## Moortag 2018
Since 1998, OPHN1 mutations have been identified in 49 male and 14 female patie
Dysmorphic
features are often described in individuals with OPHN1 mutation, consisting of a long face
with deep-set eyes and marked infra-orbital creases, a long nose and a prominent chin [16, 18,
23]. However, these characteristics cannot be related to a specifically recognizable clinical
entity as it has been initially suggested, and absence of dysmorphism was previously reported
[1, 17, 20, 27, 30, 31]. In our cohort, the more severely affected patients (family A) presented
some of these reported facial features but affected individuals from family C, and family D
did not (Fig. 2).
Carrier females are usually described as asymptomatic, which could be attributed to protective skewed
inactivation of their affected X chromosome. This hypothesis is strengthened by the fact that a
random pattern of X chromosome inactivation is observed in most of the affected female
patients, usually with mild ID as in our cohort [23, 26, 28, 30], but occasionally with severe
symptoms [16] (Table 1). The large phenotypic variability in females might reflect that the
inactivation patterns measured in the peripheral blood may not be representative for other
tissues, in particular for the brain.
Moreover, it is now well-known that about 10% of X-
linked genes show variable patterns of inactivation and are expressed to different extents from
some inactive X chromosomes [33]. Interestingly, we noted that 1 out of 14 previously
reported female patients with a severe phenotype, including moderate to severe ID,
dysmorphic features and cerebellar signs, showed an extremely skewed X-inactivation pattern
[28]. We could hypothesize that this severely affected female expressed her X mutated allele.
However, expression studies to identify the inactive X chromosome were lacking in this
publication [28]
## Tentler 1999 2 soeurs, sans dysmorphie rapportée
https://www.nature.com/articles/5200320.pdf
## Autres
- Bergman 2003 : mère porteuse saine, strabisme seul