#+title: Memoire
#+title: WDR45 variant with a milder phenotype
#+options: toc:nil author:nil
#+bibliography: biblio.bib
* Introduction
* BPAN
** NBIA
** Early Phenotype
** Transmission
** MRI
** Therapy/management
* WDR45
** Function
** Other related diseases
* Case report
Here we report two variants in four patients. While two
** Family 1
- familial history: renal agenesis for the paternal grand-father, epilepsy in the maternal cousin of the mother
- 1 healthy sibling, French parents
*** Patient 1
  - pregnancy, birth N
  - age ??
  - neonatal: poor suckling
  - langage lay + fine motor difficulties
  - overlapping of left toes, mild hypertonia of lower limbs, mild dysmorphic features with bilateral epicanthus and hooded eyelids.
  - no epilepsy
  - metabolic, ophtalmologic, hearing N
  - MRI : bilateral and symmetric hypersignal of dentate nucleus in T2, without iron deposition
*** Patient 2 = sister
  - pregnancy, birth N
  - language delay, learning difficulties
  - round face, thick hair, short forehead and a right preaurical fistula.
  - hypermetropia and astigmatism
  - 12 years, no MRI
*** Patient 3 = mother
- learning difficulty at school
- 1 episode of depression
- autonomous in daily life but her level of education is very inferior to that of her two healthy brothers
- brain MRI (for transient visual disturbances) : left cerebellar lesion
*** Genetics testing
- CGH,FMR1, karyotype normal
- NGS : NM_007075.3 c.697C> T p.(Arg233Cys)
- de novo in the mother
- hemizygous in patient 1, heterozygus in the sistier + mother
** Family 2
*** Patient 4
- family : Algerian and French, 3 (2 ?) healthy siblings
- born 38 weeks, weight  -2.5 SD, length -1 SD, OFC
- neonatal : Suckling difficulties,  generalized hypotonia
- motor + speech delay
- No seizure
- at age 4, weigh -2SD, height -1SD,  OFC -3SD
  - no dysmorphic features.
  - axial hypotonia, pyramidal syndrome in the lower limbs, mild peripheral hypertonia and bilateral nystagmus.
- Biological workup normal
- Ophthalmologic , hearing , EEG, cardiac normal,
- MRI : dentate nucleus hyperT2, + abnormal morphology
*** Genetics testing
- CGH,FMR1, karyotype normal
- NGS : hemizygous (NM_007075.3): c.698G>T ;p.(Arg233Leu)
- de novo
* Discussion
** Phenotype
** Phenotype : male and female
** Variants
** Our patients
* Conclusion