Holt-Oram syndrome - Gene Mutation of limbs and heart

Affects 1 in 100,000 individuals.
Autosomal dominant inheritance

Most cases result from new mutations in the gene
Mutations in the TBX5 gene cause Holt-Oram syndrome. This gene provides instructions for making a protein that plays a role in the development of the heart and upper limbs before birth
In particular, this gene appears to be important for the process that divides the developing heart into four chambers (cardiac septation).


People with Holt-Oram syndrome have abnormally developed bones in their upper limbs. At least one abnormality in the bones of the wrist (carpal bones) is present in affected individuals. Often, these wrist bone abnormalities can be detected only by X-ray. Individuals with Holt-Oram syndrome may have additional bone abnormalities including a missing thumb, a long thumb that looks like a finger, partial or complete absence of bones in the forearm, an underdeveloped bone of the upper arm, and abnormalities of the collar bone or shoulder blades. These skeletal abnormalities may affect one or both of the upper limbs. 


About 75 percent of individuals with Holt-Oram syndrome have heart (cardiac) problems, which can be life-threatening. 
The most common problem is a defect in the muscular wall (septum) such as
Atrial septal defect
Ventricular septal defect
They also have cardiac conduction disease

Williams syndrome

 Children with syndrome have a distinctive, "elfin" facial appearance, along with a low nasal bridge, an unusually cheerful demeanor and ease with strangers; developmental delay coupled with strong language skills; and cardiovascular problems, such as supravalvular aortic stenosis and transient hypercalcaemia.


Williams syndrome is caused by the deletion of genetic material from the region q11.23 of chromosome 7.

Image Courtesy: http://geneticsf.labanca.net/

1 in every 20,000 live births. Williams syndrome is considered an autosomal dominant condition
The diagnosis is confirmed using one of two possible genetic tests: micro-array analysis or the fluorescent in situ hybridization (FISH) test. The FISH test examines chromosome #7 and probes for the existence of two copies of the elastin gene. Since 98-99% of individuals with Williams syndrome lack half of the 7q11.23 region of chromosome #7, where the elastin gene is located, the presence of only one copy of the gene is a strong sign of the disorder.  


The American Academy of Pediatrics recommends annual cardiology evaluations for individuals with Williams syndrome. Other recommended assessments include: opthalmologic evaluations, an examination for inguinal hernia, objective hearing assessment, blood pressure measurement, developmental and growth evaluation, orthopedic assessments on joints, muscle tone, and ongoing feeding and dietary assessments to manage constipation and urinary problems.


Support Group: http://www.williams-syndrome.org/what-is-williams-syndrome AND http://www.wsf.org/

What is CATCH-22?

22q11.2 deletion syndrome, which has several presentations including DiGeorge syndrome (DGS), DiGeorge anomaly and velo-cardio-facial syndrome, is a syndrome caused by the deletion of a small piece of chromosome 22. . 


It has a prevalence estimated at 1:4000. The syndrome was described in 1968 by the pediatric endocrinologist Angelo DiGeorge.


Salient features can be summarized using the mnemonic CATCH-22 

Cardiac Abnormality (especially tetralogy of Fallot)
Abnormal facies
Thymic aplasia
Cleft palate
Hypocalcemia/Hypoparathyroidism. 
22 to remind one the chromosomal abnormality is found on the 22 chromosome


DiGeorge syndrome is caused by a large deletion from chromosome 22, produced by an error in recombination at meiosis (the process that creates germ cells and ensures genetic variation in the offspring). This deletion means that several genes from this region are not present in DiGeorge syndrome patients. It appears that the variation in the symptoms of the disease is related to the amount of genetic material lost in the chromosomal deletion. 

There is no cure for 22q11.2 deletion syndrome.The key is to identify each of the associated features and manage each using the best available treatments.

For example, in children it is important that the immune problems are identified early as special precautions are required regarding blood transfusion and immunisation with live vaccines. 

Thymus transplantation can be used to address absence of the thymus in the rare, so-called "complete" DiGeorge syndrome.

 Bacterial infections are treated with antibiotics. 

Cardiac surgery is often required for congenital heart abnormalities. 

Hypoparathyroidism causing hypocalcaemia often requires lifelong vitamin D and calcium supplements.

22q11.2 deletion syndrome is inherited in an autosomal dominant pattern. However, most cases are NOT inherited