First classified in 1912 by Scheider, the pulmonary hypoplasia is a rare inborn lung underdevelopment, resulting in reduced airways, alveoli, and pulmonary parenchyma [1]. This impairs respiratory function and oxygen exchange, often leading to significant neonatal morbidity and, in severe cases, mortality [2]. While primary idiopathic pulmonary hypoplasia is rare, the condition is usually secondary to other fetal abnormalities that restrict lung growth. These include congenital diaphragmatic hernia, oligohydramnios, skeletal dysplasias, and thoracic compression. Lung development is a complex process influenced by mechanical forces, amniotic fluid volume, and intrauterine space. The severity of pulmonary hypoplasia largely is impacted by the timing and nature of these disruptions, particularly during the pseudoglandular stage (5–17 weeks of gestation), when branching morphogenesis and airway formation occur [3]. As the lungs play a critical role in oxygenation, pulmonary hypoplasia can place additional strain on the cardiovascular system, potentially leading to complications such as pulmonary hypertension [4]. Understanding the underlying causes and developmental mechanisms of this condition is essential for improving prenatal interventions and neonatal care.
A 11-years-old boy with complaints of frequent infectious diseases was admitted. First manifestations started at 1.5-month age with cold. Also, he had recurrent fever, sinusits, otitis and pneumonia. He is the first child from non-consagenious parents. His sibling, 5-years-old girl is healthy. No prior cases in family history. In 2016, the patient was admitted to hospital with complaints of cough and short breath. Auscultation had established harsh breath and moist rales with weakened breath sounds in the lower lung fields. Heart tones were clear and rythmic. Ultrasound test observed a hepatosplenomegaly. Based on bronchoscopy and bronchography, the hypoplasia of basal lung segments was diagnosed. As a treatment, plasma transfusion, antibacterial, antifungal and antiviral therapies, vitamins, expectorant mucolytic and antihistamine agents were prescribed.
Ultrasound Examination of Organs in June 2021: Liver: Right lobe: CRD (craniocaudal dimension) 134 mm. Left lobe: CC (craniocaudal) 81 mm. Liver size increased by 4 cm, contours smooth and well-defined. Parenchyma homogeneous, normal echogenicity, granularity within normal limits. Arterial and venous vascular patterns preserved, not deformed. Portal vein: 4 mm, not dilated. Portal vein blood flow in Doppler mode: 27 cm/sec. Inferior vena cava: 8 mm, not dilated. Gallbladder: Pear-shaped, contents consist of homogeneous fluid. After breakfast, the gallbladder measures 84×19 mm, enlarged, slightly deformed. Walls unevenly thickened, wall thickness: 2 mm. Intrahepatic bile ducts: not dilated. Common bile duct: 3 mm. Spleen: Kidney-shaped, size 136×45 mm, enlarged. Contours were smooth and well-defined. Parenchyma homogeneous, normal echogenicity. Vascular pattern preserved, without abnormalities. Splenic vein: 8 mm, not dilated.
In 2023, the immunophenotyping was performed: T cells 62%, CD4+T cells 50%, CD8+T cells 44%, B cells 12%, NK cells 7%. IgG 7.96 g/l, IgA 1.5 g/l, IgM 1.9 g/l. In 2024, IL-6 was elevated (24 pg/ml). And in 2024, immunophenotyping was repeated: T cells 66%, CD4+T cells 50%, CD8+T cells 28%, B cells 14%, NK cells 16%. IgG 16.8 g/l, IgA 1.76 g/l, IgM 1.74 g/l. Next year, he was admitted to hospital with complaints of cough, fever and fatigue. Clubbed fingers were observed. No-shpa, diphenhydramine, calcium gluconate and Reosorbilact were prescribed. Afterwards, primary ciliary dyskinesia was suspected and genetic test recommended, which has revealed that in DNAI1 and other genes associated with primary ciliary dyskinesia (DNAAF1, DNAAF2, DNAAF3, DNAAF4, DNAAF5, DNAH1, DNAH11, DNAH5, DNAI2, DNAL1) pathogenic variants weren’t identified [5].
In June 2024, he was admitted to hospital with complaints of swelling and reddening of a right eye. Abscessing phlegmon of the lacrimal sac and recurrent blepharitis were diagnosed. A strain of staphylococcus resistant to cefoxitin, aminoglycosides, erythromycin, and trimethoprim-sulfamethoxazole was identified in a sample from the conjunctiva. In the right eye, there was significant swelling and hyperemia of the lower eyelid skin, with a narrowed palpebral fissure. In the area of the lacrimal sac at the inner corner of the lower eyelid, there was a purplish-colored lesion with a crusted surface, measuring 3.0 × 3.0 mm. The eyelid edges were deformed, swollen, and painful. When pressing on the lacrimal sac area, an induration and tenderness were noted. There was a mixed injection of the conjunctival and episcleral vessels. The cornea was clear, and the anterior chamber was of medium depth. The pupil was round, centrally positioned, and reacted to light. The lens was clear. A pink reflex was visible from the fundus. The edges of the left eyelid were deformed and swollen. The ocular media were transparent. A diagnosis of chronic catarrhal sinusitis was established. An orbital X-ray showed no bone-destructive changes. The following treatment was applied: Under local anesthesia, an abscessing phlegmon of the lacrimal sac was incised and drained. Daily wound care was performed, leading to wound clearance. Prescribed medications: Ceftriaxone Metrogyl (Metronidazole) Dexamethasone Erythromycin ointment.
Although the Inborn Errors of Immunity panel did not identify any pathogenic variants, computational analysis of a missense variant in the SAMD9L gene suggests potential functional disruption.This sequence change substitutes asparagine with threonine at codon 1193 of the SAMD9L protein (p.Asn1193Thr). Both amino acids are neutral and polar. Considering factors such as structural integrity, functional domains, spatial configuration, amino acid conservation, physicochemical properties, residue mobility, and thermodynamic stability, predicts an 80% likelihood that this variant impairs SAMD9L protein function. The disruption of SAMDL is associated with malignancies, as this protein is considered as tumor suppressor [6,7]. However, the patient wasn’t diagnosed with any oncology, the influence of this potential pathogenic variant seems uncertain.
