Symptoma

Autosomal Recessive Spastic Paraplegia Type 52

Severe Mental Impairment with Progressive Spastic Paraplegia

Neuromuscular syndromes are presented clinically either as a case study or as an overview from the literature, accompanied by text presenting molecular defects, and differential diagnosis. [books.google.com]

Acronym SPG52 Synonyms Cerebral palsy, spastic quadriplegic 6 CPSQ6 Keywords Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. [uniprot.org]

Clinical characteristics are presented in table 1. Neuropsychological tests revealed deficits of auditory short-term memory and visuomotor coordination. Table 1. Clinical characteristic of affected family members. [mdsabstracts.org]

Presentation on theme: "Spinal chord. [slideplayer.com]

Muscle weakness when present is seen in iliopsoas, tibialis anterior and, to a lesser extent, the hamstrings. [jnnp.bmj.com]

  • Short Stature

    Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). [ncbi.nlm.nih.gov]

    SPASTIC PARAPLEGIA 45, AUTOSOMAL RECESSIVE; SPG45 Is also known as ;autosomal recessive spastic paraplegia type 65; spg45; spg65 Related symptoms: Autosomal recessive inheritance Intellectual disability Global developmental delay Short stature Microcephaly [mendelian.co]

    Category Subcategory Feature Growth Height Short stature Head And Neck Head Microcephaly [ EoM Image ] Further information: Morphology of elements Mouth High-arched palate Full lips Wide mouth [ EoM Image ] Further information: Morphology of elements [mnglabs.com]

    Adaptor protein complex 4 deficiency causes severe autosomal-recessive intellectual disability, progressive spastic paraplegia, shy character, and short stature. Am. J. Hum. Genet. 2011; 88(6):788-95. doi: 10.1016/j.ajhg.2011.04.019. [invitae.com]

    Slavotinek AM, Pike M and Mills K (1996) Cataracts, motor system disorder, short stature, learning difficulties, and skeletal abnormalities: a new syndrome? American Journal of Human Genetics 62: 42–47. [els.net]

  • Wheelchair Bound

    The majority of children become non-ambulatory and usually wheelchair bound. Over time spasticity progresses to involve the upper extremities, resulting in a spastic tetraplegia. [ncbi.nlm.nih.gov]

    Thereafter, his ataxic gait progressed slowly, and he became wheelchair bound at age 52. At his latest visit at age 74, his mini-mental state examination score was 30. He had no optic nerve atrophy, ophthalmoplegia, nystagmus or blepharoptosis. [nature.com]

    She became wheelchair bound from the age of 43 years. Examination at the age of 63 years showed severe cerebellar ataxia in truncus and extremities. [journals.plos.org]

    A characteristic feature of HSP, which has been stressed by several authors, is the marked discrepancy between the often severe spasticity and only mild or absent muscle weakness. 8 14 This is demonstrated by the patient with HSP who is wheelchair bound [jnnp.bmj.com]

  • Developmental Delay

    All have global developmental delay. Speech development is significantly impaired and many affected individuals remain nonverbal. Intellectual disability in older children is usually moderate to severe. [ncbi.nlm.nih.gov]

    Postnatal features include severe developmental delay, congenital cataracts (in some), and marked UV sensitivity of the skin. Survival beyond 6 years of age is rare. [mendelian.co]

    Recessive loss-of-function mutations in AP4S1 cause mild fever-sensitive seizures, developmental delay and spastic paraplegia through loss of AP-4 complex assembly. Hum. Mol. Genet. 2015; 24(8):2218-27. doi: 10.1093/hmg/ddu740. [invitae.com]

    delay with de novo double mutations in NF1 and MAGEL2)(英語)(会議録/症例報告) Author： Akamine Satoshi (Department of Pediatrics, University of Kyushu), Sagata Noriaki, Sakai Yasunari, Kato Takahiro, Matsushita Yuki, Sanefuji Masafumi, Ishizaki Yoshito, Torisu [demo.jamas.or.jp]

  • Coarse Facial Features

    facial features Eyes Hypertelorism [ EoM Image ] Further information: Morphology of elements Nose Prominent nose [ EoM Image ] Further information: Morphology of elements Bulbous nose [ EoM Image ] Further information: Morphology of elements Broad nasal [mnglabs.com]

    Coarse facial features MedGen UID: 335284 • Concept ID: C1845847 • Finding Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous [ncbi.nlm.nih.gov]

  • Delayed Speech Development

    All have global developmental delay. Speech development is significantly impaired and many affected individuals remain nonverbal. Intellectual disability in older children is usually moderate to severe. [ncbi.nlm.nih.gov]

  • High Arched Palate

    Category Subcategory Feature Growth Height Short stature Head And Neck Head Microcephaly [ EoM Image ] Further information: Morphology of elements Mouth High-arched palate Full lips Wide mouth [ EoM Image ] Further information: Morphology of elements [mnglabs.com]

  • Foot Deformity

    Associated complications include dysphagia, contractures, foot deformities, dysregulation of bladder and bowel function, and a pseudobulbar affect. About 50% of affected individuals have seizures. [ncbi.nlm.nih.gov]

    Kyphoscoliosis, macrocephaly, and various foot deformities have been described. CT scans of the brain may show generalized cerebral atrophy and a hypoplastic corpus callosum. [disorders.eyes.arizona.edu]

    The primary spino-cerebellar atrophies and their associated defects, with a study of the foot deformity. Brain, 84, 289 – 300. Wadia, H. and Swami, R.K. ( 1971 ). A new form of heredo-familial spinocerebellar degeneration with slow eye movements. [cambridge.org]

  • Flexion Contracture

    Flexion contracture MedGen UID: 3227 • Concept ID: C0009917 • Anatomical Abnormality A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. [ncbi.nlm.nih.gov]

  • Bulbous Nose

    nose [ EoM Image ] Further information: Morphology of elements Broad nasal bridge [ EoM Image ] Further information: Morphology of elements Inheritance - Autosomal recessive Miscellaneous - Two unrelated families have been reported (last curated May [mnglabs.com]

    Bulbous nose MedGen UID: 66013 • Concept ID: C0240543 • Finding Increased volume and globular shape of the anteroinferior aspect of the nose. [ncbi.nlm.nih.gov]

  • Hypertelorism

    Hypertelorism MedGen UID: 9373 • Concept ID: C0020534 • Finding Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. [ncbi.nlm.nih.gov]

    Morphology of elements Mouth High-arched palate Full lips Wide mouth [ EoM Image ] Further information: Morphology of elements Face Facial hypotonia Short philtrum [ EoM Image ] Further information: Morphology of elements Coarse facial features Eyes Hypertelorism [mnglabs.com]

  • Hyperreflexia

    Spasticity is usually accompanied by HYPERREFLEXIA and variable degrees of MUSCLE WEAKNESS. [ncbi.nlm.nih.gov]

    […] mass Neurologic Central Nervous System Febrile seizures (in some patients) Focal seizures (in some patients) Spasticity Thin or absent corpus callosum (in some patients) Mental retardation, severe Delayed psychomotor development Loss of ability to walk Hyperreflexia [mnglabs.com]

    […] about how to achieve it with Mendelian Learn more Other signs and symptoms that you may find interesting Arthritis and B-cell lymphoma, related diseases and genetic alterations Rod-cone dystrophy and Omphalocele, related diseases and genetic alterations Hyperreflexia [mendelian.co]

    […] spasticity is increased at the hamstrings, quadriceps and ankles  Weakness is most notable at the iliopsoas, tibialis anterior, hamstring muscles  difficulty in walking, decreased vibratory sense at the ankles, and paresthesia  In lower extremities hyperreflexia [slideshare.net]

    Examination at the age of 22 years after a traffic accident revealed failure of abduction of the left eye, hyperreflexia in all four extremities and Babinski sign. [journals.plos.org]

  • Babinski Sign

    Principles of Neurology, 6th ed, p54) Babinski sign MedGen UID: 19708 • Concept ID: C0034935 • Finding A reflex characterized by upward movement of the great toe and an outward movement of the rest of the toes, when the sole of the foot is stroked. [ncbi.nlm.nih.gov]

    Neurological examination at age 52 showed ataxic dysarthria, exaggerated patellar and Achilles tendon reflexes without Babinski signs and lower limb ataxia. His gait was wide-based and staggering. [nature.com]

    […] years) Disease duration (years) SARA (0-40) MAS (lower limbs) SPRS (0-52) ENG (sensorimotor neuropathy) 1 47 1,5 45 23,5 1,5 30 2 45 4 41 20 1 21 3 33 2 31 15 1 19 4 30 5 25 16 1,5 23 Nr yellow streaks of the retina Nystagmus Knee reflex Achilles reflex Babinski [mdsabstracts.org]

    sign Motor delay Athetosis Intellectual disability, severe Growth delay Hypoplasia of the corpus callosum Cerebellar hypoplasia Rare Symptoms - Less than 30% cases Proptosis Profound global developmental delay Generalized myoclonic seizures Encephalocele [mendelian.co]

    Examination at the age of 22 years after a traffic accident revealed failure of abduction of the left eye, hyperreflexia in all four extremities and Babinski sign. [journals.plos.org]

  • Poor or Absent Speech

    SPG52 is characterized by neonatal hypotonia that progresses to hypertonia and spasticity, and severe mental retardation with poor or absent speech development. Some patients may have seizures. [uniprot.org]

    [from GeneReviews ] From OMIM Spastic quadriplegia-52 is an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development [ncbi.nlm.nih.gov]

    Top matches: Medium match LISSENCEPHALY 8; LIS8 Lissencephaly-8 is an autosomal recessive neurologic disorder characterized by delayed psychomotor development, intellectual disability with poor or absent speech, early-onset refractory seizures, and hypotonia [mendelian.co]

  • Febrile Seizures

    seizures (in some patients) Focal seizures (in some patients) Spasticity Thin or absent corpus callosum (in some patients) Mental retardation, severe Delayed psychomotor development Loss of ability to walk Hyperreflexia Extensor plantar responses Lack [mnglabs.com]

    Febrile seizures MedGen UID: 3232 • Concept ID: C0009952 • Disease or Syndrome A seizure occurring in infants and young children that occurs in the setting of fever. [ncbi.nlm.nih.gov]

    The family reported by Hardies and collaborators consisted of two affected sisters with simple febrile seizures starting in infancy and subsequent easily treatable focal seizures. [epilepsygenetics.net]

  • Neonatal Hypotonia

    SPG52 is characterized by neonatal hypotonia that progresses to hypertonia and spasticity, and severe mental retardation with poor or absent speech development. Some patients may have seizures. [uniprot.org]

    [from GeneReviews ] From OMIM Spastic quadriplegia-52 is an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development [ncbi.nlm.nih.gov]

It is divided into the following sections: Overview Differential Diagnoses & Workup Treatment & Medication Follow-up Multimedia [hspersunite.org.au]

Our findings confirm that this is indeed not an uncommon presentation of this disorder and we suggest that SPG7 gene analysis should be included in the diagnostic workup of autosomal recessive PEO, especially if spasticity is present. [journals.plos.org]

It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. Our staff consists of biologists and biochemists that are not trained to give medical advice . [uniprot.org]

Key points for each genetic disease are identified to suggest treatment, when available, or the main clinical exams useful in follow-up of patients. [books.google.com]

37 Treatment Physical therapy Nerve and muscle trophic drugs Treatment of complications Treatment of heart disorders 38 Lateral Amiotrophic Sclerosis 39 Lateral Amiotrophic Sclerosis (ALS) Degenerative disease of the central nervous system Degeneration [slideplayer.com]

Treatment Treatment Options: No treatment has been reported for this condition but physical therapy and assistive devices such as hearing and visual aids may be helpful. References Article Title: DDD study. [disorders.eyes.arizona.edu]

There are no specific treatments to prevent HSP. Management consists of symptomatic treatment and regular physical therapy to strengthen muscles. [cags.org.ae]

PMID: 16672289 Prognosis Pearce DA Hum Genet 1999 Jun;104(6):443-8. [ncbi.nlm.nih.gov]

Prognosis [ edit ] Although HSP is a progressive condition, the prognosis for individuals with HSP varies greatly. It primarily affects the legs although there can be some upperbody involvement in some individuals. [en.wikipedia.org]

Classifying HSP as uncomplicated or complicated is also important for prognosis. Families with “uncomplicated” HSP (e.g., HSP caused by SPG4 /spastin gene mutation) are not at risk of having offspring with “complicated” HSP. [neupsykey.com]

This distinction is important for genetic counseling of family members and for the patient’s prognosis, in that HSP generally carries a more favorable prognosis. [2] Other components of the differential diagnosis of HSP are similar to those of PLS. [emedicine.medscape.com]

Disorders, the prognosis of which differs significantly from HSP, such as multiple sclerosis and familial motor neuron disease should also be excluded. The necessity for investigations will vary depending on the individual clinical picture. [jnnp.bmj.com]

PMID: 15037681 Etiology J Neurol Sci 2014 Dec 15;347(1-2):368-71. Epub 2014 Oct 16 doi: 10.1016/j.jns.2014.10.017. PMID: 25454648 Aulitzky A, Friedrich K, Gläser D, Gastl R, Kubisch C, Ludolph AC, Volk AE J Neurol Sci 2014 Dec 15;347(1-2):352-5. [ncbi.nlm.nih.gov]

Risch N et al. (1999) A genomic screen of autism: evidence for a multilocus etiology. [ ] 26. [moldiag.com]

Primary lateral sclerosis The etiology of primary lateral sclerosis (PLS) is unknown, but it may be similar to that proposed for ALS. [emedicine.medscape.com]

Etiological heterogeneity in X-linked spastic paraplegia. Am J Hum Genet 1987 ; 41 : 933 –43 Goldblatt J, Ballo R, Sachs B, et al. X-linked spastic paraplegia: evidence for homogeneity with a variable phenotype. [ajnr.org]

Through the past 15 years, significant progress has been made in improving our understanding of the genetic etiology of the ARCA. [wjgnet.com]

Consequently, they are often approached together in epidemiological studies. [karger.com]

Jorde LB et al. (1990) The UCLA-University of Utah epidemiologic survey of autism: genealogical analysis of familial aggregation. [ ] 6. Abramson RK et al. (1989) Elevated blood serotonin in autistic probands and their first-degree relatives. [ ] 7. [moldiag.com]

Molecular epidemiology and clinical spectrum of hereditary spastic paraplegia in the Japanese population based on comprehensive mutational analyses. J Hum Genet 2014; 59 : 163–172. [nature.com]

Epidemiology The prevalence of HSP varies in different studies. Such variation is probably due to a combination of differing diagnostic criteria, variable epidemiological methodology, and geographical factors. [jnnp.bmj.com]

The majority of individuals with HSP have a normal life expectancy. [16] Epidemiology [ edit ] Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people. [34] A Norwegian study of more than 2.5 [en.wikipedia.org]

J Clin Endocrinol Metab 93:2084–2088 CrossRef PubMed Google Scholar Werner ER, Blau N, Thöny B (2011) Tetrahydrobiopterin: biochemistry and pathophysiology (review). [link.springer.com]

Pathophysiology [ edit ] The major feature of HSP is a length dependent axonal degeneration. [21] These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. [en.wikipedia.org]

Koenig[ 10 ] proposed a classification of ARCA based on topographical and pathophysiological criteria, while in the next year the group of Filla proposed a pathogenic classification of the hereditary ataxias[ 11 ]. [wjgnet.com]

This is the first step towards the identification of a new gene crucial for understanding the underlying pathophysiology of HSP. [academic.oup.com]

Pathophysiological insights into ALS with C9ORF72 expansions. Journal of Neurology, Neurosurgery and Psychiatry, 84(8), 931-935. [sydney.edu.au]

Treatment No specific treatment is known that would prevent, slow, or reverse HSP Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being 26. Gen. Spas ticity Oral Agents Foc. [slideshare.net]

There are no specific treatments to prevent HSP. Management consists of symptomatic treatment and regular physical therapy to strengthen muscles. [cags.org.ae]

It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints. [ncbi.nlm.nih.gov]

Treatment [ edit ] No specific treatment is known that would prevent, slow, or reverse HSP. Available therapies mainly consist of symptomatic medical management and promoting physical and emotional well-being. [en.wikipedia.org]

The long nerves (axons) are prevented from doing their critical job of sending the right signals to control the muscles. HSP is classified as an upper motor neurone neurodegenerative disease. [hspersunite.org.au]