Dear colleague,
We saw on 25/07/2023 in genetic consultation the child DELAFONTAINE Nénuphrine, born on 25/07/2017 in the presence of her parents, for suspicion of tuberous sclerosis of Bourneville.
Family history:
Nénuphrine is the 3rd child of a non-consanguineous couple in good health.
Her father works as a dentist and has no notable history. He mentions that his mother had epilepsy in childhood and was treated throughout her life.
Her mother works as a librarian. She is in good health and does not mention any notable history in her family branch.
Her older sister Buccoline, aged 10, reportedly had recurrent febrile seizures between the ages of two and five, treated for three years with Valproate, and for which imaging tests returned normal.
Her younger sister Frontaline is 2 years old. The parents express concern about her as she does not yet combine words and presents repetitive movements suggestive of stereotypies.
There is no current parental project.
Personal history:
Regarding Nénuphrine, the pregnancy reportedly went without complications. She was born at term at 39 GA with measurements within normal limits. Apgar scores were 8/10, PEA +/+. There were no notable pathologies during the perinatal period.
In terms of psychomotor development, Nénuphrine crawled at 6 months, walked at 11 months, and rode a bike at 3 years. Regarding her language, she reportedly spoke her first words a bit late around 18 months. She is currently in second grade and reportedly has dyscalculia. A neuropsychological assessment is planned due to significant attentional lability.
At the age of 6, Nénuphrine had her first generalized tonic-clonic seizure, with right temporal focal spikes and waves interictally on EEG suggesting a focal lesion.
The MRI performed during this time showed signs of focal cortical dysplasia in the right sylvian valley, compatible with the EEG anomalies.
This year, the seizures recurred twice despite the early introduction of treatment with Keppra at an optimal dose. Nénuphrine is currently on a combination therapy of Lamictal and Keppra.
Dr. DECOUPE, a neurosurgeon, has seen the patient for advice regarding potential epilepsy surgery depending on the evolution of the seizures. He seeks our opinion regarding the etiology of this type of lesion.
On clinical examination today:
Nénuphrine is 7 years old, weighs 25 kg (90th percentile), measures 120 cm (+0.5 DS), and has a HC of 53 cm (+1.5 DS). On neurological examination, her osteotendinous reflexes are brisk in isolation, with no ankle clonus or Babinski sign. There are no oculomotor disturbances, no signs of ataxia, and the walking examination is normal.
Notably, on cutaneous examination, there are numerous hypopigmented macules less than a centimeter in size, reportedly attributed by the parents to childhood chickenpox, though there is some doubt as to whether all date back to that time. There are no skin plaques or facial angiofibromas. The extremities are normal, with no Koenen tumors visualized at the nail matrix. 
Please note that the father also has a few hypochromic macules on the left tibia, as well as an enamel pit at the neck of the left upper canine.
In summary:
Nénuphrine is a 7-year-old patient presenting with generalized tonic-clonic epilepsy on a focal lesion suggestive of focal cortical dysplasia. Clinical examination today shows elements that may suggest tuberous sclerosis of Bourneville.
As this is an autosomal dominant pathology with variable expressivity, we explain that it is possible that it may be inherited from one of the parents if the diagnosis were to be made. On the genetic level, we propose initially searching for pathogenic variants in the TSC1 and TSC2 genes in Nénuphrine, and we will conduct the study of her parental regressions in a second step if such a variant is identified.
We remain at your disposal for any further information.
Best regards,