MCID: BMF002
MIFTS: 18

Bamforth Syndrome

Categories: Endocrine diseases, Rare diseases

Aliases & Classifications for Bamforth Syndrome

MalaCards integrated aliases for Bamforth Syndrome:

Name: Bamforth Syndrome 52 29 6 71
Hypothyroidism Cleft Palate Hypothyroidism, Athyroidal, with Spiky Hair and Cleft Palate 52
Bamforth-Lazarus Syndrome 52

Classifications:



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UMLS 71 C1855794

Summaries for Bamforth Syndrome

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. 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.

MalaCards based summary : Bamforth Syndrome, also known as hypothyroidism cleft palate hypothyroidism, athyroidal, with spiky hair and cleft palate, is related to hypothyroidism, thyroidal or athyroidal, with spiky hair and cleft palate and hypothyroidism, congenital, nongoitrous, 2. An important gene associated with Bamforth Syndrome is FOXE1 (Forkhead Box E1). Affiliated tissues include thyroid, skin and testes.

Related Diseases for Bamforth Syndrome

Graphical network of the top 20 diseases related to Bamforth Syndrome:



Diseases related to Bamforth Syndrome

Symptoms & Phenotypes for Bamforth Syndrome

Drugs & Therapeutics for Bamforth Syndrome

Search Clinical Trials , NIH Clinical Center for Bamforth Syndrome

Genetic Tests for Bamforth Syndrome

Genetic tests related to Bamforth Syndrome:

# Genetic test Affiliating Genes
1 Bamforth Syndrome 29 FOXE1

Anatomical Context for Bamforth Syndrome

MalaCards organs/tissues related to Bamforth Syndrome:

40
Thyroid, Skin, Testes, Tongue, Pituitary, Breast

Publications for Bamforth Syndrome

Articles related to Bamforth Syndrome:

# Title Authors PMID Year
1
Bamforth syndrome: is porencephaly a new finding? 61
24341142 2013
2
Overexpression of mouse TTF-2 gene causes cleft palate. 61
22304410 2012
3
Spectrum of Human Foxe1/TTF2 Mutations. 61
20453517 2010
4
Unexpected prolonged paralysis after mivacurium in a patient with Bamforth syndrome. 61
16884476 2006
5
Distribution of the titf2/foxe1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair. 61
12203737 2002
6
An autosomal recessive syndrome of choanal atresia, hypothelia/athelia and thyroid gland anomalies overlapping bamforth syndrome, ANOTHER syndrome and methimazole embryopathy. 61
12002153 2002

Variations for Bamforth Syndrome

ClinVar genetic disease variations for Bamforth Syndrome:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FOXE1 NM_004473.4(FOXE1):c.194C>T (p.Ala65Val)SNV Pathogenic 6986 rs104894110 9:100616390-100616390 9:97854108-97854108
2 FOXE1 NM_004473.4(FOXE1):c.170G>A (p.Ser57Asn)SNV Pathogenic 6987 rs28937575 9:100616366-100616366 9:97854084-97854084
3 FOXE1 NM_004473.4(FOXE1):c.743C>G (p.Ala248Gly)SNV Uncertain significance 208453 rs538912281 9:100616939-100616939 9:97854657-97854657
4 FOXE1 NM_004473.4(FOXE1):c.505_507GCC[7] (p.Ala176_Ala179del)short repeat Likely benign 522197 rs71369530 9:100616701-100616712 9:97854419-97854430
5 FOXE1 NM_004473.4(FOXE1):c.285A>G (p.Lys95=)SNV Benign/Likely benign 435238 rs139551528 9:100616481-100616481 9:97854199-97854199
6 FOXE1 NM_004473.4(FOXE1):c.512_513insTGCCGCAGC (p.Ala177_Ala179dup)insertion Benign 522287 rs755194188 9:100616706-100616707 9:97854424-97854425
7 FOXE1 NM_004473.4(FOXE1):c.387T>C (p.Leu129=)SNV Benign 95096 rs3021523 9:100616583-100616583 9:97854301-97854301
8 FOXE1 NM_004473.4(FOXE1):c.505_507GCC[9] (p.Ala178_Ala179del)short repeat Benign 95097 rs71369530 9:100616701-100616706 9:97854419-97854424
9 FOXE1 NM_004473.4(FOXE1):c.825C>T (p.Ser275=)SNV Benign 95098 rs3021526 9:100617021-100617021 9:97854739-97854739

Expression for Bamforth Syndrome

Search GEO for disease gene expression data for Bamforth Syndrome.

Pathways for Bamforth Syndrome

GO Terms for Bamforth Syndrome

Sources for Bamforth Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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