Background: A variety of syndromes are known to be associated with immune deficiency, some as a major part of the syndrome and some as an occasional finding. Objective: To report a newly defined syndrome of hydrocephalus, hypoplastic sinuses, cartilaginous webbing of the bronchi, bronchiectasis, and hypogammaglobulinemia with functional antibody deficiency in identical twin girls. Methods: Spirometry, radiography, computed tomography (CT), bronchoscopy, and laboratory tests were performed for diagnosis. Results: A girl (twin A) was evaluated at the age of 7 years for chronic cough and wheeze that worsened with exercise, i Hydrocephalus had been diagnosed a year before evaluation. She was treated for cough variant asthma and was lost to follow-up until the age of 10 years. The cough had worsened progressively, and dyspnea was now apparent. Spirometry was consistent with reversible airway obstruction. A chest radiograph was suggestive of bronchiectasis. A chest CT scan showed bilateral upper lobe bronchiectasis. Hypogammaglobulinemia and functional antibody deficiency were noted. A CT scan of the sinuses revealed aplasia or severe hypoplasia of all the paranasal sinuses. Bronchoscopy revealed a grossly abnormal bronchial structure and atrophic-appearing bronchial mucosa. Twin B also had a history of hydrocephalus. Although she had no respiratory symptoms, chest CT revealed bronchiectasis, and she had obstruction on spirometry. Laboratory analysis revealed hypogammaglobulinemia and functional antibody deficiency. She became symptomatic 2 years after twin A. Conclusions: This is a newly reported syndrome of hydrocephalus, absent sinuses, abnormalities of the bronchi, and functional antibody deficiency, which initially presented as cough and wheeze.