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TTF1-associated pneumopathy

Thursday 29 April 2010

Thyroid transcription factor-1 (TTF-1) deficiency syndrome is characterized by neurologic, thyroidal and pulmonary dysfunction.

Children usually have mild-to-severe respiratory symptoms and occasionally die of respiratory failure.

Synopsis

- respiratory insufficiency
- mild hyaline membrane disease
- continuous ventilatory support
- symmetrically distributed pulmonary cysts by imaging.
- pneumonia
- respiratory failure

Pathology

- visible emphysematous changes
- "cysts" up to 2 mm in diameter.
- The airway generations and radial alveolar count were diminished.
- Acute bacterial pneumonia, alveolar septal fibrosis, pneumocyte hypertrophy and clusters of airspace macrophages can be focally present.
- Abnormal airway and alveolar morphogenesis
- Altered expression of surfactant-associated proteins, which may explain the respiratory difficulties encountered in TTF-1 haploinsufficiency.

Physiopathology

- TTF-1 plays an important role in pulmonary morphogenesis and surfactant metabolism.

Ultrastructure

- Type II pneumocytes have numerous lamellar bodies.
- Alveolar spaces contain fragments of type II pneumocytes and extruded lamellar bodies.

Immunochemistry

- Immunoreactivity for surfactant protein SP-A and ABCA3 is diminished.
- Immunoreactivity for SP-B and proSP-C is robust, although irregularly distributed, corresponding to the distribution of type II pneumocytes.
- Immunoreactivity for TTF-1 protein is readily detected.

Etiology

- constitutional 14q12-21.3 haploid deletion encompassing the TTF-1

  • cerebral dysgenesis
  • thyroidal dysfunction

References

- A novel presentation of diffuse lung disease caused by congenital hypothyroidism. Shenoy A, Esquibies AE, Dunbar N, Dishop MK, Reyes-Mugica M, Langston C, Deladoëy J, Abu-Khudir R, Carpenter T, Bazzy-Asaad A. J Pediatr. 2009 Oct;155(4):593-5. PMID: 19773006

- Pulmonary Pathology in Thyroid Transcription Factor-1 Deficiency Syndrome. Galambos C, Levy H, Cannon CL, Vargas SO, Reid LM, Cleveland R, Lindeman R, Demello DE, Wert SE, Whitsett JA, Perez-Atayde AR, Kozakewich H. Am J Respir Crit Care Med. 2010 Mar 4. PMID: 20203240

- A novel presentation of diffuse lung disease caused by congenital hypothyroidism. Shenoy A, Esquibies AE, Dunbar N, Dishop MK, Reyes-Mugica M, Langston C, Deladoëy J, Abu-Khudir R, Carpenter T, Bazzy-Asaad A. J Pediatr. 2009 Oct;155(4):593-5. PMID: 19773006

- Lethal respiratory failure and mild primary hypothyroidism in a term girl with a de novo heterozygous mutation in the TITF1/NKX2.1 gene. Maquet E, Costagliola S, Parma J, Christophe-Hobertus C, Oligny LL, Fournet JC, Robitaille Y, Vuissoz JM, Payot A, Laberge S, Vassart G, Van Vliet G, Deladoëy J. J Clin Endocrinol Metab. 2009 Jan;94(1):197-203. Epub 2008 Oct 28. PMID: 18957494 [Free]