Can Coffin-Siris Syndrome Cause Chronic Cough?
No, Coffin-Siris syndrome does not directly cause chronic cough based on available evidence. Chronic cough is not a recognized feature of this genetic disorder, and respiratory symptoms are not part of its core clinical presentation.
Core Features of Coffin-Siris Syndrome
Coffin-Siris syndrome is a rare genetic disorder with well-defined clinical characteristics that do not include chronic cough:
Primary manifestations include intellectual developmental disorder, distinctive facial features, fifth digit nail or distal phalanx hypoplasia/aplasia, sparse scalp hair with hirsutism elsewhere, and congenital malformations 1, 2
Neurological and behavioral features include borderline to severe intellectual disability, behavioral issues, speech and language impairment, and potential autism spectrum disorder 1
Cardiovascular and other organ involvement may include congenital heart defects (such as hypoplastic right ventricle, VSD, truncus arteriosus), but respiratory tract abnormalities causing chronic cough are not described 3
Long-term prognosis appears compatible with survival into older age without progressive chronic respiratory illness, as demonstrated in a 69-year-old patient with CSS who had no evident history of chronic illness 2
When to Consider Other Causes of Chronic Cough
If a patient with Coffin-Siris syndrome presents with chronic cough, evaluate for the common causes that affect the general population:
Upper airway cough syndrome (UACS) is the most common cause of chronic cough and should be considered first, even in patients with genetic syndromes 4
Asthma and non-asthmatic eosinophilic bronchitis are frequent causes that respond to inhaled corticosteroids 5, 6
Gastroesophageal reflux disease (GERD) can cause chronic cough without typical heartburn symptoms in up to 75% of cases 7
Chronic bronchitis from environmental irritants or smoking should be excluded 4
Clinical Approach
The presence of chronic cough in a patient with Coffin-Siris syndrome should prompt a standard chronic cough evaluation rather than attributing it to the genetic syndrome itself. The diagnostic approach should include:
Systematic empiric treatment for UACS, asthma, and GERD, as these account for the vast majority of chronic cough cases 6, 8
Chest radiography to exclude infectious, inflammatory, or malignant conditions 6
Consideration of medication-induced cough (particularly ACE inhibitors) 5, 8
Pulmonology referral if cough persists despite sequential empiric therapy 5