Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

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Idiopathic infantile nystagmus (IIN) consists of involuntary oscillations of the eyes. The familial form is most commonly X-linked. We recently found mutations in a novel gene FRMD7 (Xq26.2), which provided an opportunity to investigate a genetically defined and homogeneous group of patients with nystagmus. We compared clinical features and eye movement recordings of 90 subjects with mutation in the gene (FRMD7 group) to 48 subjects without mutations but with clinical IIN (non-FRMD7 group). Fifty-eight female obligate carriers of the mutation were also investigated. The median visual acuity (VA) was 0.2 logMAR (Snellen equivalent 6/9) in both groups and most patients had good stereopsis. The prevalence of strabismus was also similar (FRMD7: 7.8%, non-FRMD7: 10%). The presence of anomalous head posture (AHP) was significantly higher in the non-FRMD7 group (P < 0.0001). The amplitude of nystagmus was more strongly dependent on the direction of gaze in the FRMD7 group being lower at primary position (P < 0.0001), compared to non-FRMD7 group (P = 0.83). Pendular nystagmus waveforms were also more frequent in the FRMD7 group (P = 0.003). Fifty-three percent of the obligate female carriers of an FRMD7 mutation were clinically affected. The VA's in affected females were slightly better compared to affected males (P = 0.014). Subnormal optokinetic responses were found in a subgroup of obligate unaffected carriers, which may be interpreted as a sub-clinical manifestation. FRMD7 is a major cause of X-linked IIN. Most clinical and eye movement characteristics were similar in the FRMD7 group and non-FRMD7 group with most patients having good VA and stereopsis and low incidence of strabismus. Fewer patients in the FRMD7 group had AHPs, their amplitude of nystagmus being lower in primary position. Our findings are helpful in the clinical identification of IIN and genetic counselling of nystagmus patients.

Periodic alternating nystagmus consists of involuntary oscillations of the eyes with cyclical changes of nystagmus direction. It can occur during infancy (e.g. idiopathic infantile periodic alternating nystagmus) or later in life. Acquired forms are often associated with cerebellar dysfunction arising due to instability of the optokinetic-vestibular systems. Idiopathic infantile periodic alternating nystagmus can be familial or occur in isolation; however, very little is known about the clinical characteristics, genetic aetiology and neural substrates involved. Five loci (NYS1-5) have been identified for idiopathic infantile nystagmus; three are autosomal (NYS2, NYS3 and NYS4) and two are X-chromosomal (NYS1 and NYS5). We previously identified the FRMD7 gene on chromosome Xq26 (NYS1 locus); mutations of FRMD7 are causative of idiopathic infantile nystagmus influencing neuronal outgrowth and development. It is unclear whether the periodic alternating nystagmus phenotype is linked to NYS1, NYS5 (Xp11.4-p11.3) or a separate locus. From a cohort of 31 X-linked families and 14 singletons (70 patients) with idiopathic infantile nystagmus we identified 10 families and one singleton (21 patients) with periodic alternating nystagmus of which we describe clinical phenotype, genetic aetiology and neural substrates involved. Periodic alternating nystagmus was not detected clinically but only on eye movement recordings. The cycle duration varied from 90 to 280 s. Optokinetic reflex was not detectable horizontally. Mutations of the FRMD7 gene were found in all 10 families and the singleton (including three novel mutations). Periodic alternating nystagmus was predominantly associated with missense mutations within the FERM domain. There was significant sibship clustering of the phenotype although in some families not all affected members had periodic alternating nystagmus. In situ hybridization studies during mid-late human embryonic stages in normal tissue showed restricted FRMD7 expression in neuronal tissue with strong hybridization signals within the afferent arms of the vestibulo-ocular reflex consisting of the otic vesicle, cranial nerve VIII and vestibular ganglia. Similarly within the afferent arm of the optokinetic reflex we showed expression in the developing neural retina and ventricular zone of the optic stalk. Strong FRMD7 expression was seen in rhombomeres 1 to 4, which give rise to the cerebellum and the common integrator site for both these reflexes (vestibular nuclei). Based on the expression and phenotypic data, we hypothesize that periodic alternating nystagmus arises from instability of the optokinetic-vestibular systems. This study shows for the first time that mutations in FRMD7 can cause idiopathic infantile periodic alternating nystagmus and may affect neuronal circuits that have been implicated in acquired forms.

Our study supports the findings of inefficiencies in set-shifting after full recovery from AN. Higher perfectionism in the recAN group is associated with better set-shifting ability, whereas higher perfectionism in the healthy control group is related to worse set-shifting ability.

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This study does not support results from other studies showing that rec AN participants perform better in decision-making. Results from this study show that planning is impaired even after full recovery from AN.

BackgroundTo study the longer term effects of an internet-based CBT intervention for relapse prevention (RP) in anorexia nervosa.Methods210 women randomized to the RP intervention group (full and partial completers) or the control group were assessed for eating and general psychopathology. Multiple regression analysis identified predictors of favorable course concerning Body Mass Index (BMI). Logistic regression analysis identified predictors of adherence to the RP program.ResultsMost variables assessed showed more improvement for the RP than for the control group. However, only some scales reached statistical significance (bulimic behavior and menstrual function, assessed by expert interviewers blind to treatment condition). Very good results (BMI) were seen for the subgroup of “full completers” who participated in all nine monthly RP internet-based intervention sessions. “Partial completers” and controls (the latter non-significantly) underwent more weeks of inpatient treatment during the study period than “full completers”, indicating better health and less need for additional treatment among the “full completers”. Main long-term predictors for favorable course were adherence to RP, more spontaneity, and more ineffectiveness. Main predictors of good adherence to RP were remission from lifetime mood and lifetime anxiety disorder, a shorter duration of eating disorder, and additional inpatient treatment during RP.ConclusionsConsidering the high chronicity of AN, internet-based relapse prevention following intensive treatment appears to be promising.