Choreoathetosis, Hypothyroidism, and Neonatal Respiratory Distress (also known as Brain-Lung-Thyroid Syndrome or sometimes TTF1-deficiency Syndrome in older literature) involves (as originally characterized) the brain, lungs, and thyroid to variable degrees.  All three organs do not need to be affected to consider the diagnosis.

Neurologic symptoms include chorea, choreoathetosis, hypotonia and ataxia.  Developmental delays, both global and motor, and mental retardation have also been reported.  Hypothyroidism (sometimes compensated and not overt; as measured by elevated serum thyrotropin) is present in most patients, though the size of the thyroid can be small to normal.  Thyroid agenesis has also been reported.  Lung disease manifests as neonatal respiratory distress that can be fatal or recurrent pulmonary infections.  A significant number of surviving patients go on to develop chronic interstitial lung disease.  Though lung disease is the most infrequent symptom, it accounts for significant patient mortality. 

In one literature review, 50% of patients had brain, lung and thyroid findings; 13% had benign chorea only, and 6% had thyroid and lung or thyroid only symptoms. 

Of 56 patients included in two published series, 10 had NKX2-1 mutations (18%).  Of the identified mutations, two were gene deletions and 8 were point mutations identifiable by gene sequencing.  Sequencing of the NKX2-1 gene is predicted to detect a mutation in approximately 14% of symptomatic patients.  MLPA analysis is predicted to detect a mutation in approximately 4% of patients. 

Analytic Sensitivity:   

MLPA:  Analytical sensitivity for deletions is estimated to be at least 90%.
 

MLPA: $429 for routine testing on a blood or DNA sample
83896 x 3
83900 x 1
83909 x 1
83914 x 1
83912 x 1

Please contact the lab to arrange testing for known mutations on blood or prenatal samples.