Rare pathology caused by alteration in EXOSC9 gene

*Correspondence: [e-mail].

Abstract

Case Presentation: G. T. S. D. S., 1 year and 2 months old, male patient, diagnosed with the rare condition of Pontocerebellar Hypoplasia Type 1D (PCH1D), resulted from an alteration in the EXOSC9 gene. Son of non-consanguineous parents. Prenatal care was complete. The patient was born by vaginal delivery without complications, at 36 weeks and 6 days of gestational age, with the following measurements: height = 44.5 cm, weight = 2660 kg, head circumference = 33.8 cm.

Discussion: At 2 months old, the first symptom was noticed: looking up fixedly. The investigation began: electroencephalogram, cranial computed tomography and cranial magnetic resonance - all within normal results. The family consulted a geneticist who ordered screening tests for inborn errors of metabolism. All with unchanged results. After 3 months, he started rehabilitation and showed improvement: he still could not support his head by himself, but was able to rotate his neck. At 6 months-old he started having several spasms during the day. Valproic acid was administered, but adverse reactions of drowsiness caused it to be discontinued before 1 month of use, vigabatrin was introduced and after one month the spasms completely ceased. Currently, the patient remains under specialized follow-up and uses vigabatrin 500 mg daily. Exome sequencing test and a new magnetic resonance imaging were performed and respectively evidenced a homozygous variant of the EXOCS9 gene (NM_001034194.1: c.41T>C-p.Leu14Pro) and pontocerebellar hypoplasia. After 7 months, he stopped gaining weight which demanded follow-up with gastropediatrics and nutritionist. He has since required a gastrostomy to be able to receive a complete diet.

Final Comments: Besides the present case, only 10 others with the same variant in the EXOCS9 gene (NM_001034194.1: c.41T>Cp.Leu14Pro) were reported, which represents 60% of the total reported cases of Pontocerebellar Hypoplasia Type 1D (PCH1D). It is a severe autosomal recessive neurological disorder characterized by severe hypotonia and an apparent motor neuronopathy, and also includes severe delay in gross motor development. Patients may present slow growth rates, contractures, eye movement abnormalities, respiratory failure and feeding difficulties, and epilepsy. The case highlights the importance of the molecular study for both predicting prognosis and for family orientation in similar situations.

Publication History

Article published online:
12 May 2025