National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Bamforth syndrome



Other Names:
Hypothyroidism cleft palate Hypothyroidism, athyroidal, with spiky hair and cleft palate; Bamforth-Lazarus syndrome
Categories:

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 1226

Definition
A very rare syndrome of congenital hypothyroidism characterized by thyroid dysgenesis (in most cases athyreosis), cleft palate and spiky hair, with or without choanal atresia, and bifid epiglottis. Facial dysmorphism and porencephaly have been reported in isolated cases.

Epidemiology
Only 8 patients from 6 families have been reported to date.

Clinical description
The syndrome is typically observed at birth with cleft palate, spiky hair and thyroid dysgenesis (in most cases athyreosis) leading to congenital hypothyroidism that manifests with lethargy, poor feeding, macroglossia, cold or mottled skin, persistent jaundice, and umbilical hernia. Neonatal hyperbilirubinemia is also common. Some may also present with choanal atresia and bifid epiglottis. Facial dysmorphism, consisting of microcephaly, hypertelorism, anteverted nares, narrow nasal bridge, low-set ears, small jaw and retrognathia, has been reported in one case. Porencephaly was also recently described in one case.

Etiology
Bamforth-Lazarus syndrome is due to homozygous loss-of-function missense mutations located within the forkhead domain of the FOXE1 gene (9q22), encoding thyroid transcription factor 2 (TTF-2). TTF-2 is expressed in the thyroid gland (as well as elsewhere like the tongue, epiglottis and palate) and is thought to play a crucial role in thyroid morphogenesis. Cases reported so far have all been due to homozygous loss-of-function mutations apart from one case described with a novel FOXE1 homozygous mutation causing increased thyroid gene expression.

Diagnostic methods
Diagnosis is based on clinical findings of congenital hypothyroidism with cleft palate and spiky hair along with findings of thyroid ultrasonography (USG) and computed tomography examination. Thyroid tissue is either completely absent or non-functional. Serum thyroid stimulation hormone (TSH) levels should be measured (levels will be elevated on newborn screening filter paper test, as is seen in all cases of athyreosis) to determine necessary treatment dosage. Molecular genetic testing can identify a mutation in the FOXE1 gene, confirming diagnosis.

Differential diagnosis
Differential diagnoses include other forms of syndromic hypothyroidism such as Johanson-Blizzard syndrome.

Antenatal diagnosis
Whilst prenatal diagnosis is not performed, a cleft palate and, in some cases, polyhydramnios (resulting from choanal atresia) may be observed during routine antenatal sonography.

Genetic counseling
The disease is inherited autosomal recessively and genetic counseling is possible. Most of the patients reported to date came from consanguineous parents, both being heterozygous for the genetic mutation. Where both parents are heterozygous carriers, there is 25% risk of transmitting the disease to offspring.

Management and treatment
Thyroid hormone replacement therapy is the standard treatment for those with Bamforth-Lazarus syndrome and should be started as soon as possible. The dosage of synthetic thyroxine (T4) necessary depends on the patient's age, weight and any other medical conditions. Regular follow up is recommended to monitor any fluctuation in TSH levels and treatment is lifelong. In neonates born with hyperbilirubinemia, phototherapy is often effective. Surgical procedures for cleft palate (maxillo-facial reconstruction and plastic surgery) and choanal atresia (surgery to reopen the nasal passages) should be discussed in a specialized health center. Speech therapy may also be required.

Prognosis
With proper treatment adherence the prognosis is good and children can have normal physical growth, pubertal development, and anterior pituitary function. Quality of life, however, can be affected by cleft palate/choanal atresia as multiple surgeries may be necessary. Intellectual development is normal if treatment for hypothyroidism is not delayed.

Visit the Orphanet disease page for more resources.
Last updated: 6/1/2019

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 10 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal hair quantity 0011362
Choanal atresia
Blockage of the rear opening of the nasal cavity
Obstruction of the rear opening of the nasal cavity
[ more ]
0000453
Cleft palate
Cleft roof of mouth
0000175
Congenital hypothyroidism
Underactive thyroid gland from birth
0000851
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ]
0001249
Polyhydramnios
High levels of amniotic fluid
0001561
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw
[ more ]
0000278
Thyroid agenesis 0008191
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Bifid epiglottis 0010564
Showing of 10 |
Last updated: 7/1/2020

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources


These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Bamforth syndrome. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.