De Novo Occurrence of Novel SPG3A/Atlastin Mutation Presenting as Cerebral Palsy

Rainier, Shirley; Sher, Carron; Reish, Orit; Thomas, Dave; Fink, John K.

doi:10.1001/archneur.63.3.445

Cited by 61 publications

(35 citation statements)

References 5 publications

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“…2 Childhoodonset HSP needs to be differentiated from more common conditions like cerebral palsy and other mimicking neurodegenerative disorders that particularly affect the white matter of the brain. 3 HSP is classified as either pure or complicated based on well-established criteria. 4,5 The disease is mainly reported in adults and there have been only a few studies in children.…”

Section: H Ereditary Spastic Paraplegia (Hsp)mentioning

confidence: 99%

Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A Study of 74 Cases = الطيف السريري للشلل السفلي التشنجي الوراثي في الأطفال : دراسة 74 حالة

Koul¹,

Al-Murshedi²,

Al-Azri³

et al. 2013

SQUMJ

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abstract:Objectives: The aim of the study was to explore the spectrum of hereditary spastic paraplegia (HSP) in children in Oman. Methods: This retrospective study was carried out between January 1994 and August 2011 on children with delayed development, gait disorders and motor handicaps, with signs of symmetrical pyramidal tract involvement. A detailed perinatal and family history, including the age of onset of symptoms, was recorded. The children were labelled as having either the pure or complicated form of HSP based on the established diagnostic criteria. In families with more than one affected child, parents and all other siblings were also examined. Results: Within the study, 74 children from 31 families were diagnosed with HSP. Parental consanguinity was seen in 91% of cases, with 44 children (59.4%) experiencing onset of the disease under one year of age. Complicated HSP was the most common type, seen in 81.1%. Speech involvement, mental retardation, and epilepsy were the most common associated abnormalities. Nonspecific white matter changes and corpus callosum abnormalities were noted in 24.3% of cases on magnetic resonance imaging. Conclusion: The study described clinical features of 74 children with HSP. Autosomal recessive complicated HSP was seen in 81.1% of cases. Keywords

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Section: H Ereditary Spastic Paraplegia (Hsp)mentioning

confidence: 99%

Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A Study of 74 Cases = الطيف السريري للشلل السفلي التشنجي الوراثي في الأطفال : دراسة 74 حالة

Koul¹,

Al-Murshedi²,

Al-Azri³

et al. 2013

SQUMJ

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“…3 If these investigations are negative, ATL1 and SPAST mutation analysis should be considered because sporadic cases (due to de novo mutations and incomplete penetrance) have been described in these HSP forms. 4,5 When confronted with a child with a complicated spastic paraplegia, the accompanying signs and symptoms will lead to a differential diagnosis and the required specific diagnostic evaluation ( …”

Section: Genetic Testing In Childrenmentioning

confidence: 99%

“…Many patients with childhood-onset HSP are mistakenly diagnosed with cerebral palsy. 4,5 In children with spastic paraplegia in whom no acquired cause can be identified, HSP should be considered. A positive family history aids with the diagnosis.…”

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confidence: 99%

Child Neurology: Hereditary spastic paraplegia in children

Bot¹,

Warrenburg²,

Kremer³

et al. 2010

Neurology

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Because the medical literature on hereditary spastic paraplegia (HSP) is dominated by descriptions of adult case series, there is less emphasis on the genetic evaluation in suspected pediatric cases of HSP. The differential diagnosis of progressive spastic paraplegia strongly depends on the age at onset, as well as the accompanying clinical features, possible abnormalities on MRI, and family history. In order to develop a rational diagnostic strategy for pediatric HSP cases, we performed a literature search focusing on presenting signs and symptoms, age at onset, and genotype. We present a case of a young boy with a REEP1 (SPG31) mutation.CASE REPORT A 4-year-old boy presented with progressive walking difficulties from the time he started walking at the age of 12 to 13 months. His family history was significant for minimal gait abnormalities with onset after age 35, occurring in the patient's mother, maternal grandfather, and maternal aunt; none of them had ever sought medical attention. Neurologic examination revealed a mildly spastic gait and marked lower limb hyperreflexia with bilateral Babinski signs present. Vibration perception was reduced at the ankles. Neurologic examination of the patient's mother and maternal aunt revealed subtle gait abnormalities with bilateral Babinski signs present.MRI of the brain and spinal cord and general metabolic screening revealed no abnormalities. Diagnostic genetic testing in both the patient and his mother revealed a pathogenic mutation (c.417 ϩ 1 GϾT) in REEP1 (SPG31) which causes a pure HSP. Mutations in ATL1 (SPG3A) and SPAST (SPG4) had previously been excluded. DISCUSSION HSP is a genetically and clinically heterogeneous group of disorders in which the main clinical feature is progressive lower limb spasticity secondary to pyramidal tract dysfunction. HSP is classified as pure if neurologic signs are limited to the lower limbs (although urinary urgency and mild impairment of vibration perception in the distal lower extremities may occur). In contrast, complicated forms of HSP display additional neurologic and MRI abnormalities such as ataxia, more significant peripheral neuropathy, mental retardation, or a thin corpus callosum. HSP may be inherited as an autosomal dominant, autosomal recessive, or X-linked disease. Over 40 loci and nearly 20 genes have already been identified.1 Autosomal dominant transmission is observed in 70% to 80% of all cases and typically results in pure HSP. Spastic paraplegia is a common problem in the daily practice of pediatric neurologists, generally caused by acquired brain disorders such as perinatal asphyxia or infections early in life resulting in cerebral palsy. In addition, there is a long list of more rare disorders to consider when confronted with spastic paraplegia including structural, infectious, demyelinating, and metabolic disorders (table). 3 Only in a small minority of cases does HSP underlie the spastic syndrome. Many patients with childhood-onset HSP are mistakenly diagnosed with cerebral palsy. 4,5 In children with spasti...

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“…6 Mutations in SPG3A gene encoding for atalastin protein are the most common cause of early childhood-onset autosomal dominant HSP, which is relatively non progressive and presents with spastic diplegia. 7,8 Treatment for HSP is exclusively symptomatic with physical therapy. 6 …”

Section: Myelopathiesmentioning

confidence: 99%