Hypothyroidism, Thyroidal Or Athyroidal, With Spiky Hair And Cleft Palate

A number sign (#) is used with this entry because of evidence that Bamforth-Lazarus syndrome is caused by homozygous mutation in the FKHL15 gene (FOXE1; 602617) on chromosome 9q22.

Clinical Features

Bamforth et al. (1989) described 2 brothers with athyroidal hypothyroidism, spiky hair, choanal atresia, cleft palate, and bifid epiglottis. Polyhydramnios was present in the third trimester in both pregnancies. The parents were nonconsanguineous, and the mother and father were 23 and 27 years old, respectively, at the birth of their first child. Buntincx et al. (1993) reported a female child with the same syndrome. Choanal atresia may have been responsible for the polyhydramnios which was observed in all 3 cases. The unusual spiky or curly hair extended onto the forehead.

Clifton-Bligh et al. (1998) restudied the brothers reported by Bamforth et al. (1989). At the time of 1998 report, the boys were aged 16 and 13 years. They were receiving thyroxine replacement, with normal physical growth, pubertal development, and anterior pituitary function. In neither case was thyroid tissue detected by (123)I scanning or by ultrasonography of the neck. Maternal thyroid function was normal both basally and in response to TRH. Chatterjee (1998) stated that abnormal hair growth had persisted in the 2 sibs despite adequate thyroxine therapy. Presumably this indicates an intrinsic abnormality of hair follicle development.

Castanet et al. (2002) described 2 male sibs, born to consanguineous parents, with congenital hypothyroidism, athyreosis, and cleft palate. Unlike previous cases, these patients had an incomplete phenotype, lacking choanal atresia and bifid epiglottis.

Baris et al. (2006) reported a child, the daughter of consanguineous Turkish parents, with Bamforth-Lazarus syndrome who presented with congenital hypothyroidism, bilateral choanal atresia, cleft palate, and spiky hair but who was not athyreotic. Thyroid ultrasonography and computed tomography examination indicated thyroid tissue in a eutopic location, although biochemical measurements and radioisotope scanning showed that it was nonfunctional.

Molecular Genetics

Clifton-Bligh et al. (1998) demonstrated that thyroid agenesis, cleft palate, and choanal atresia in the 2 brothers reported by Bamforth et al. (1989) was caused by a homozygous missense mutation (A65V; 602617.0001) in the gene encoding thyroid transcription factor-2.

Castanet et al. (2002) described a mutation (S57N; 602617.0002) in the FOXE1 gene in 2 male sibs, born to consanguineous parents, with congenital hypothyroidism, athyreosis, and cleft palate.

In a girl, born of consanguineous Turkish parents, with Bamforth-Lazarus syndrome, Baris et al. (2006) identified homozygosity for a missense mutation affecting a highly conserved residue within the forkhead DNA-binding domain of FOXE1 (R102C; 602617.0003).

Nomenclature

Chatterjee (1998) suggested that the name of Lazarus, the senior author of the report by Bamforth et al. (1989), should be included with that of Bamforth, his resident, in the designation of the syndrome.