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Form of acrocephalosyndactyly characterized by variable craniosynostosis, dysmorphic facies, and minimal syndactyly of hands and feet.
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First reported in 1931 by the Norwegian psychiatrist Haakon Sæthre (1891–1945), followed in 1932 by the German psychiatrist Fritz Chotzen (1871–1937).
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Approximately 3 in 100,000 live births.
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Autosomal dominant with a high penetrance and variability in expressivity. Mutations in the TWIST1 gene, which has been mapped to chromosome 7p21-p22, are responsible for Saethre-Chotzen Syndrome.
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The TWIST1 (Twist Family Basic Helix-Loop-Helix Transcription Factor 1) gene regulates the synthesis of a transcription factor protein that belongs to a large protein family known as basic helix-loop-helix (bHLH) transcription factors and controls the activity of particular genes. The bHLH domain determines the protein’s spatial appearance and allows it to target specific DNA sequences thereby enabling them to help regulate fetal tissue and organ development, particularly mesenchymal tissues (bones, muscles) of the head and distal limbs. TWIST1 is also involved in the regulation of fibroblast growth factor receptor 2 (FGFR-2). The gene mutations lead to an increased maturation rate of the osteoblastic cell lineage. This leads to increased subperiosteal bone formation and premature ossification in the calvarium during fetal development and forms the basis for craniosynostosis.
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Based on the clinical findings at birth. Skull radiographs will confirm the craniofacial osseous abnormalities and premature coronal craniosynostosis.
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There is a wide phenotype with regards to the severity of this disorder. The degree of craniosynostosis can be profound, but may also be very mild (so that the diagnosis is missed for a prolonged period of time) and is often asymmetrical. The coronal sutures are most commonly involved resulting in brachycephaly (or plagiocephaly if only one suture is affected). However, involvement of the metopic (resulting in trigonocephaly) or the lambdoid suture (resulting in occipital flattening) has also been described. Despite the fact that craniosynostosis leads to some degree of increased intracranial pressure (ICP) in these patients, most show normal mental development. The face is typically flat and often asymmetrical with a wide forehead, low frontal hairline, ptosis, hypertelorism, hypoplastic maxilla, deviated nasal septum, high-arched palate (or rarely cleft palate), and dental anomalies (eg, abnormal enamel with cavities). The ears are often small and low-set with prominent crura and hearing impairment may occur. Syndactyly is of variable extent, but typically mild and most commonly involves fingers II and III, (usually cutaneous syndactyly, but separate bone structures). The thumbs are most often normal (or show slight flattening), while brachy- and clinodactyly of the fifth finger are quite variable. Cutaneous syndactyly of toes II and III (typically) and broad halluces with valgus deformity (and occasionally notched or bifid terminal ...