Alternative titles; symbols
SNOMEDCT: 722375007; ORPHA: 1226; DO: 0050655;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 9q22.33 | Bamforth-Lazarus syndrome | 241850 | Autosomal recessive | 3 | FOXE1 | 602617 |
A number sign (#) is used with this entry because of evidence that Bamforth-Lazarus syndrome (BAMLAZ) is caused by homozygous mutation in the FKHL15 gene (FOXE1; 602617) on chromosome 9q22.
Bamforth-Lazarus syndrome (BAMLAZ) is a rare autosomal recessive disorder characterized by congenital hypothyroidism due to thyroid agenesis or thyroid hypoplasia, cleft palate, and spiky hair, with or without choanal atresia or bifid epiglottis (summary by Sarma et al., 2022).
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.
Sarma et al. (2022) reported an 18-year-old patient who was diagnosed with cleft palate soon after birth and with congenital hypothyroidism at 2 months of age. He had developmental delay and impaired intellectual development. At 6 years of age he had sparse and spiky hair, a large head, and a triangular face. He also had cafe-au-lait macules on his trunk. By 18 years of age, he progressed into puberty. He had sparse hair that was increased in density since childhood and no longer spiky. He had bilateral mixed hearing loss. Imaging studies demonstrated absence of thyroid tissue. A cardiac evaluation showed mild dilation of the right atrium, tricuspid regurgitation, and pulmonary arterial hypertension.
The transmission pattern of BAMLAZ in the family reported by Castanet et al. (2002) was consistent with autosomal recessive inheritance.
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 FKHL15 gene.
Castanet et al. (2002) identified 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).
In an 18-year-old man, born of consanguineous parents, with BAMLAZ, Sarma et al. (2022) identified a homozygous 1-bp duplication (c.141dupC; 602617.0005) in the FOXE1 gene. The mutation, which was identified by whole-exome sequencing and confirmed by Sanger sequencing, was present in heterozygous state in his parents and his unaffected sib.
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.
Bamforth, J. S., Hughes, I. A., Lazarus, J. H., Weaver, C. M., Harper, P. S. Congenital hypothyroidism, spiky hair, and cleft palate. J. Med. Genet. 26: 49-60, 1989. [PubMed: 2918525] [Full Text: https://doi.org/10.1136/jmg.26.1.49]
Baris, I., Arisoy, A. E., Smith, A., Agostini, M., Mitchell, C. S., Park, S. M., Halefoglu, A. M., Zengin, E., Chatterjee, V. K., Battaloglu, E. A novel missense mutation in human TTF-2 (FKHL15) gene associated with congenital hypothyroidism but not athyreosis. J. Clin. Endocr. Metab. 91: 4183-4187, 2006. [PubMed: 16882747] [Full Text: https://doi.org/10.1210/jc.2006-0405]
Buntincx, I. M., Van Overmeire, B., Desager, K., Van Hauwaert, J. Syndromic association of cleft palate, bilateral choanal atresia, curly hair, and congenital hypothyroidism. J. Med. Genet. 30: 427-428, 1993. [PubMed: 8320710] [Full Text: https://doi.org/10.1136/jmg.30.5.427]
Castanet, M., Park, S.-M., Smith, A., Bost, M., Leger, J., Lyonnet, S., Pelet, A., Czernichow, P., Chatterjee, K., Polak, M. A novel loss-of-function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate. Hum. Molec. Genet. 11: 2051-2059, 2002. [PubMed: 12165566] [Full Text: https://doi.org/10.1093/hmg/11.17.2051]
Chatterjee, V. K. Personal Communication. Cambridge, England 8/19/1998.
Clifton-Bligh, R. J., Wentworth, J. M., Heinz, P., Crisp, M. S., John, R., Lazarus, J. H., Ludgate, M., Chatterjee, V. K. Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia. Nature Genet. 19: 399-401, 1998. [PubMed: 9697705] [Full Text: https://doi.org/10.1038/1294]
Sarma, A. S., Banda, L., Rao Vupputuri, M., Desai, A., Dalal, A. A new FOXE1 homozygous frameshift variant expands the genotypic and phenotypic spectrum of Bamforth-Lazarus syndrome. Europ. J. Med. Genet. 65: 104591, 2022. [PubMed: 35963604] [Full Text: https://doi.org/10.1016/j.ejmg.2022.104591]