On this page
Congenital hypothyroidism (dyshormonogenesis)
This type of congenital hypothyroidism results from problems with how the thyroid gland makes hormones. Early detection through newborn screening and treatment are crucial to prevent developmental issues.
Available at Jeen Health
Clinical tests that include this
Overview
Congenital hypothyroidism (dyshormonogenesis) is a disorder where a baby's thyroid gland does not produce enough thyroid hormones from birth. These hormones are essential for normal growth and development, particularly of the brain [PMID:36577883]. While other forms of congenital hypothyroidism involve an absent or underdeveloped thyroid gland, dyshormonogenesis means the gland is present but has difficulty making the hormones correctly. This condition is typically identified through routine newborn screening programmes in the UK.
Symptoms & clinical features
Newborns with congenital hypothyroidism due to dyshormonogenesis often show no obvious symptoms at birth or in the first few weeks, which is why newborn screening is so important. If untreated, symptoms can develop over time. These may include poor feeding, constipation, prolonged jaundice, reduced activity, and a hoarse cry. Physical signs might involve a puffy face, an enlarged tongue, and cold or mottled skin. Untreated congenital hypothyroidism can lead to significant developmental delays and intellectual disability [PMID:33671217].
Video: Genetics 101
Affected organs
The primary organ affected is the thyroid gland, which is a small, butterfly-shaped gland located in the neck. Its main function is to produce thyroid hormones. When this process is disrupted, nearly all body systems can be affected because thyroid hormones are crucial for metabolism, growth, and development. In particular, the brain, skeletal system, and heart can be significantly impacted if the condition is not detected and treated early.
Risks & severity
The severity of congenital hypothyroidism (dyshormonogenesis) can vary widely, from mild cases requiring little medication to severe forms needing lifelong treatment. The exact prevalence of congenital hypothyroidism due to dyshormonogenesis is not well established, but overall congenital hypothyroidism affects approximately 1 in 2,000 to 4,000 newborns [PMID:33671217]. The most significant risk if the condition is left untreated is irreversible intellectual disability and developmental delays. Early diagnosis and consistent treatment, often with thyroid hormone replacement, typically lead to excellent outcomes and normal development.
Genetic causes
Congenital hypothyroidism (dyshormonogenesis) is caused by pathogenic variants in genes involved in the thyroid hormone synthesis pathway. These variants lead to errors in the biochemical processes required to produce thyroid hormones. Three key genes associated with this condition are DUOX2, TG, and TPO. The DUOX2 gene provides instructions for making an enzyme called dual oxidase 2, which helps produce hydrogen peroxide in the thyroid gland. Hydrogen peroxide is critical in the final steps of thyroid hormone manufacturing [PMID:22096024]. Pathogenic changes in DUOX2 can disrupt this process. The TG gene codes for thyroglobulin, a large protein that serves as a framework for thyroid hormone synthesis and storage. Variants in TG can impair this crucial scaffold. The TPO gene instructs the production of thyroid peroxidase, an enzyme essential for adding iodine to thyroglobulin and linking hormone precursors.
- DUOX2 dual oxidase 2The DUOX2 gene provides instructions for the dual oxidase 2 enzyme, which is essential for thyroid hormone synthesis and can be linked to congenital hypothyroidism.
- TG thyroglobulin
- TPO thyroid peroxidase
Inheritance pattern
This type of congenital hypothyroidism is inherited in an autosomal recessive pattern. This means that an individual must inherit two altered copies of the same gene - one from each parent - to develop the condition. Parents who each carry one altered copy of the gene are typically healthy and do not show symptoms themselves; they are known as carriers. When two carriers have a child, there is a 25% chance that their child will inherit two altered copies and develop the condition, a 50% chance the child will be a carrier like their parents, and a 25% chance the child will inherit two normal copies of the gene.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
Diagnosis & testing
Congenital hypothyroidism is primarily diagnosed through the NHS Newborn Blood Spot Screening Programme, generally performed within the first five days of a baby's life. This screening tests for elevated levels of thyroid stimulating hormone (TSH), which indicates the thyroid gland is not producing enough hormones. If the screening result is abnormal, further blood tests are conducted to confirm the diagnosis and determine the thyroid hormone levels. Imaging studies, such as a thyroid ultrasound or scintigraphy, may also be used to assess the structure and function of the thyroid gland. Genetic testing for genes like DUOX2, TG, and TPO can confirm the specific genetic cause, which can be important for family planning and understanding the inheritance pattern. Referrals for such testing would typically come from a paediatrician or endocrinologist.
Management & lifestyle
Management of congenital hypothyroidism (dyshormonogenesis) in the UK focuses on prompt thyroid hormone replacement therapy, usually with levothyroxine, administered orally. The dose is carefully adjusted based on regular blood tests to ensure normal thyroid hormone levels, particularly during the critical period of brain development. Lifelong treatment is typically required. Children with this condition will be regularly monitored by a paediatric endocrinologist and a multidisciplinary team. Early and consistent treatment generally leads to normal growth and cognitive development. Genetic counselling is often recommended for families to understand the inheritance pattern and risks for future pregnancies.
UK care pathway
In the UK, suspected cases of congenital hypothyroidism identified through newborn screening are managed through specialist paediatric endocrine services within the NHS. Following a diagnosis, individuals are referred to a paediatric endocrinology team. Access to genetic testing and genetic counselling is typically facilitated through Clinical Genetics services, often following a referral from the treating paediatrician, aligned with NHS Genomic Medicine Service pathways. Genetic causes for congenital hypothyroidism (dyshormonogenesis) are covered by specific R-codes for genomic testing, such as R241 Congenital hypothyroidism.
Frequently asked questions
What happens if a baby with congenital hypothyroidism isn't treated?
Without treatment, congenital hypothyroidism can lead to severe developmental delays, intellectual disability, and growth problems. Early detection and treatment prevent most of these serious complications.
How is congenital hypothyroidism diagnosed in babies?
It's usually diagnosed through the routine NHS Newborn Blood Spot Screening Programme, which checks for high levels of TSH. If the screen is positive, further blood tests confirm the diagnosis.
Will my child need to take medication for their whole life?
Most children with congenital hypothyroidism due to dyshormonogenesis will require lifelong daily thyroid hormone replacement therapy, typically with levothyroxine. Regular monitoring by specialists ensures the correct dosage.
If my first child has this condition, what is the risk for future children?
Since this is an autosomal recessive condition, if both parents are carriers of the same altered gene, there is a 1 in 4 (25%) chance with each pregnancy that a child will inherit two altered copies and develop the condition. Genetic counselling can provide specific risk assessments for your family.
Are there different types of congenital hypothyroidism?
Yes, two main types are thyroid dysgenesis (where the thyroid gland doesn't develop properly) and dyshormonogenesis (where the gland is present but can't produce hormones effectively). Both lead to insufficient thyroid hormones.