Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Human Genetics Department, |
RCV001089937 | SCV001244198 | uncertain significance | Bilateral sensorineural hearing impairment; Axial hypotonia; Delayed speech and language development; Progressive sensorineural hearing impairment; Abdominal distention; Loss of consciousness; Progressive gait ataxia; Atypical absence seizure | 2019-08-01 | no assertion criteria provided | clinical testing | The proband (4-year-old female) was born to an uneventful cesarean section with the birth-time weight of 3600 grams. The birth-time measured head circumference was reported as normal. She was the first child of the family, on the other hand, the second child (IV.2) was completely normal. Family history was also negative for any diseases with similar phenotypes. Following the tonsillectomy surgery, the proband gradually developed head nodding, upper limbs abnormal movements especially chorea, and then truncal hypotonia. Occasionally, she was suffering from abdominal distention and food intolerance. Down the line of the surgery, she was referred to the hospital due to neurological deterioration. The early physical and neurologic examination of the patient revealed a normal level of consciousness, normal eye contact but extraocular eye movements without any meaningful words production, truncal hypotonia with normal deep tendon reflexes and weak gag reflex. Feeding was conducted through nasogastric intubation (NG tube) at initial days of admission but gradually gastrointestinal (GI) intolerance of the patient was detectable and it was found that she was suffering from severe abdominal distension. The seizure was controlled by administrating proper anti-seizure medications. Basic metabolic tests including serum ammonia, lactate, thyroid and liver function tests, blood gas analysis, serum amino acid chromatography, MS/MS, urine organic acids profile were applied to the patient, however, all results were within normal limits. Because of suspected hearing problems, ABR was performed which revealed a severe bilateral sensorineural hearing loss in the patient, while the same condition had not been mentioned in each parent at all. As early as the first week after the patient's admission, the first brain magnetic resonance imaging (MRI) showed mild supratentorial and cerebellar atrophy with fine deep white matter signal changes in posterior area. Routine cerebrospinal fluid analysis (CSF) and CSF viral PCR for herpes simplex virus (HSV), Varicella zoster virus (VZV), enteroviruses, mumps, rubella, and measles viruses were also normal. During the hospitalization, the patient was transferred to the pediatric ICU (PICU) section due to a gradually decreased level of consciousness and also cardiorespiratory problems nothing to say GI intolerance. She was admitted to PICU for more than two months and intubated owing to a more decreased level of consciousness to Glasgow Coma Scale (GCS) score 3. Anti-seizure medications were stopped due to concern about brain death according to EEG monitoring findings. Feeding was stopped through NG tube due to progressive abdominal distension and total parenteral nutrition (TPN) was conducted to prevent nutritional imbalance. Second brain MRI, done during PICU admission, showed a progressive cerebral and cerebellar atrophy with more prominent deep white matter signal changes in posterior periventricular area. To achieve an accurate molecular diagnosis, WES was performed. Finally, the patient died due to cardiorespiratory arrest. |
| Myelin Disorders Clinic- |
RCV001254921 | SCV001426657 | uncertain significance | Neurodegeneration, childhood-onset, stress-induced, with variable ataxia and seizures | no assertion criteria provided | clinical testing |