Neonatal dicer syndrome: Case report

Authors

Abstract

DICER1 syndrome is a familial tumor predisposition syndrome resulting from genetic mutations in a gene called DICER1. This syndrome is also known as DICER1-related disorders and DICER1-related pleuropulmonary blastoma familial tumor predisposition syndrome. It is autosomal dominant, and diagnosis in the neonatal period is exceptional. Symptoms of DICER1 syndrome include abnormal growths in the lungs, kidneys, thyroid, and ovaries (for females). We report the observation of a male neonate, hospitalized at the National Referral Center for Neonatal Intensive Care and neonatology at Rabat University Hospital for neonatal respiratory distress, in whom we confirmed the diagnosis of DICER syndrome. Information and studies on this disease remain limited due to its rarity, and ongoing research is needed to better understand its epidemiology and clinical implications. It is a rare mutation that should be considered in the presence of such an association, particularly in pediatric cancers.

Keywords

Introduction

DICER1 syndrome is a rare genetic disorder caused by mutations in the DICER1 gene. It affects the microRNA maturation process and leads to various clinical manifestations, including increased predisposition to certain types of tumors. It is autosomal dominant, and diagnosis in the neonatal period is exceptional. The syndrome can affect all systems: renal, pulmonary, thyroid, genital, etc.

Case Presentation

Male newborn, macrosomic, birth weight 4260g, born past term, Apgar 8/9/9, from a 24-year-old mother, G3P3, with no particular pathological history, negative infectious anamnesis, from a 1st-degree consanguineous marriage, admitted at H9 for severe neonatal respiratory distress after a free interval (8h). The newborn was intubated and ventilated on admission. Chest X-ray revealed a homogeneous opacity occupying the left lower lobe. Thoracic CT showed a large, mixed, tissue and predominantly cystic, multi-partitioned, oval, well-limited left pleuropulmonary mass, heterogeneously enhanced after injection of contrast medium. Cerebral CT revealed subarachnoid hemorrhage, active bi-ventricular hydrocephalus, and hypoplasia of the corpus callosum.
Thyroid and abdomino-pelvic ultrasonography were ordered in search of another location, but returned normal. The newborn was extubated at D8, weaned off oxygen and discharged at 26 days of age. He underwent surgery at two months of age for resection of the pleuropulmonary mass. The anatomopathological study showed the morphological appearance of an inflammatory pseudotumor associated with calcifications.
The genetic study came back in favor of a DICER1 syndrome. Genetic counseling was carried out, with recommendations for thoracic, thyroid, digestive, renal, pelvic, and neurological monitoring for our patient and for the asymptomatic DICER1- positive parent.
Respiratory and neurological outcomes were favorable. His EEG was normal, and his psychomotor evaluation was reassuring for his age.

Discussion

DICER1 syndrome is a recent genetic syndrome, first reported in 1996 through a history of familial pleuropneumoblastomas (PPB) (1.2). It was subsequently reported as a separate entity in 2009 [3]. This rare syndrome predisposes early to PPB, cystic nephromas, ovarian Leydig and Sertoli cell tumors (SLCT), and thyroid lesions (nodules and/or multinodular goiter [MNG]). More rarely, it predisposes to pineal tumours and various types of carcinoma.
DICER1 is a gene located on chromosome 14q32 that codes for an RNA ribonuclease III involved in various biological functions. The gene comprises 27 exons [4, 5]. It is ubiquitously expressed [3]].
DICER1 syndrome is induced by a pathogenic constitutional alteration of the DICER1 gene. It is a rare autosomal dominant inherited tumor predisposition [6].
The clinical manifestations of DICER1 syndrome are diverse and include facial dysmorphia, congenital respiratory and ocular anomalies, growth retardation, cardiac malformations, renal anomalies, and in older children, a predisposition to certain tumors [7].
Pleuropneumoblastoma is the most suggestive tumor of DICER1 syndrome. It is a pediatric dysembryonic sarcoma of the lung parenchyma and/or visceral pleura. It usually occurs before the age of 6. Various types of gynecological tumors are seen, particularly ovarian [6].
Patients with a DICER1 mutation may present with various kidney lesions: cystic nephromas, anaplastic sarcomas, or Wilms’ tumors.
The most commonly reported brain tumours are pineal tumours (pinealoblastomas) and pituitary blastomas [7, 8].
The thyroid lesions most suggestive of DICER1 syndrome are multinodular goiters (MNG). At the age of 40, 75% of women and 17% of men present with MNG or thyroidectomy.
Diagnostic confirmation is often based on in-depth genetic analysis, including DNA sequencing.
Multidisciplinary management is crucial. Treatment is mainly symptomatic, with an individualized approach based on each patient’s specific clinical manifestations [8].
There is little data on DICER1 syndrome, which limits the availability of precise recommendations. However, a few monitoring protocols have been published. In general, regular follow-up with chest imaging is recommended from birth to age 12. Abdominal and pelvic ultrasound scans during childhood are used to look for kidney and gynecological disorders, although the age at which monitoring ends is not clearly defined. Thyroid function monitoring is also recommended. Ophthalmological, ENT and brain MRI examinations are discussed on a case-by- case basis, depending on the patient’s symptoms and individual needs [1, 2].

Conclusion

Although DICER1 syndrome can affect newborns in rare cases, it is generally considered a rare disease that manifests more frequently later in childhood or adolescence. The DICER1 syndrome is, therefore, in the process of being characterized and now includes many more tumors than those initially described. Indications for screening are expanding, and surveillance recommendations are better defined. Ongoing research is needed to better understand its epidemiology and clinical implications.

References

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