIS1 and 14-3-3 epsilon gene located on chromosome 17 at 17p13.3.  Miller-Dieker is inherited in an autosomal dominant manner.  An estimated 80% of these cases develop sporadically.

Incidence
Affects approximately 1 in 50,000 individuals

Symptoms/Characteristics

• Delayed growth and mental development
• Smooth brain surface (lissencephaly)
• Multiple abnormalities of the brain, heart, kidney and gastrointestinal tract.
• Feeding difficulties
• Seizures
• Death tends to occur in infancy and childhood
• Severe visual problems

Facial Features

• Small mouth with a wide upper lip
• High forehead
• Low set ears
• Microcephaly

Clinical Management
Treatment depends on the severity of the symptoms the child develops over time.  Medical therapies are available to treat epilepsy, as well as the complications affecting the kidneys, heart, and intestinal tract.  Patients may benefit from a feeding tube.  Special education programs at school are beneficial.  Children with severe malformations of the brain most likely will not respond well to treatment.