LAUSR

We describe a 4-year-old girl with advanced Cystic Fibrosis (CF) and Coffin-Siris syndrome. Antenatally, there were concerns about Down Syndrome. She was born at term weighing 3388 g. Dysmorphic with micrognathia, broad nasal bridge, (P)iorly rotated ears, short fingers, almond-shaped eyes with thick eyelashes and fixed bilateral talipes. Genetics for Down Syndrome negative. Admitted to Neonatal Unit with stridor and obstructive breathing requiring Vapotherm. On newborn screening, identified as having CF (Delta F508/3849+10kbC >T) but pancreatic sufficient. Respiratory polysomnography confirmed partial obstruction with mixed events and microlaryngoscopy and bronchoscopy identified a retroverted larynx and laryngomalacia. In view of micrognathia, abnormal upper airways, obstructive breathing, and ventilatory support, required tracheostomy at 1 month. Successfully decannulated at 6 months. Significant global developmental delay and hypotonia apparent in the first few months and entered into the Decipher Developmental Disorders (DDD) study. Frequent respiratory exacerbations and poor growth, remaining an inpatient for the first 6 months. Port-a-cath inserted at 4 months for intravenous (IV) antibiotics. High resolution computed tomography (HRCT) chest showed significant volume loss in both lower lobes, with possible associated traction bronchiectasis. Burkholderia cepacia isolated in sputum at 7 months and Pseudomonas aeruginosa at 22 months. Aged 2 years, she required home oxygen at 1 L/min. At 3 years, bronchoscopy showed thick, copious secretions throughout inflamed airways. Bronchoalveolar lavage showed no evidence of lipid-laden macrophages, but Pandorea isolated. HRCT chest significantly progressed with extensive widespread bronchiectasis, multifocal consolidation, mosaic attenuation and peripheral tree in bud opacities. Other multisystem problems include severe gastro-oesophageal reflux, feed aversion and poor growth (weight SDS −3.09, height SDS −2.52) requiring laparoscopic fundoplication and gastrostomy at 8 months. Despite fundoplication, vomiting remains problematic. Left renal and ureteric calculi incidentally found on annual review abdominal ultrasound at 2 years requiring lithotripsy. Results from the DDD study confirmed ARID1A mutation and a diagnosis of Coffin-Siris Syndrome. Discussion In a child with CF and respiratory disease out with that expected for genotype, it is important to actively seek further diagnoses. Coffin–Siris Syndrome is a rare multisystem disorder manifested by craniofacial abnormalities, recurrent respiratory tract infections, failure to thrive, vomiting, hypotonia, developmental delay and renal or genitourinary abnormalities.