Abstract

Genetic causes of children interstitial lung disease (ChILD) represent close to 20 % of the cases. We present here the first case of ChILD associated with 48, XXYY syndrome.

An 11- months-old boy was admitted to investigate a chronic dyspnea with cough and failure to thrive. His medical history was unremarkable with respect of transient neonatal respiratory distress in a full-term baby. Physical exam at presentation revealed chest wall retraction, basolateral scattered wet crackles and mild hypoxemia requiring nocturnal supplemental oxygen. Metabolic and infectious investigations were unremarkable as were thyroid function and cardiologic assessments. High resolution CT (HRCT) scan was performed showing bilateral ground glass opacities. Monthly intravenous methyl prednisolone pulses were initiated. Despite respiratory function improvement with lower respiratory rate, improvement of chest retraction and weaning of oxygen therapy, HRCT worsened with persistent diffuse bilateral ground-glass opacity. Genetic screening for inherited surfactant metabolism disorders was performed. Interestingly, no mutation was detected in surfactant genes, but search for NKX2-1 large rearrangement by MLPA technology, using probes in chromosomes X and Y as controls, highlighted the presence of excessive genetic material suggesting the abnormal karyotype 48, XXYY, which was further confirmed by cytogenetic method. After 16 months of bolus methylprednisolone therapy, respiratory condition and imaging significantly improve. Besides, developmental delay and cognitive problems were noticed. Overexpression of the CSF2RA gene (GMCSF receptor) located in the pseudoautosomal region of the X and Y chromosomes may explain the lung phenotype.