Mutations in the m-AAA proteases AFG3L2 and SPG7 are causing isolated dominant optic atrophy.

OBJECTIVE: To improve the genetic diagnosis of dominant optic atrophy (DOA), the most frequently inherited optic nerve disease, and infer genotype-phenotype correlations. METHODS: Exonic sequences of 22 genes were screened by new-generation sequencing in patients with DOA who were investigated for ophthalmology, neurology, and brain MRI. RESULTS: We identified 7 and 8 new heterozygous pathogenic variants in SPG7 and AFG3L2. Both genes encode for mitochondrial matricial AAA (m-AAA) proteases, initially involved in recessive hereditary spastic paraplegia type 7 (HSP7) and dominant spinocerebellar ataxia 28 (SCA28), respectively. Notably, variants in AFG3L2 that result in DOA are located in different domains to those reported in SCA28, which likely explains the lack of clinical overlap between these 2 phenotypic manifestations. In comparison, the SPG7 variants identified in DOA are interspersed among those responsible for HSP7 in which optic neuropathy has previously been reported. CONCLUSIONS: Our results position SPG7 and AFG3L2 as candidate genes to be screened in DOA and indicate that regulation of mitochondrial protein homeostasis and maturation by m-AAA proteases are crucial for the maintenance of optic nerve physiology

Accidental and nonaccidental head injuries in infants: a prospective study.

International audienceOBJECT: Head injury is a major cause of morbidity and death in infants, and child abuse is among its chief causes. Retinal hemorrhages (RHs) are of paramount importance for the diagnosis of child abuse; however, their sensitivity and specificity are poorly estimated. Subdural hematoma (SDH) is a common feature; however, its incidence and causative factors are poorly documented. METHODS: To study the epidemiology of head injuries in infants, factors predisposing to SDH, value of RH for the diagnosis of child abuse, and prognostic factors, the authors prospectively collected data from cases of head injury in infants who were hospitalized at their institution over a 3-year period. One hundred fifty cases were collected, 57 of which were due to child abuse. This prospective study allows the comparison of clinical, radiological, and ophthalmological features in accidental and nonaccidental trauma in infants. CONCLUSIONS: Subdural hematomas were significantly correlated with RH and with child abuse but not with idiopathic macrocranium. The sensitivity and specificity of RH for the diagnosis of child abuse were 75 and 93.2%, respectively. Retinal hemorrhages associated with accidental trauma were always mild, and the specificity of more severe RH for the diagnosis of child abuse was 100%. The grading of RH requires the expertise of a trained neuroophthalmologist. Child abuse was also significantly associated with antecedents of perinatal illness, absence of signs of impact, and seizures on presentation. Although child abuse represented just 38% of traumas, it was the cause of 71% of deaths and 90% of severe disability in this series. Abuse and the clinical severity on presentation were two significant and independent factors conditioning outcome

Traumatisme crânien du nourrisson

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

[Accidental or non-accidental brain injury in infants. Prospective study of 88 cases]

International audienceOBJECTIVE: To study the epidemiology of head injury (HI) in infants, the factors favouring the occurrence of a subdural haematoma (SDH), the prevalence of retinal haemorrhages (RH) and the prognostic factors, by comparing the non-accidental (NAHI) and accidental (AHI) head injuries. RH, in particular, are of fundamental value in the diagnosis of NAHI but, in the absence of systematic studies, their sensitivity and specificity for the diagnosis of the NAHI have rarely been assessed. METHOD: We prospectively collected the clinical, ophthalmologic and radiological data of HI occurring in children under 24 months old, notably by distinguishing essential macrocrania and symptomatic macrocrania of an SDH, by classifying the HI according to its severity. RESULTS: We observed 88 cases over a period of 22 months. It 28 cases it was NAHI and in the 60 others, AHI. The SDH was often correlated with the presence of retinal haemorrhages and the absence of signs of cranial impact, but not with child abuse or with essential macrocrania. The RH were of great importance in the diagnosis of NAHI; however, non-severe RH was noted in 4 cases of AHI. The neurological prognosis was essentially correlated with the initial clinical severity. CONCLUSION: Although only representing 33% of cases, child abuse was responsible for 2/3 of the deaths and for the totality of the severe morbidity in our series. The infants exhibiting perinatal problems represented an important group at risk of abuse, which justified their regular medical-social follow-up

Infantile traumatic subdural hematomas: outcome after five years.

International audienceOBJECTIVE: Although subdural hematomas (SDH) are common in infants, their long-term outcome is poorly documented in the literature. METHODS: Infants operated for SDH were followed prospectively and evaluated during their sixth year with systematic neurological evaluation and standard neuropsychological testing. RESULTS: We studied 48 infants operated for SDH. At the last checkup, 39 were normal, 5 had mild deficits, 3 had severe deficits and 1 was in a vegetative state. IQ measurements did not differ significantly from normal values, but did not accurately reflect the outcome. The only independent factor significantly affecting the final outcome was initial clinical severity. Age at surgery, surgical complications and the nature of the trauma (inflicted or accidental) did not independently influence the outcome. CONCLUSION: Long-term follow-up is required after treatment of SDH, to evaluate the child's changing needs in terms of medical and educational care

Resolution of acute acquired comitant esotropia after suboccipital decompression for Chiari I malformation.

International audiencePURPOSE: To report a case of acute comitant esotropia successfully treated with suboccipital decompression in a 9-year-old male patient with Chiari I malformation. DESIGN: Interventional case report. METHODS: A 9-year-old male with Chiari I malformation had acute onset of diplopia, headache, and comitant esotropia. RESULTS: About 9 months after suboccipital decompression, diplopia resolved and there was near orthophoria on examination 15 months after surgery. CONCLUSION: In view of our case and after a review of literature, we advocate primary suboccipital decompression to treat acute comitant esotropia in patients with Chiari I malformation. A follow-up period of at least 1 year rather than 6 months seems necessary to assess surgery effects