*** TODO Plan
DEADLINE: <2022-05-04 mer. 19:00>
*** M

#+author: nil

* TODO BPAN

* BPAN

** Phenotype

- clinics and MRI are heterogenous : table 19.2 in[cite:@hayflick_neurodegeneration_2018]
** Early Phenotype
- described by [cite:@hayflick_beta-propeller_2013-1] : 23 patients
- initial diagnosis may be : atypical rett or epilepctic encephalopathy
- all = global developemental delay. Most had some gains over time.
  - IQ = 30-50 with expressive language severely limited
- most = broad/ataxic gait
- 13/23 epilepsy + treatement, with various types
- adolescence/early adulthood : dystonia, parkinsonism, cognitive decline (mean 25.3 years)
  - parkinsonism without tremor
  - L-dopa is effective but only for a short time
- additional features : disordered sleep (6/23), ocular defects (7/23), atypical Rett-like syndrome (7/23), bowel and bladder incontinence (most)
** Transmission
- most = de novo [cite:@hayflick_neurodegeneration_2018]
- some familial cases recorded
- male : not rare

- may be normal in early childhood
- hypointensen signal in substantia nigra, globus pallidus
- FIGURE: hypoT2, halo T1 from [cite:@hayflick_beta-propeller_2013-1]
- pathognomonic : hyperintense halo in T1 in substantia nigra and cerebral peduncles

- 3 recent reviews  [cite:@cong_wdr45_2021], [cite:@saffari_quantitative_2021], [cite:@adang_phenotypic_2020] with a 19 male cohort

- mostly central nervous system. Chronology
  1. developpemental delay/seizures
  2. brain iron accumulation
  3. Movement disorders
  4. developemental regression

- confirm the mostly neurological phenotype : developmental delay, abnormal cNS morpho, seizures
  - DI severe-profound, usually with speech disorder on the expressive or no speech
- Chronology
  1. developpemental delay/seizures in the first two years of life
  2. brain iron accumulation much later (median age = 11)
  3. Movement disorders, developemental regression, mental deterioration

- initially though lethal for male
- 3 recent reviews  [cite:@cong_wdr45_2021]

- biphasic evolution

- biphasic evolution for femail
- [cite:@saffari_quantitative_2021] seizures are more severe for male :
  - more motor seizure , especially infantile spasmes
  - more childhood onset epilpectic encphalopathies
  - more progressive encephalopathy
- but :
  - seizure not more frequent in male
  - stereotypies only in female
  - movement disorder more pronounced in female

** Our patients
- delay
- no seizures but not all reported case have them
- male are too young for movement disorder onset or regression