The genetics of CAH
Matthew Neil Bainbridge / Associate Director – Pediatric Genomics
Rady’s Children’s Hospital
About 1 in 10,000 to 18,000 children are born with congenital adrenal hyperplasia (CAH). The most common cause of CAH, accounting for ~95% of all cases, is 21-hydroxylase deficiency (21HD). In the body 21-hydroxylase is created by a gene called CYP21A2. When this gene stops working properly not enough 21-hydroxylase is created. In south Asia, there are 6 main mutations in the CYP21A2 gene that cause CAH. These mutations may either make the gene work less efficiently or stop the gene from being made by the body at all. These latter mutations are more likely to lead to the more severe, salt wasting, form of the disease.
21HD is an autosomal recessive disease (see figure below). This means that both girls and boys have 2 copies of the gene and get the disease at approximately the same frequency. It also means you need to have both copies of this gene functioning improperly to get the disease. When you have one functioning copy and one non-functioning copy you will not have the disease but will be a “carrier” for CAH/21HD. In order to have a child with CAH, both parents must be carriers of the disease and the child must have gotten a bad copy of the gene from each parent. Most parents do not know they are carriers of the disease until they have a sick child as they show no outward signs of disease. Every child born to parental carriers has a 25% chance of getting the disease. If you have a child with CAH your other children will have a 50% chance of being a carrier for CAH and will be at increased risk of their own children developing CAH. Risk of having a child with CAH/21HD is increased if there is a family history of the disease, especially in families where cousins or other related individuals marry. Parents of a child with CAH should consider genetic testing for their unaffected children and should undergo genetic counselling to understand the risks of having more children.
Congenital Adrenal Hyperplasia
Congenital Adrenal Hyperplasia is an autosomal recessive genetic disorder, which means that it affects males and females in equal numbers, and that it requires both parents to pass on a gene in order for it to manifest as a disease. For a child to be born with any form of CAH, both parents must carry a gene for the disorder.
Growth Hormone Deficiency
Growth hormone (GH) is a protein made by the pituitary gland and released into the blood in brief pulses. The major way that GH promotes growth is by increasing levels of the hormone, insulin-like growth factor-1 (IGF-1), and its carrier protein, IGF binding protein-3 (IGFBP-3), in the blood.
Optic Nerve Hypoplasia
A child with the Syndrome of Optic Nerve Hypoplasia, also known as Septo Optic Dysplasia or DeMorsiers Syndrome, has under-developed optic nerves. The optic nerves carry messages from the eye to the brain. ONH is the single leading cause of blindness in infants and toddlers.
Russell Silver Syndrome
Russell-Silver syndrome (or Silver-Russell syndrome) is a rare genetic disorder characterized by delayed growth in-utero (IUGR) that spares head growth (meaning the newborn has a head size that is large for his body) and ongoing postnatal growth failure.
Small for Gestational Age
SGA (small for gestational age) generally describes any infant whose birth weight and/or birth length was less than the 3rd percentile, adjusted for prematurity (gestational age). Between 3% and 10% of live births each year are diagnosed as SGA.
Turner’s Syndrome occurs in 1 in 2,500 live female births. Approximately 98% of pregnancies with Turner’s Syndrome abort spontaneously and approximately 10% of fetuses from pregnancies that have spontaneously aborted have Turner’s Syndrome.
Connect with us!
We have created a Facebook page called Omkar’s Journey with Congenital Adrenal Hyperplasia to chronicle all possible events and scenarios in the life of a child with CAH, with a view to let new parents know what to expect.
➤ Step 1: Search for the group page on Facebook.
➤ Step 2: Please request to join.
➤ Step 3: Send a message to the Admin or an email to
[email protected] and let us know why you are interested in joining this group.