Infantile neuroaxonal dystrophy and pla2g6associated neurodegeneration. The patient was a boy with negative family history who showed progressive neurologic symptoms deviation of bulbi, muscle hypotonia and quadruplegia in flexion soon after. Infantile neuroaxonal dystrophy inad is a rare neurodegenerative disease that often cuts short the life span of a child to 10 years. Mim256600 a rare, familial disorder of early childhood manifested as progressive psychomotor deterioration, increased reflexes, positive babinski sign, hypotonia, and progressive blindness. Infantile neuroaxonal dystrophy inad is a rare autosomal recessive neurodegenerative disorder. A babys motor development will start out normally and then begin to slow down. Infantile neuroaxonal dystrophy is a rare pervasive developmental disorder that primarily affects the nervous system. Osteopetrosis and infantile neuroaxonal dystrophy genetic. Infantile neuroaxonal dystrophy an overview sciencedirect. Report pla2g6 mutation underlies infantile neuroaxonal dystrophy. Infantile neuroaxonal dystrophy inad is a rare neurodegenerative disease. Clinical heterogeneity of pla2g6 related parkinsonism. Targetednext generation sequencing using a custom neurology panel, containing 758 omimlisted genes.
Dec 10, 2018 infantile neuroaxonal dystrophy inad is a rare neurodegenerative disease that often cuts short the life span of a child to 10 years. Magnetic resonance imaging findings of hallervordenspatz syndrome and infantile neuroaxonal dystrophy are similar, suggesting that these two disease entities overlap. In order for a child to develop the disorder, each parent must pass on one copy of the mutated gene that causes the condition. Infantile neuroaxonal dystrophy genetics home reference nih. Infantile neuroaxonal dystrophy great ormond street hospital. Infantile neuroaxonal dystrophy brain oxford academic. Infantile neuroaxonal dystrophy definition of infantile. Before the identification of associated mutations in pla2g6. The authors excluded linkage in one consanguineous inad family by. A 36yearsold pregnant woman presented for obstetric follow up. Infantile neuroaxonal dystrophy genetic and rare diseases. Infantile neuroaxonal dystrophy inad is a rare autosomal recessive neurodegenerative disorder with. Two boys aged 3 years and 4 years and 2 months respectively, were admitted to the hospital due to delayed mental and motor development.
Neuroaxonal dystrophy is a rare progressive disorder of childhood characterized by mental deterioration and seizures. Pathologically, eosinophilic spheroids of swollen axoplasm are found in various central nervous system nuclei. Infantile neuroaxonal dystrophy is a type of lipid storage disorder that. Neuropathological and biochemical studies were done of a 912yearold girl with a sporadic form of infantile neuroaxonal dystrophy inad. Infantile neuroaxonal dystrophy hope for katherine belle. Novel pla2g6 mutations associated with an exonic deletion due. The classic form is usually diagnosed in infancy or early childhood and leads to a progressive loss of vision and developmental milestones. Sep 14, 2004 common clinical, radiologic, and pathologic features in infantile neuroaxonal dystrophy inad and pantothenate kinaseassociated neurodegeneration pkan have led to the hypothesis of an allelic relationship. Infantile neuroaxonal dystrophy inad condition and symptoms. Prenatal diagnosis of infantile neuroaxonal dystrophy. Catalytic function of pla2g6 is impaired by mutations.
One of the five families we studied did not link to pla2g6 locus, and in the family one of the two affected. Six patients aged 19 months to 9 years with proved neuroaxonal dystrophy one with the infantile form, five juvenile. The most typical neuropathological finding of this disease is axonal swelling. Background infantile neuroaxonal dystrophy inad is a recessive disease that results in total neurological degeneration and death in childhood. Infantile neuroaxonal dystrophy inad is a rare, inherited neurological disorder.
Infantile neuroaxonal dystrophy inad is a rare inherited disorder affecting the nerve axons which are responsible for conducting messages in the brain and other parts of the body, causing a progressive loss of vision and of physical and mental skills. Pla2g6 mutation is the underlying genetic defect, but rare genetic heterogeneity has been demonstrated. Infantile neuroaxonal dystrophy jama neurology jama network. Infantile neuroaxonal dystrophy inad is a rare neurodegenerative disorder. We aim to outline the natural history of inad and provide a comprehensive description of its clinical, radiological, laboratory, and. Pdf infantile neuroaxonal dystrophy inad is a rare neurodegenerative disease that often cuts short the life span. Evidence showed that a large proportion of patients with infantile neuroaxonal dystrophy have a mutation in the pla2g6 gene. Neuroaxonal dystrophy in dogs symptoms, causes, diagnosis. Infantile neuroaxonal dystrophy inad is a rare neurodegenerative disease with early onset. Infantile neuroaxonal dystrophy inad is a rare inherited disease whereby both the parents are carrier and thus the chances of one of their child having infantile neuroaxonal dystrophy is 25%.
Infantile neuroaxonal dystrophy inad mim 256600 is a neurodegenerative disease characterized by. Infantile neuroaxonal dystrophy genetic and rare diseases nih. Common clinical, radiologic, and pathologic features in infantile neuroaxonal dystrophy inad and pantothenate kinaseassociated neurodegeneration pkan have led to the hypothesis of an allelic relationship. With a typical onset at 6 months of age, inad is characterized by regression of acquired motor skills, delayed motor coordination and eventual loss of voluntary muscle control. Analysis of pla2g6 gene variant in a family affected with infantile neuroaxonal dystrophy. Biallelic mutations in the pla2g6 gene have been identified. Infantile neuroaxonal dystrophy and pla2g6associated. Juvenile neuroaxonal dystrophy article about juvenile. Clinical study and pla2g6 mutation screening analysis in. Infantile neuroaxonal dystrophy is a disorder that primarily affects the nervous system. A child who shows progressive motor and mental deterioration after the first year of life, who has pyramidal signs, marked muscle hypotonia, but no seizures, suggests to have infantile neuroaxonal dystrophy inad.
Even though both parents pass this gene on to their child, which results in the child inheriting two mutated. From ghr infantile neuroaxonal dystrophy is a disorder that primarily affects the nervous system. Pdf infantile neuroaxonal dystrophy inad is a rare neurodegenerative disease that often cuts short the life span of a child to 10 years. Infantile neuroaxonal dystrophy caused by pla2g6 gene mutation. Find out information about juvenile neuroaxonal dystrophy. Is there any treatment for infantile neuroaxonal dystrophy. Infantile neuroaxonal dystrophy inad is a rapidly progressive neurodegenerative disorder of early onset causing premature death. Infantile neuroaxonal dystrophy inad 1 is a rare inherited disorder that affects the nervous system.
It results from biallelic pathogenic variants in pla2g6, which encodes a calciumindependent phospholipase a2. Infantile neuroaxonal dystrophy inad is an autosomal recessive disorder with mutations in the pla2g6 gene, which encodes a calciumindependent phospholipase a2, on chromosome 22q. Infantile neuroaxonal dystrophy 1 baylor college of medicine. Symptoms typically begin to appear between six months and three years of age. This results in total neurological degeneration and mortality by the age of 10. Based on an individuals age of onset and symptoms, their disease may be classified as one of three types of plan. The diagnosis of inad is difficult due to the frequent occurrence of atypical cases and lack of specific early signs. Infantile neuroaxonal dystrophy medigoo health medical tests. Enable javascript to view the expandcollapse boxes. This struck me particularly hard since lewy body disease is similar in certain respects to infantile neuroaxonal dystrophy inad, the condition two of katherines doctors believe she likely suffers from. It was the second pregnancy of this healthy, noncon sanguineous couple. The neuropathological findings of a sporadic case of infantile neuroaxonal dystrophy inad are reported who died at an earlier age than any of the previously recorded ones. Six patients aged 19 months to 9 years with proved neuroaxonal dystrophy one with the infantile form, five juvenile forms underwent imaging at 1.
Infantile neuroaxonal dystrophy jama neurology jama. Inad and duchenne muscular dystrophy, two ends of the ipla2i. Infantile neuroaxonal dystrophy inad is a rare inherited disorder which affects the nerve axons in the brain and other parts of the body, causing progressive loss of. The diffusionweighted and conventional mr imaging findings are reported for six cases. Mri in infantile neuroaxonal dystrophy pediatric neurology.
Infantile neuroaxonal dystrophy is a disease entity first described by seitelberger in 1952. Nbia and inad are very similar, involving widespread neurodegeneration that begins within the first 12 years of life. Recently, it was reported that mutations in the pla2g6 gene cause inad, but neuropathological analysis of genetically confirmed individuals with neuroaxonal. Infantile neuroaxonal dystrophyatypical neuroaxonal dystrophy inadatypical nad is a type of neurodegeneration with brain iron accumulation nbia. One of the conditions which qualify for a compassionate allowance there are 88 listed conditions in all is infantile neuroaxonal dystrophy, a rare genetic neurological disorder. The payee may view, download, andor print the article for his. Biallelic mutations in the pla2g6 gene have been identified as the most frequent. Infantile neuroaxonal dystrophy inad is an autosomal recessive progressive neurodegenerative.
Infantile neuroaxonal dystrophy article about infantile. The authors excluded linkage in one consanguineous inad family by haplotype analysis. A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for infantile neuroaxonal. Neuroaxonal dystrophy in dogs is a usually caused by genetics. Diffusionweighted and conventional mr imaging findings of. Infantile neuroaxonal dystrophy inad is a rare autosomal recessive neurodegenerative disorder, characterized by an early symptomatic onset with rapid progression of psychomotor regression and hypotonia, evolving into spasticity. It affects axons, the part of a nerve cell that carries messages from the brain to other parts of the body, and causes progressive loss of vision, muscular control, and mental skills.
Infantile neuroaxonal dystrophy is a genetic condition that is inherited in an autosomal recessive pattern. Their 7 yearold daughter was affected with infantile neuroaxonal dystrophy. Infantile neuroaxonal dystrophy an overview sciencedirect topics. Infantile neuroaxonal dystrophy inad is a rare inherited disorder which affects the nerve axons in the brain and other parts of the body, causing progressive loss of vision, physical and mental skills. Feb 07, 2018 infantile neuroaxonal dystrophy is a type of lipid storage disorder that mostly affects the nervous system. Infantile neuroaxonal dystrophy genetics home reference. Infantile neuroaxonal dystrophy inad is a rare inherited neurological disorder. The condition is inherited and affects the nerve cells that carry messages from the brain to the other parts of the childs body.
Professor alexis brice 1department of child neurology, national neurological institute carlo besta, via celoria 11, 203. This in turn causes loss of mental skills, muscle control, and vision. Infantile neuroaxonal dystrophy clinical, pathologic, and histochemical findings in a family with 3 affected siblings. Individuals with infantile neuroaxonal dystrophy typically do not have any symptoms at birth, but between the ages of about 6 and 18 months they begin to experience delays in acquiring new motor and intellectual skills, such as crawling or beginning to speak. Both the sire and the dam must be carriers of the mutated gene. Successful clinical application of preimplantation genetic diagnosis for infantile neuroaxonal dystrophy. Novel pla2g6 mutations associated with an exonic deletion. Infantile neuroaxonal dystrophy inad is an autosomal recessive disorder with mutations in the pla2g6 gene, which encodes a calciumindependent. In addition to nonspecific dystrophic changes of the axons, the schwann cells contained several distinct bodies which were composed of stacks of irregularly disposed membranes. Abnormal schwann cell inclusion is reported in biopsied peripheral nerve in a cases of infantile neuroaxonal dystrophy. The characteristic histopathological features were the following. It is seen between the age of 618 months or it can also occur in late teenage. Infantile neuroaxonal dystrophy inad is a rare autosomalrecessive neurodegenerative disorder.
Infantile neuroaxonal dystrophy affects the axons, which carry messages to the body from the brain. A familial disease of the central nervous system occurring early in life and characterized by axonal swellings, arrested development, atrophy of the optic. Click on the link to view a sample search on this topic. Monozygotic twins with infantile neuroaxonal dystrophy. Monozygotic twins with infantile neuroaxonal dystrophy spandidos. Infantile neuroaxonal dystrophy, also referred to as inad, is a rare neurological disorder that is usually diagnosed within the first two years of a childs life.
The natural history of infantile neuroaxonal dystrophy. We aim to outline the natural history of inad and provide a comprehensive description of its clinical, radiological, laboratory, and molecular findings. Clinical features of infantile neuroaxonal dystrophy and. A m wang, d schindler, and r desnick division of medical and molecular genetics, mount sinai school of medicine, new york 10029.
There were no abnormalities at birth, and both children had low muscle strength and tension on admission. Infantile neuroaxonal dystrophy is a rare autosomalrecessive neurodegenerative disorder with onset in the first and second year of life. These clinical syndromes display two significantly different disease phenotypes. The findings suggested increased metal deposition in the globus pallidus. Doctors can prescribe medications for pain relief and sedation. Inheritance is believed to be autosomal recessive, which means two copies of the mutated gene must be present for the disease to be passed onto the litter. It has two forms, a classic form and an atypical form.
Recessive mutations in pla2g6 have been associated with different neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation and more recently, earlyonset dystonia parkinsonism. Infantile neuroaxonal dystrophy caused by pla2g6 gene mutation in a. In spite of extensive pathologic and clinical descriptions the exact nature of the lesions is not yet defined, and the classification of this nosologic entity is still not clear. Infantile neuroaxonal dystrophy and pantothenate kinase. Infantile neuroaxonal dystrophy information page national. The first page of the pdf of this article appears above. A 6yearold boy with the typical clinical features of infantile neuroaxonal dystrophy was examined with magnetic resonance imaging. While the basic genetic and metabolic causes are unknown, inad is the result of.
In most cases, the first symptoms appear during the first two years of a childs life and include loss of physical skills he or she had previously mastered, such as head. It is characterized by a progressive motor and mental deterioration, bilateral pyramidal tract signs, marked hypotonia. With the discovery of the gene defect in pkan, this can now be tested directly. There is no cure for infantile neuroaxonal dystrophy inad and no treatment that can stop the progress of the disease. Pubmed is a searchable database of medical literature and lists journal articles that discuss osteopetrosis and infantile neuroaxonal dystrophy. Infantile neuroaxonal dystrophy atypical neuroaxonal dystrophy inadatypical nad is a type of neurodegeneration with brain iron accumulation nbia. Infantile neuroaxonal dystrophy medigoo health medical.
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