Related Experiment Video
Updated: Apr 8, 2026
Role of Diffusion MRI Tractography in Endoscopic Endonasal Skull Base Surgery
Published on: July 5, 2021
Squamosal Suture Craniosynostosis Due to Hyperthyroidism Caused by an Activating Thyrotropin Receptor Mutation
Reeti Chawla1, Tord D Alden2, Aigerim Bizhanova3
11 Division of Pediatric Endocrinology, Phoenix Children's Hospital , Phoenix, Arizona.
Insights
A rare de novo mutation in the thyrotropin receptor caused congenital hyperthyroidism and craniosynostosis in an infant. Prompt treatment improved neurodevelopment, highlighting the importance of early diagnosis for this rare condition.
Area of Science:
- Pediatric Endocrinology
- Genetics
- Developmental Biology
Background:
- Congenital hyperthyroidism, often linked to maternal autoimmune thyroid disease, can cause developmental issues and craniosynostosis in infants.
- Rarely, it stems from activating mutations in the thyrotropin (TSH) receptor.
Observation:
- A 6-month-old infant presented with severe thyrotoxicosis, developmental delays, and evaluation for squamosal suture synostosis.
- This presentation suggested a non-autoimmune cause for the hyperthyroidism.
Findings:
- Genetic analysis revealed a de novo germline mutation (1895C>T) in exon 10 of the TSH receptor, leading to constitutive activation (T32I).
- This mutation was identified as the cause of the infant's congenital hyperthyroidism.
Implications:
- The infant's thyrotoxicosis and craniosynostosis were successfully treated with antithyroid medication and surgical repair, resulting in neurodevelopmental improvement.
- This case underscores the importance of considering non-autoimmune hyperthyroidism and craniosynostosis in infants, as timely intervention can normalize neurodevelopment.
Background:
Congenital hyperthyroidism can be a cause of failure to thrive, hyperactivity, developmental delay, and craniosynostosis during infancy. Most commonly, the condition occurs in the setting of maternal autoimmune thyroid disease. Rarely, congenital hyperthyroidism can also occur secondary to activating mutations within the thyrotropin (TSH) receptor.
Patient Findings:
A Hispanic male infant presented at age 6 months with severe thyrotoxicosis. At the time of presentation he was being evaluated for squamosal suture synostosis and he was noted to have significant developmental delays.
Summary:
The patient's thyrotoxicosis was initially treated with antithyroid medication, and he subsequently underwent craniosynostosis repair leading to neurodevelopmental improvement. DNA from the patient and his parents was submitted for mutational analysis of exons 9 and 10 of the TSH receptor. He was found to carry a monoallelic transition 1895C>T in exon 10 that resulted in the substitution of threonine at position 632 by isoleucine (T32I). This mutation resulted in constitutive activation of the TSH receptor. Neither parent carried this mutation indicating that the child has acquired a de novo germline mutation.
Conclusions:
We report the first case of squamosal suture craniosynostosis in a patient with non-autoimmune hyperthyroidism. Squamosal suture craniosynotosis is rare, often has a subtle presentation, and should be considered in all patients with this condition because prompt treatment of hyperthyroidism and craniosynotosis repair can lead to normalization of neurodevelopment.
Related Concept Videos
01:22Sutures of the Skull
Sutures are immobile joints between adjacent bones of the skull. The narrow gap between the bones is filled with dense, fibrous connective tissue that unites the bones. The long sutures located between the skull bones are not straight but instead follow irregular, tightly twisting paths. These twisting lines tightly...
01:23The Thyroid Gland
The follicles have a central cavity lined by simple cuboidal to squamous epithelial cells called follicular cells. These cells produce the glycoprotein...
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The...
01:14Cranial Bones: Superior and Posterior View
The frontal bone is the single bone that forms the forehead. At its anterior midline, between the eyebrows, there is a slight depression called the glabella. The frontal bone also forms the supraorbital margin of the orbit. Near the middle of this margin is the supraorbital foramen, the opening that provides passage for a sensory nerve to the forehead. The frontal bone is thickened just above each supraorbital margin,...
01:27Cranial Bones: Lateral View
The temporal bone forms the lower lateral side of the skull. The temporal bone is subdivided into several regions. The flattened upper portion is the squamous portion of the temporal bone. Below this area and projecting anteriorly is the zygomatic process of the temporal bone, which forms the posterior portion of the zygomatic arch. Posteriorly is the mastoid portion of the temporal bone. Projecting...
01:18Functions of Thyroid Hormones
TH is indispensable for the normal development and maturation of the skeletal, muscular, and nervous systems during fetal and childhood growth. It facilitates bone mineral turnover and regulates protein synthesis in developing tissues, contributing significantly to overall growth and...