Bamforth–Lazarus syndrome

Overview

Bamforth–Lazarus syndrome is a rare congenital disorder characterized by the combination of congenital hypothyroidism, cleft palate, spiky hair, and choanal atresia (blockage of the nasal airway). It is also known as congenital hypothyroidism with cleft palate and choanal atresia. The syndrome was first described by Bamforth and Lazarus and is associated with mutations affecting thyroid gland development and other midline craniofacial structures. Although very rare, it is important to recognize due to its potentially life-threatening airway complications in neonates.

Causes

Bamforth–Lazarus syndrome is caused by mutations in theFOXE1 gene(also known as TTF-2, or thyroid transcription factor 2) located on chromosome 9. This gene plays a crucial role in the development of the thyroid gland, palate, and other midline facial structures. The condition is inherited in anautosomal recessive pattern, meaning a child must inherit two defective copies of the gene—one from each parent—to develop the syndrome. Key causes include:

• Mutations in FOXE1 gene involved in thyroid and craniofacial development

• Autosomal recessive inheritance, often with a family history of consanguinity

Symptoms

The clinical features of Bamforth–Lazarus syndrome are present from birth and include a combination of endocrine, craniofacial, and airway abnormalities:

• Congenital hypothyroidism – due to thyroid agenesis or dysgenesis

• Cleft palate – ranging from mild to complete cleft

• Choanal atresia – blocked nasal passages causing breathing difficulty in neonates

• Spiky or coarse hair – a unique dermatological finding

• Low nasal bridge and midface hypoplasia

• Developmental delay – if hypothyroidism is untreated or diagnosis is delayed

The combination of cleft palate and choanal atresia may lead to feeding and respiratory challenges early in life.

Diagnosis

Diagnosis is based on clinical findings, endocrine evaluation, and genetic testing:

• Neonatal thyroid screening showing elevated TSH and low T4 levels (indicative of hypothyroidism)

• Physical examination identifying cleft palate and abnormal hair texture

• Nasal endoscopy or imaging to confirm choanal atresia

• Genetic testing to detect FOXE1 gene mutations

• Family history assessment to identify autosomal recessive inheritance pattern

Treatment

Management of Bamforth–Lazarus syndrome is multidisciplinary, focusing on hormone replacement, surgical correction, and supportive care:

• Thyroid hormone replacement therapy (levothyroxine) – initiated as early as possible to prevent developmental delay

• Surgical repair of cleft palate – typically performed in infancy to improve feeding and speech

• Surgical correction of choanal atresia – especially if airway obstruction is severe

• Feeding support – including possible use of feeding tubes in newborns

• Regular developmental assessments and physical therapy if needed

Prognosis

The prognosis for individuals with Bamforth–Lazarus syndrome depends largely on the timing and effectiveness of thyroid hormone replacement and the management of structural anomalies:

• Excellent outcome if hypothyroidism is treated early and airway issues are resolved

• Normal intellectual development is possible with early hormone therapy

• Surgical outcomes for cleft palate and choanal atresia are generally favorable

• Long-term follow-up is essential for monitoring growth, development, and speech

With timely intervention, many children can achieve good physical and developmental outcomes.