Rare Presentation of Schizophrenia in a Patient with Congenital Right Lung Agenesis: A Case Report

Dear Editor,

Early life trauma (obstetric complications) and dysmorphogenesis are hypothesized to increase the risk of schizophrenia at a later age. ¹ Minor physical anomalies (MPA) are proposed to be an endophenotype of schizophrenia, and a recent meta-analysis showed a significant difference in the presence of MPA among schizophrenia patients compared to healthy controls.^2,3 Literature regarding the presence of major congenital malformations in patients with schizophrenia is sparse. Lung agenesis is a rare congenital condition, and half of these cases are associated with abnormalities in other systems, such as cardiovascular, genitourinary, gastrointestinal, and skeletal abnormalities. In cases with unilateral lung agenesis, the condition can present at any age depending upon the presence or absence of other anomalies, and the majority have a history of recurrent respiratory infections.^4–7 To the best of our knowledge, there is no published literature describing the association between lung agenesis and schizophrenia.

We report a case of a 22-year-old male who had congenital right lung agenesis and schizophrenia. Informed consent was obtained from the patient.

Case Presentation

The patient is a 22-year-old male, Bachelor of Pharmacy student, who presented with a two-year duration of illness with insidious onset, continuous course without any elicitable precipitating factor. His illness was characterized by symptoms of irritability, aggression, academic decline, increased religiosity, hearing voices, muttering to self, fear of being controlled by someone, poor oral intake, weight loss, and disturbed sleep.

As per the mother, the antenatal period was uneventful. The patient was born out of full-term vaginal delivery in the hospital and cried immediately after birth. Given multiple anomalies related to lung and kidney, he was in the neonatal intensive care unit for a few days; exact details are not available. After that, till one year of age, the patient had repeated respiratory tract infections and admissions for the same.

There was no history of seizures and drug allergy. No history of psychiatric illness in childhood or in the family.

Mental state examination showed muttering to self, auditory hallucinations, delusion of control, and thought broadcasting with grade III insight. He was admitted to the ward for further workup. Given his systemic findings, aripiprazole was started at 2.5 mg, and the dose was optimized to 10 mg during the admission. Neurological examination was within normal limits.

Systemic Examination, Investigations, and Consultations

Consultation was sought from the pediatrics, pulmonology, cardiology, and nephrology departments. Routine blood investigations were within normal limits. A pediatrician evaluated the patient and advised genetic analysis for syndromic assessment, which could not be done due to affordability issues. Ophthalmology and otorhinolaryngology evaluations were within normal limits.

Cardiovascular examination showed the apex beat on the right side of the chest wall in the infraclavicular area, medial to the midclavicular line. Heart sounds were appreciated on the right side of the chest. There was no murmur, thrill, or heave. Echocardiography was suggestive of dextrocardia with mild pulmonary artery stenosis. No active intervention was advised from the cardiology side. The pulmonologist suggested a CT chest, which was suggestive of right lung agenesis, hyperinflated left lung, bronchiectasis changes, and mediastinal shift toward the right (Figure 1). Symptomatic treatment was given along with chest physiotherapy. A nephrologist’s opinion was sought. The USG abdomen showed an absent left kidney and right pelvic kidney; urine culture was negative for any growth. An orthopedic referral was sought, an impression of neglected congenital torticollis was made, and a liaison with the physiotherapy department was suggested. The brain MRI was also within normal limits.

Figure 1.

CT Chest Showing Right Pulmonary Agenesis, Hyperinflated Left Lung and Mediastinal Shift to the Right.

Discussion

In this article, we described the co-morbid occurrence of schizophrenia in a patient with major congenital malformations. Developmental insults in the late first or early second trimester lead to dysfunction in the neural circuits during adolescence or early adulthood, leading to the development of schizophrenia. ⁸ Despite this evidence, the specific mechanism by which all these factors increase the risk for schizophrenia is not known but may represent some maldevelopment of the fetus. Congenital anomalies of the brain, such as agenesis of the corpus callosum, stenosis of the Sylvian aqueduct, and cavum septum pellucidum, were found more commonly in schizophrenia patients. As these anomalies are due to defective organogenesis in the second trimester, this further strengthens the “neurodevelopmental” hypothesis of schizophrenia.^2,4

The presence of major congenital malformations since childhood in the index patient before the development of schizophrenia in early adulthood aligns with the developmental theory of schizophrenia. Several genetic syndromes were shown to be frequently associated with schizophrenia, such as Niemann Pick type C disease, DiGeorge/velocardiofacial syndrome, DISC1 [t(1;11) (q42;q14)] mutations, etc. In most, but not all, of these syndromes, patients have dysmorphic facial features along with mild to severe levels of intellectual disability. The genetic abnormality in the syndromes mentioned above predisposes the individuals to the development of early-onset schizophrenia (<18 years) more often than not. ⁹ However, the index patient did not have intellectual disability or any other features of these genetic syndromes. Studies have also shown that patients with congenital lung anomalies are at a higher risk of neurocognitive impairments such as executive functions, memory, attention, visuospatial processing, memory, and motor functions, which are also seen in patients with schizophrenia. ¹⁰

Another possible explanation for the development of schizophrenia in the index patient is exposure to recurrent respiratory infections during the “critical neurodevelopmental period,” leading to increased risk for psychopathology via inflammatory mechanisms or neuroinvasive properties of these viruses. ¹¹ Viral infections in neonates, children, and adolescents have been associated with later development of schizophrenia. A similar association between respiratory infections and psychotic disorders was also reported during the COVID-19 pandemic. ¹¹

To our knowledge, this is the first article that described the occurence of schizophrenia in a patient with congenital right lung agenesis, dextrocardia, and solitary pelvic kidney. We acknowledge that detailed genetic analysis could not be carried out on our patient for reasons described earlier. This highlights the fact that individuals with major congenital anomalies may be at an increased risk of schizophrenia/psychotic disorders. Regular screening and liaison with psychiatrists help in the early detection and holistic management of the disorder. Detailed genetic analysis may help in better conceptualization of the developmental underpinnings of both schizophrenia and congenital malformations.