Dear Colleague,
I met today, on 26/08/2023, at the request of Dr. RLOHF, Mrs. Bépane NOYONFER, born on 15/02/2000, to explore the possibility of a genetic etiology in the context of severe intellectual disability associated with Lennox-Gastaut type epilepsy.
Mrs. NOYONFER is the 2nd child in a sibling group of three, with two adult brothers currently in good health.
The father, Mr. Enbi NOYONFER, born on 12/03/1975, is in good health.
The mother, Mrs. Aï’a NOYONFER, born on 20/08/1970, is in good health, although she is on long-term treatment for hypothyroidism and hypertension.
There is no history of spontaneous miscarriage or consanguinity in Bépane's parents, noting that they are both from the same village in northern Canada.
Regarding Bépane, we have limited information about her perinatal history:
A normal pregnancy and delivery at 38 GA with a birth weight of 3.2 kg and a birth length of 52 cm.
Around the age of 12 months, she experienced a febrile episode with cyanosis, followed by the onset of epilepsy with eyelid clonus and head drop. Upon her arrival in France in 2007, she was managed for Lennox-Gastaut type epilepsy by Dr. RLOHF with trials of several antiepileptics, without notable improvement. A cerebral MRI in 2007 showed global cerebral atrophy with a thin corpus callosum. Bilateral involvement of both pallidums was noted, though the nature of this involvement was unspecified. The cerebral CT scan did not show calcifications.
Her autonomy remains very limited; she is non-verbal and non-ambulatory, with movements primarily assisted by a wheelchair.
Previous explorations:
A broad metabolic assessment in 2008 showed no significant anomalies.
Genetic testing: Normal standard karyotype (46,XX) and negative fragile X test.
Currently, she has been on Cannabidiol for 2 months, which appears to show promising results, with a decrease in seizure severity and frequency.
Clinical examination on 26/08/2023:
W: 62 kg, H: 1.38 m, HC: 55 cm.
No particular dysmorphia. Oral examination shows no obvious anomalies. No evident skin anomalies. Abdominal palpation and pulmonary auscultation were challenging due to limited cooperation.
Neurological findings: No dystonic elements suggestive of extrapyramidal syndrome. Spasticity is noted on the left side with a flexion deformity of the left knee. Deep tendon reflexes are present in the upper limbs but absent in the lower limbs. A bilateral Babinski sign is present, and the Hoffmann sign is absent.
Overall, the findings suggest a genetic etiology, particularly involving genes responsible for intracerebral iron overload (NBIA).
I propose performing a trio exome analysis after obtaining consent for the analysis of constitutional genetic characteristics in Bépane. The family understands that this will not significantly alter management but may provide more precise genetic counseling.
I will keep you informed of the results, which should be available in a few months.
Best regards.