# Idées
## OPHN1
Biblio :
- combien d'articles
- quelle dysmorphie ?
### @nuovo2021 : 3 hommes + 1 femme (+ hypoplasie cérébelleuse). Photos : 2 garçon
Carrier females are usually unaffected, probably due
to protective skewed inactivation of the X chromosome; nevertheless,
some paucisymptomatic females have been reported (most with a ran-
dom pattern of X inactivation), typically showing mild ID, minor cere-
bellar anomalies or strabismus (Boglis ̧ et al., 2020; Des Portes
et al., 2004; Iida et al., 2018; Moortgat et al., 2018; Schwartz
et al., 2019; Zanni et al., 2005).(
Patient 1: Facial dysmorphism was evident, including long face with prominent fore-
head, hypotelorism, deeply-set eyes, protruding ears, long nose, short
philtrum, thin upper lip and broad chi
frère) idem
cousine : (0 photos) same subtle dysmorphic features
patient autre famille : mild dysmorphic features, includ-
ing prominent ears, thin upper lip, full lower lip, and broad eyebrow
### @boglics20203 garçons
3 male : facial dysmorphism with a prominent forehead, long face, nystagmus, convergent strabismus, deep-set eyes, prognathism, and a prominent nose.
he facial features associated with OPHN1 syndrome reported by Ronzoni et al and Al-Owain et al comprise prominent supraorbital ridges, deep-set eyes, hypotelorism, thin upper lip, prognathism, and a short philtrum.[9,18] Only subject III-16, in our family report, presents the prognathism and deep-set eyes.
Strabismus represents a sign found in approximately 90% of previous reported OPHN1 mutations and is present in both investigated children.[3,8,9,15,16,18,20–23] Nystagmus has been described by Moortgart et al,Schwartz et al, and Zanni et al,[8,21,24] and it is also present in the proband (III-16). The facial dysmorphism seen in almost all affected patients could be explained by the expression of OPHN1 in the craniofacial bones.[24] Tall stature and macrocephaly have also been described in different families,[19] but not present in our investigated subjects (III-16, IV-2).
## Schwartz 2020 3 patients
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6310103/
Common Features of OPHN1 Reported in the Literature % (n) Our Study % (n)
Distinctive facies 84 (37/44) 100 (3/3)
Cerebellar hypoplasia 80 (35/44) 67 (2/3)
Ventriculomegaly 80 (36/45) 67 (2/3)
Strabismus 76 (29/38) 67 (2/3)
Genitourinary abnormalities 54 (14/26) 0 (0/3)
Behavioral Disorder 52 (17/33) 67 (2/3)
Seizures 43 (23/53) 100 (3/3)
Ataxia 40 (16/40) 100 (3/3)
Cf tableau pour dysmorpho des études
|Study Cohort|Patient 1|Patient 2|Patient 3|Moortgat 2018|Busa, 2017|Santos-Reboucas, 2014|Al-Owain, 2011|Madrigal, 2008|Zanni, 2005|Chabrol, 2005|des Portes, 2004|Philip, 2003|Bergmann, 2003
|Patient Profile||||A|B|C|D|||||A|B|C|D|||A|B|
|Age (years)|22|5|6|13,9,62,66|15,10|50,49,48,45,42, 27|7|7|8,4,33,18|19,17,15,2|NA|6|9, NA|NA,NA,4,27|8, NA|22,16 mo.|59,25,14,5|18,14,NA|13|21,20,13,5,2
|Variant|c.T590A |p.V197Ea|c.549dupT |p.Q184fsa|c.G2035A |p.D679Na|c.384+3A→C |p.V105_K128del|c.697C→T |p.Q233*|c.727C→T |p.R243W|c.1235G→A |p.G412D|Del Ex 3-15|Del Ex7|Del Ex7-15|Del 21+22|c.154+2T→C |p. ?|Del Ex 16+17|c.556C → T, p.Q186*|c.1645C→T, p.Q549*|c.644_645del |p.V215Gfs*35|Del Ex 19|c.745_752dup |p.K251Nfs*6|c.184C→T |p.Q62*|Del Ex19
|de novo|Yes|Yes|No|No|No|No|Yes|NA|No|No|No|No|No|No|No|No|No|No|Yes|No
|Macrocephaly|−|−|−|−,NA|−,−|−,−,−,−,−,−|−|−|−,−,−,−|NA|NA|NA|NA|+,+,NA,NA|−,−,−|NA|−,−,−,−|+,+,NA,+|+|−,−,−,−,−
|Prominent forehead|−|−|−|NA|NA|−,−,−,−,−,−|−|NA|+,+,−,−|+,+,+,+|NA|NA|NA|NA|NA|NA,+|NA|NA|NA|NA
|Long face|+|−|−|NA|+,−|−,−,−,−,−,−|−|NA|NA|+,+,+,+|+,+,+,+|NA|NA|+,+,NA,NA|+,+,+|+,NA|NA|+,+,+,+|NA|NA
|Short philtrum|+|−|−|NA|NA|−,−,−,−,−,−|−|NA|NA|NA|NA|NA|Mi.,+,+,+,+,+|+,+,NA,NA|+,+,+|NA|NA||+|NA
|Marked infraorbital creases|+|−|−|NA|NA|−,−,−,−,−,−|−|+|NA|NA|NA|NA|NA|NA|NA|+,+|NA|+,+,+,+|+|NA
|Prominent chin|−|−|−|NA,NA,+,+|+,−|−,−,−,−,−,−|+|NA|Mi.,+,+,Mi.|+,+,+,+|+,+,+,+|NA|Mi.,+,+,+,+,+|+,+,NA,NA|+,+,+|NA|NA|+,+,+,+|+|NA
|Large ears|+|−|−|NA|NA|−,−,−,−,−,−|−|NA|+,+,+,−|+,+,+,+|NA|NA|NA|NA|NA|+,+|NA|NA|NA|NA
|Hypotelorism|−|−|−|NA|NA|−,−,−,−,−,−|−|NA|−,−,−,−|NA|NA|NA|Mi.,+,+,+,+,+|+,+,NA,NA|+,+,+||NA|NA|NA|NA
|Deep-set eyes|−|−|+|+,+,−,−|−,−|−,−,−,−,−,−|−|NA|+,+,+,Mi.|+,NA,NA,NA|NA|NA|Mi.,+,+,+,+,+|+,+,NA,NA|+,+,+|+,NA|NA|+,+,NA,NA|+|NA
|Long, tubular nose/Prominent nasal root|−|−|+|NA|+,−|−,−,−,−,−,−|−|NA|+,+,+,+|+,+,+,+|+,+,+,+|NA|Mi.,+,+,+,+,+|+,+,NA,NA|+,+,+|NA|NA|NA|+|NA
|Thin upper lip|−|−|−|NA|NA|−,−,−,−,−,−|−|NA|NA|NA|NA|NA|Mi.,+,+,+,+,+|+,+,NA,NA|+,+,+|NA|NA|NA|NA|NA
|Strabismus|+|+|− (pseudo)|+,+,+,+|−,−|−,−,−,−,−,−|+|+|+,+,+,−|+,+,+,+|+,+,+,+|+|NA|NA|NA|+,+|+,+,+,+|NA|NA|+,+,+,+,+
|Nystagmus|+|−|−|+,+,NA|NA|−,−,−,−,−,−|−|−|NA|NA|NA|+|−,+,+,+,+,+|NA|+,+,+|NA|NA|−,−,−,−|−|NA
|Genitourinary
|Genitourinary abnormalities|−|−|−|NA,+,NA|NA|NA|NA|NA|−,−.+,−|NA|+,+,+,+|NA|NA|+,+,NA,NA|−,−,−|NA|−,−,+,−|NA|NA|+,+,+,+,+
|Neurologic
|Developmental delay|+|+|+|+,+,+,+|+,−|NA|+|+|+,+,+,−|+,NA,NA,+|NA|+|+,NA,NA,NA,NA,+|+,+,+,+|+,+,+|+,+|+,+,+,+|+,+,+,+|+|+,+,+,+,+
|Intellectual disability|+|n.e.|n.e.|+,+,+,+|+,−|+,+,+,+,+,+|+|−|S.,Mi.,S.,Borderline|Mo.,Mo.,Mo.,S.|+,+,+,+|+|+,Mo.,Mo.,Mo.,Mo.,S.|+,+,+,+|+,+,+|+,+|Mo.,Mo.,S.,S.|+,+,+,NA|+|+,+,+,+,+
|Speech delay|+|+|+|+,+,+,+|+,−|NA|+|+|+,+,Speech less,−|+, NA,NA,+|NA|+|+,NA,NA,NA,NA,+|+,+,+,NA|+,+,NA|+,+|+,+,+,+|+,+,+,NA|+|+,+,+,+,+
|Behavioral Disorder|+|+|−|+,+,+,+|+,+|NA|+|+|+,+,+,−|+,NA,NA,NA|NA|NA|NA|NA|+,NA,NA|NA|−,−,+,+|NA,NA,+,NA|+|NA
|Hypotonia|+|+|+|+,+,NA|−,−|−,−,−,−,−,−|−|−|+,Mi.,+,−|+,NA,NA,NA|NA|+|−,NA,NA, NA,NA,NA|NA|NA|NA,+|NA,+,+,+|+,+,+,−|NA|+,+,+,+,+
|Seizures|+|+|+|−,−,−,−|+,−|−,−,−,−,−,−|+|−|+,+,−,−|+,+,+,+|−,+,+,−|−|−,−,−,−,−,+|+,−,+,+|−,NA,NA|NA,+|+,−,+,+|−,−,−,−|−|+,+,+,+,+
|Seizure Onset|Infancy|4.5 years|2 years|NA|21 months|NA|6 years|NA|Infancy|8 years, NA,NA,Infancy|‘Early’|NA|NA|NA|NA|Infancy|NA,Infancy|NA|NA|Infancy
|Ataxic gait|+|+|+|+,+|+,+|NA|+|−|+,+,+,−|Mi.,Mi.,−,NA|−,−,−,−|+|−,−,−,−,−,−|NA|−,NA,NA|NA,−|−,−,−,−|−,−,−,−|−|+,+,+,+,+
|Spasticity|−|−|+|+,−,−,−|NA|NA|−|−|NA|NA|NA|NA|−,−,−,−,−,+|+,−,NA,NA|NA|NA|−,−,−,+|NA,NA,NA,+|−|NA
|Cerebellar hypoplasia|+|+|−|−,−,NA|−,−|NA,NA,NA,−,NA|−|−|+,+,+,+|+,+,Mi.,+|−,+,+,−|+|+,+,+,+,+,+|NA|+,+,+|+,+,+|NA,+,NA,+|+,+,+,+|+|+,+,+,+,+
|Ventriculomegaly|+|+|−|−,−,NA|+,+|NA,NA,NA,+,NA|−|+|+,+,−,+|+,+,−,+|−,+,+,−|+|+,+,+,+,+,+|NA,NA,NA,−|+,+,+|+,+,+|NA,−,NA,+|+,+,+,+|+|+,+,+,+,+
- Al-Owain 2011 : 3 garçons avec légèe dysmorphie, *1 fille dysmorphique* (cf photo)
https://pubmed.ncbi.nlm.nih.gov/20528889/
prominent forehead, long flat facies, strabismus, large ears, long tubular nose, and prominent chin.
- Bergman 2003 : mère porteuse, strabisme seul
10.1093/brain/awg173
- des Portes 2004 : 4 hommes
10.1002/ajmg.a.20422
- Busa 2017 : 1 garçon
10.1097/MCD.0000000000000139
- chabrol 2005 : 7 garçons
10.1002/ajmg.a.30882