Rare Congenital Diseases

Rare congenital diseases are those which are present at birth. They may be diagnosed prenatally (before birth), at birth, or later in childhood. Congenital rare diseases are always present at birth but may not be diagnosed until afterwards, sometimes as late as adulthood. 

A rare disease is one, which in the US, affects less than 200,000 people nationally. This means its prevalence is generally low and it is not common. 

Congenital rare diseases may present with a wide range of varying symptoms. Some of these may be identified by ultrasound or genetic screening during pregnancy. Some of these symptoms may be obvious at birth, as birth defects, others may take longer to be noticeable. 

Just because a syndrome is present at birth does not necessarily make it easy or easier to diagnose than one which develops later in life. 


The accurate diagnosis of a rare disease, including a congenital one, rests on a number of factors including,

-The cause of the syndrome, if these causes are known, and if genetic testing can identify them

-The severity of symptoms, mild or progressive symptoms may not be noticed at birth, and if specific symptoms are understood within the context of a rare disease

-If a patient or family has access to a genetic counselor and genetic experts who can help place their symptoms and family medical history within the context of a rare disease

Rare congenital diseases – examples

22q11.2 deletion syndrome (Di George)

This rare congenital disease presents with a wide variety of symptoms that may vary in terms of their severity across affected individuals. This can make it more difficult to diagnose, especially at birth. 

Deletions on chromosome 22 cause the syndrome. There are a number of specific genes related to this deletion which are still being confirmed as the exact cause of the syndrome. 

The prevalence of this rare congenital disease is currently believed to be around 1 in every 4,000 live births in the US. Each case is usually the first in a family. 

CHARGE syndrome 

This rare congenital disease is difficult to diagnose even though it presents with several different birth defects. This is due to the fact that symptoms can vary widely between individuals in terms of their types and severity of presentation. Generally however symptoms of this syndrome affect the nervous system, and the eyes, nose and ears. 

This congenital disease is the result of mutations which occur in the CHD7 gene. Research is also ongoing into the SEMA3E gene as another possible cause. Because of the way in which this condition is inherited, parents who are carriers of the gene mutation responsible for the syndrome have a 50% chance of passing the syndrome on to their child. Only one parent needs to be a carrier of the mutation for a child to be affected by this condition. 

Smith-Lemli-Opitz syndrome

This congenital rare disease presents with slow physical growth that is often first identified intrauterine before a baby is born. It’s precise prevalence is around 1 in 20-60,000 live births. This rare disease has multiple symptoms, all of them present at birth, hence it is also often known as a multiple-congenital anomaly disorder. One of the main signs of the syndrome is intellectual disability. 

Generally this rare congenital disease is more common in Caucasians of specifically Central European descent. It is extremely rare in those of African and Asian ancestry. 

The specific gene responsible for this syndrome is the DHCR7 gene. The mutation on the gene leads to a deficiency of enzyme 7 dehydrocholesterol reductase. This in turn produces low cholesterol levels and triggers some of the symptoms of the rare disease. 

In order to inherit the disease, an individual must receive two copies of the specific gene mutation from both parents. Children born to parents who are both carriers for this specific gene change, have a 25% chance of being born with this congenital rare disease.


There is still much that needs to be done to raise general rare disease awareness about congenital syndromes, including their causes and symptoms. The more we know about each syndrome, the greater diagnosis and testing becomes. 



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