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PP-090 Brain-lung-thyroid syndrome: neonatal phenotype of de-novo NKX2.1-related disorder
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  1. Swati Pakolu,
  2. Adina de Coverly,
  3. Kumar Somasundaram
  1. Tunbridge Wells Hospital, Maidstone and Tunbridge Wells NHS Trust

Abstract

Aim We present a rare, genetically heterogenous, de-novo NKX2.1-related disorder in a neonate

Material and Method Brain-lung-thyroid syndrome, is a rare genetic syndrome.1 It is caused by autosomal dominant mutations in the NKX2-1 gene (previously TTF-1), on chromosome 14q13, which encodes for a particular transcription factor, critical for the development of the brain, lung and thyroid.2 It is a genetically heterogeneous condition, with over 30 different causative mutations identi ed.3 The syndrome is also referred to recently as NKX2.1-related disorders, due to the varied manifestations noted in heterozygous mutations, including benign hereditary chorea[BHC] which is a hallmark feature, while some can develop choreoathetosis, tremors, motor & vocal tics as well.4 Classic triad of the syndrome includes Congenital hypothyroidism, Benign hereditary chorea and Respiratory distress syndrome in infancy. Approximately 50% of the patients have a complete triad involved, while about 30% are affected by neurological and hypothyroidism phenotype and about 13% may only present with neurological phenotype. The overall prognosis varies depending on the presenting phenotype and severity of symptoms with respiratory involvement having the most impact on survival in some patients.5 We present a term neonate admitted in the neonatal intensive care unit for respiratory distress with incidental finding of macroglossia leading to diagnosis of congenital hypothyroidism with hypertonia at birth, with childhood Interstitial lung disease [figure 1]; eventually diagnosed as heterozygous for the pathogenic deletion of the entire coding region of NKX2-1 gene including the promoter region, de-novo mutation.

Abstract PP-090 Figure 1

CT Thorax: Ground glass appearance suggestive of childhood interstitial lung disease

Results We present a term neonate admitted to the neonatal intensive care unit for respiratory distress with incidental finding of macroglossia leading to diagnosis of congenital hypothyroidism with hypertonia at birth, eventually diagnosed as heterozygous for the pathogenic deletion of the entire coding region of NKX2-1 gene including the promoter region, de-novo mutation.

Conclusions High index of suspicion is required in neonates with congenital hypothyroidism and respiratory distress syndrome to determine an underlying genetic etiology. Life expectancy in individuals with NKX2-1-related disorders is expected to be normal with supportive management.

  • : Brain-lung-thyroid
  • Childhood Interstitial lung disease
  • Congenital hypothyroidism
  • Hypertonia
  • NKX2-1-related disorders

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