CRP6 CYSTIC FIBROSIS IN A CHILD WITH 49,XXXXY: A CASE REPORT

Hui Chean E1, Sok Bee LIM1, Asiah KASSIM2
3.Department of Paediatrics, Hospital Melaka, Malaysia.
4.Department of Paediatrics, Hospital Tunku Azizah, Kuala Lumpur, Malaysia

Introduction: 

49,XXXXY syndrome is the rarest X chromosome aneuploidy with approximate incidence of 1:85,000-1:100,000 male births. Cystic fibrosis (CF) is an autosomal recessive disease which is also uncommon among the Asian population. CF is associated with more than 1500 gene mutations in which delta-F508 mutation being the most common. 

Case report:

We present a case of a Malay boy aged 10.5 years old who was born prematurely to a pair of non-consanguineous parents. He had soft dysmorphism at birth, later diagnosed as 49,XXXXY at 14 months old with multiple associated anomalies; intellectual impairment, congenital heart defects, severe myopia, moderate hearing impairment and faltering growth. During his early years, he had recurrent pneumonia and subsequently diagnosed as post infectious bronchiolitis obliterans requiring home oxygen therapy from 9 months to 3 years old. When he was 9, he was noted to have progressive digital clubbing with persistent crepitations. Further respiratory assessment revealed positive sweat test of 60 mmol/L with HRCT thorax suggestive of chronic pneumonitis of infancy which may represent childhood interstitial lung disease. PID screening showed low NK cells with normal T&B cells and immunoglobulin level. Bronchoscopy and faecal fat globule were normal. Whole exome sequencing found no mutation that could be linked to cystic fibrosis or other lung diseases in this child. 

Conclusion:

Comorbidity of these two disorders has not been previously reported. More data of male of with 49,XXXXY is needed to determine association with respiratory condition and its long term outcome. This may aid subsequent development of appropriate therapies, multidisciplinary support and genetic counselling for families.