Abstract
Educational Objectives
To emphasize the importance of knowing the etiopathogenesis of pediatric pathologies in order to be able to adequately guide the diagnosis and therapy in complex cases, such as in the present case.
To emphasize the need of conducting an adequate literature search when faced with a patient with overlapping signs and symptoms of 2 different pathologies to see if it has been previously characterized in the literature, as in this case.
Case Report
We present the case of a full-term male patient, son of healthy, non-consanguineous parents, with normal pregnancy course and vaginal delivery. The physical examination at birth was normal, with adequate acquisition of the first developmental milestones. At 1 year of age, the parents noticed alterations in his gaze (he looked sideways). Ophthalmologic evaluation revealed the presence of retinal acromic spots compatible with retinal hamartomas. A brain computed tomography scan was requested, which showed the presence of periventricular calcified nodules and subcortical tubers. During the first years of life, he developed multiple acromic spots on trunk, abdomen, and extremities. He presented several generalized tonic-clonic seizures. A subsequent 24-hour electroencephalogram confirmed multifocal and generalized epileptiform discharges, so antiepileptic treatment with valproic acid was started. Neuroprotective treatment with L-carnitine was also prescribed. An abdominal ultrasound at 2 years of age showed multiple bilateral cysts occupying most of the renal parenchyma. Due to the persistence of seizures refractory to medical treatment (vigabatrin, levetirazetam, topiramate, clobazam), at the age of 7 years several right parieto-occipito-temporal tubers were surgically removed (Figure 1). Over the years, the patient developed nasal angiofibromas, acrochordons in the legs, and cardiac rhabdomyomas. He also developed arterial hypertension. The last magnetic resonance imaging study, carried out when the patient was 15 years old, showed the presence of a solid tumor in the lower pole of the left kidney, characterized as probable fat-poor angiomyolipoma (Figure 2). A biopsy of the lesion was performed, which excluded malignancy. The patient is currently stable and has recently started treatment with Everolimus.
Cranial magnetic resonance imaging. The presence of subependymal nodules is observed, as well as post-surgical changes in the right occipital area.
Abdominal magnetic resonance imaging. T2 sequence. Multiple bilateral renal cortical cysts (type 1 of the Bosniak classification). In the lower pole of the left kidney, there is a hypointense solid lesion (white arrow). This lesion presented intense enhancement after contrast without subsequent washout. It was reported as compatible with an angiomyolipoma with scarce lipid component.
Discussion
Hospital Course
The genetic study by multiplex ligation-dependent probe amplification (MLPA) identified loss of dosage in the 37 probes of the PKD1 gene and the 3 probes of the TSC2 gene in the chromosomal region 16p13.3, with a total deletion of approximately 50 kb. The same study was performed to the patient’s parents and no genetic alterations were identified. With this finding, the diagnosis of TSC2/PKD1 contiguous gene deletion syndrome was established.
Discussion of the Case and Literature
Contiguous gene deletion syndrome is a condition caused by mutations in the TSC2 and PDK1 genes, which is characterized by the concurrent appearance of tuberous sclerosis and autosomal dominant polycystic kidney disease. 1 The genetic proximity of these genes, which are adjacent on chromosome 16p, justifies the concomitant occurrence of these 2 clinical entities. Generally, the onset of polycystic kidney disease appears before the renal stigmata of tuberous sclerosis. Moreover, these patients seem to present more frequently with arterial hypertension than patients with polycystic kidney disease alone, as in the case of our patient. 2 In the presence of a solid fat-poor renal lesion poor in these patients, the first diagnostic possibility is angiomyolipoma, but aggressive entities such as angiomyosarcoma should be considered in the differential diagnosis.3-5
Conclusion
In a patient with overlapping signs and symptoms of 2 different pathologies, it is imperative to perform an adequate literature search and a proper differential diagnosis, in order to identify possible infrequent syndromes. Clinical experience in pediatrics is a decisive factor in guiding the diagnosis of complex patients, as in the presented case. The presence of potential genetic alterations underlying these overlapping clinical pictures should be considered, and if there is such suspicion, genetic testing should be requested precociously. 6
Author Contributions
JAM: Conceptualization and study design, literature search, data extraction, data curation, writing—original draft, writing—review and editing. PL-P: Conceptualization and study design, writing—original draft, writing—review and editing. MBA, MV, MCS, CRA: Data extraction, data curation, writing—review and editing.
Footnotes
Acknowledgements
N/A.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Informed Consent
Verbal and written informed consent was obtained from the patient’s parents prior to submission of the manuscript.
Ethical Statement
The patients’ medical records were accessed in accordance with the specific hospital regulations applicable to this type of case.
