Extremely rare congenital genetic disorder combining
cleft palate and hypothyroidism.
Bamforth Syndrome; Congenital Hypothyroidism, Spiky Hair,
and Cleft Palate Syndrome.
Only five children
have been described. Autosomal recessive inheritance. The genetic defect affects the gene encoding thyroid
transcription factor-2, which is, among other factors such as thyroid
transcription factor-1, thyroid-stimulating hormone receptor genes, and
Pax-8, implicated in the early thyroid organogenesis. The hair defect seems to be
caused by a mutation in the FOXE 1 gene. Gene map locus is
Three children, two siblings and one single
child, showed neonatal respiratory distress, presumably from upper airway
obstruction. Facial features included choanal atresia, cleft palate, bifid
epiglottis, and micrognathia. Congenital hypothyroidism and spiky hair were
present at birth. Mild developmental delay was described in two and might
have been related to hypothyroidism. Thyroid agenesis is possible. Other features included polyhydramnios
in three cases and low-set ears.
Direct laryngoscopy and tracheal
intubation may be difficult because of micrognathia and malformations of the
palate and epiglottis. However, at least one child was mechanically
ventilated, and no difficulties with intubation were reported. Choanal
atresia precludes nasal intubation and respiratory distress can be marked in
the neonatal period and require surgical treatment. Two children had
recurrent aspirations and poor feeding, possibly because of pharyngeal
dysmotility. Chronic lung disease may be present secondary to chronic
aspirations and mechanical ventilation. These patients are on thyroid hormone
replacement therapy. Despite adequate therapy, these patients are usually of short stature.
Bamforth JS, Hughes IA, Lazarus JH, et al: Congenital hypothyroidism,
spiky hair, and cleft palate. J Med Genet
Brancaccio A, Minichiello A, Grachtchouk M, et al. Requirement of the forkhead gene
FOXE 1, a target of sonic hedgehog signaling, in hair follicle morphogenesis.
Hum Mol Genet 13;2595, 2004.
Buntinex IM, Van Overmeire B, Desager K, et al: Syndromic association of
cleft palate, bilateral choanal atresia, curly hair, and congenital
hypothyroidism. J Med Genet 30:427, 1993.