Bamforth–Lazarus syndrome

Bamforth–Lazarus syndrome is a genetic condition that results in thyroid dysgenesis.^[1][2] It is due to recessive mutations in forkhead/winged-helix domain transcription factor (FKLH15 or TTF2).^[3] It is associated with FOXE1.^[4]

Bamforth–Lazarus syndrome
Other names	Athyroidal hypothyroidism-spiky hair-cleft palate syndrome

Genetics

Genetic inheritance

Bamforth–Lazarus syndrome is inherited in an autosomal recessive pattern, meaning that an affected individual inherits a pathogenic variant of the gene from each parent, who is typically an unaffected genetic carrier^[5]. Any child of two heterozygous parents who carry a pathogenic variant implicated in Bamforth–Lazarus syndrome has a 25 percent of being affected by the condition. Affected individuals have been commonly reported to have consanguinity in their family history^[6].

Pathogenic variants

Eight different pathogenic variants in the FOXE1 gene have been found in patients with Bamforth–Lazarus syndrome^[5]. Of the eight variants, six are missense mutations and two are frameshift mutations. Notably, as of 2025, one patient was identified to have inherited different FOXE1 variants from each parent, exhibiting one frameshift mutation and one missense mutation on their different copies of the gene^[5]. In all other reported cases of the disorder, affected patients had inherited two copies of the same pathogenic variant from their parents. These pathogenic variants have been shown to have either loss-of-function or gain-of-function effects on the FOXE1 gene, causing the activity of its forkhead DNA-binding domain to be either irregularly suppressed or enhanced^[6].