tag:blogger.com,1999:blog-2186593343917545414.post2186427902062254784..comments2024-03-10T12:29:30.004-07:00Comments on pediatric neurology: SPG 47Galen Breningstall, MDhttp://www.blogger.com/profile/07170864203251456228noreply@blogger.comBlogger3125tag:blogger.com,1999:blog-2186593343917545414.post-4906961157075405022016-12-14T10:48:09.852-08:002016-12-14T10:48:09.852-08:00Hereditary Spastic Paraplegia, type 47, otherwise ...Hereditary Spastic Paraplegia, type 47, otherwise known as "SPG47", is an ultra-rare neurodegenerative disease. Children afflicted with this genetic disorder generally present with symptoms including global developmental delay, microcephaly, seizures, malformation of the brain, and hypotonia (low-muscle tone). They often learn to walk between the ages of 2-2½. They tend to lose that ability a few months or a few years later as they develop hypertonia (high-muscle tone) and muscle spasticity. Of the 11 confirmed cases of SPG47 in the world at this time, the first 9 patients have progressed to loss of mobility in some or all extremities, and are severely intellectually challenged.<br /><br />Because of the extreme rarity of SPG47, very little research has been conducted to date, and there is no known cure. SPG47 is caused by a mutation in the AP4B1 gene. It is an autosomal recessive disease, which means that both parents have contributed a defective recessive gene to the child. The result is that the child is unable to correctly produce a protein which is required for functioning of the central motor neurons in the brain.<br /><br />The Cure SPG47 non-profit organization was founded in 2016 by families of two of the eleven known patients. We refuse to accept the bleak prognosis which our children face. We have decided to fight. The purpose of this organization is to study and seek a cure for SPG47. We aim to improve the quality of life for children impacted by SPG47 by accelerating the research for a cure or treatment and providing financial support for patient therapies critical to their well-being and rehabilitation.<br /><br />https://curespg47.org/Galen Breningstall, MDhttps://www.blogger.com/profile/07170864203251456228noreply@blogger.comtag:blogger.com,1999:blog-2186593343917545414.post-91255954427833217322016-12-14T10:27:56.184-08:002016-12-14T10:27:56.184-08:00What is spastic paraplegia (SPG47)?
Spastic parap...What is spastic paraplegia (SPG47)?<br /><br />Spastic paraplegia-47 (SPG47) is an extremely rare, newly recognized genetic disorder resembling cerebral palsy. It is part of a group of disorders known as hereditary spastic paraplegia (HSP) and is sometimes called “HSP type 47.”<br /><br />SPG47 is present at birth and causes severe, progressive spasticity and muscle weakness, especially in the lower limbs. In infancy, children with SPG47 have very low muscle tone (hypotonia). As they grow, they develop spasticity (tight, stiff muscles that make movement difficult), together with cognitive deficits.<br /><br />SPG47 is a recessive disorder caused by two copies of a mutation in a gene called AP4B1, one inherited from each parent. It is thought that these mutations affect the ability of cells in the nervous system to process proteins. Since very few cases have been reported to date, our understanding of the full effects of SPG47 is still emerging.<br /><br />SPG47 signs and symptoms<br /><br />Virtually all children with SPG47 have:<br /><br />A “floppy” appearance in infancy due to low muscle tone<br />Increasing spasticity and paralysis in the lower limbs starting in early childhood<br />Intellectual disability<br />Microcephaly (a smaller than normal head)<br />Delayed motor development<br />Poor or absent speech development<br /><br />Other known features of SPG47 can include the following (not every child will have these features):<br /><br />Short stature<br />Late walking and later loss of the ability to walk independently<br />Dystonia (involuntary muscle contractions)<br />Seizures<br />Facial differences that can include:<br />a high palate<br />a wide nasal bridge<br />a bulbous nose<br />a wide mouth<br />a protruding tongue<br />a short filtrum (the groove between the bottom of the nose and top of the lips)<br />a narrow forehead<br />Joint abnormalities, such as backwards bending of the knee or hip dysplasia (loose hip joint)<br />Flat feet or club feet<br /><br />My baby was born with SPG47. What can I expect as he gets older?<br /><br />Because of progressive leg spasticity, children with SPG47 often lose their ability to walk independently, requiring a walker or canes. Many become wheelchair-bound before their teens. Others can walk with a waddling gait. Some children known to have SPG47 have reached their early 20s, but long-term life expectancy for this condition is still unclear, as it was only first recognized in 2011. However, many children with hereditary spastic paraplegias in general have a normal life expectancy.<br /><br />How is SPG47 treated?<br /><br />There is unfortunately no specific treatment for SPG47. However, physical, occupational and speech therapies can help children develop and preserve motor and communication skills. Muscle relaxants and Botox injections can help relieve spasticity in the muscles, and physical therapy can increase strength and range of motion. At Boston Children’s Hospital, we care for patients with spastic paraplegia in the Neuromuscular Center, the Cerebral Palsy Program and the Clinical Genetics program.<br /><br />Are my other children at risk?<br /><br />Since SPG47 is a recessive disorder, the chances of you and your spouse having another affected child are 1 in 4. Genetic counseling is often helpful if you are planning to have more children.<br /><br />http://www.childrenshospital.org/conditions-and-treatments/conditions/spastic-paraplegia-47/overview<br />Galen Breningstall, MDhttps://www.blogger.com/profile/07170864203251456228noreply@blogger.comtag:blogger.com,1999:blog-2186593343917545414.post-16742235828952731492016-12-14T10:24:39.002-08:002016-12-14T10:24:39.002-08:00Abdollahpour H, Alawi M, Kortüm F, Beckstette M, S...Abdollahpour H, Alawi M, Kortüm F, Beckstette M, Seemanova E, Komárek V, Rosenberger G, Kutsche K. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome. Eur J Hum Genet. 2015 Feb;23(2):256-9.<br /><br />Abstract<br />The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome.Galen Breningstall, MDhttps://www.blogger.com/profile/07170864203251456228noreply@blogger.com