May 03, 2022; 98 (18 Supplement) Sunday, April 3 First published May 3, 2022, Abstract Objective: To present a rare mitochondrial cytopathy in 3 siblings with variable age and clinical features at presentation. [n.neurology.org]

Case Presentation: Herein, we present the first case of HAYOS in Saudi Arabia. A 3-month-old girl presented with global developmental delay, hypotonia, bilateral severe sensorineural hearing loss, and vision impairment. [bibliomed.org]

Introduction High resolution ultrasonography (US) has been used for diagnosis and evaluation of entrapment peripheral neuropathy… Reticular pseudodrusen (RPD) could be present not only in the posterior pole but extramacular area also as a confluent… Ayoung [semanticscholar.org]

496790 Classification level: Disorder Synonym(s): Harel-Yoon syndrome Prevalence: <1 / 1 000 000 Inheritance: - Age of onset: Neonatal, Infancy ICD-10: E88.8 OMIM: 617183 UMLS: - MeSH: - GARD: - MedDRA: - The documents contained in this web site are presented [orpha.net]

Pure HSP presents with spasticity in the lower limbs, associated with neurogenic bladder disturbance as well as lack of vibration sensitivity (pallhypesthesia). [en.wikipedia.org]

• Developmental Delay

  Genes related to Optic Atrophy-peripheral Neuropathy-developmental Delay Syndrome ATAD3A View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Optic Atrophy-peripheral Neuropathy-developmental Delay Syndrome [mendelian.co]

  A 3-month-old girl presented with global developmental delay, hypotonia, bilateral severe sensorineural hearing loss, and vision impairment. Brain magnetic resonance imaging showed mild brain atrophy and delayed myelination. [bibliomed.org]

  Patients have extra-cardiac manifestations, including severe developmental delay, ectodermal ... [kegg.jp]

  delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy ATAD3A in Intellectual disability Level 3: [panelapp.genomicsengland.co.uk]

  Description Harel-Yoon syndrome (HAYOS) is a neurological syndrome characterized by global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. [genome.jp]

• Disability

  All had severely delayed psychomotor development with intellectual disability and poor or absent speech. [findzebra.com]

  Harel-Yoon syndrome is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy. [ncbi.nlm.nih.gov]

  Mendelian Rare Diseases HAREL-YOON SYNDROME; HAYOS Optic Atrophy-peripheral Neuropathy-developmental Delay Syndrome Description Harel-Yoon syndrome is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability [mendelian.co]

  Patients are with overgrowth, facial dysmorphism and intellectual disability. EED is a member of the polycomb repressive ... [kegg.jp]

• Weakness

  The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. [ncbi.nlm.nih.gov]

  A form of mitochondrial disease, Harel-Yoon Syndrome (HYS) is a neurodevelopmental disorder characterized by developmental delay, hypotonia (weak muscle tone), spasticity (rigid/stiff muscles), hypertrophic cardiomyopathy (thick heart) optic nerve atrophy [charlieourangel.wordpress.com]

  This also results in brisk reflexes, extensor plantar reflexes, muscle weakness, and variable bladder disturbances. [en.wikipedia.org]

  […] recessive 18 615356 TRAPPC2 chrX Xp22.2-p22.1 Spondyloepiphyseal dysplasia tarda 313400 TRAPPC9 chr8 8q24.3 Mental retardation autosomal recessive 13 613192 TRDN chr6 6q22-q23 Ventricular tachycardia catecholaminergic polymorphic 5 with or without muscle weakness [institutobernabeu.com]

• Falling

  Thirty year old second sibling with normal and initial development, had sudden onset recurrent falls and ataxia at the age of 3 years followed by rapid worsening which led to bed ridden status. Within few years with severe truncal hypotonia. [n.neurology.org]

  So last Friday when Charlie’s geneticist said HYS falls under the mitochondrial disease umbrella I was confused. While I don’t fully understand it.. [charlieourangel.wordpress.com]

  […] anemia nonspherocytic due to glucose phosphate isomerase deficiency 613470 GPIHBP1 chr8 8q24.3 Hyperlipoproteinemia type 1D 615947 GPNMB chr7 7p15.3 Amyloidosis primary localized cutaneous 3 617920 GPR143 chrX Xp22.3 Ocular albinism type I Nettleship-Falls [institutobernabeu.com]

• Epilepsy

  […] others 300419 ARX chrX Xp22.13 Partington syndrome 309510 ARX chrX Xp22.13 Hydranencephaly with abnormal genitalia 300215 ASAH1 chr8 8p22-p21.3 Farber lipogranulomatosis 228000 ASAH1 chr8 8p22-p21.3 Spinal muscular atrophy with progressive myoclonic epilepsy [institutobernabeu.com]

  30471716 Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation, 618325 Added comment: Added MACF1 to 'Cerebellar hypoplasia' panel on advice from Helen Brittain after MACF1 was reviewed by Sarah Leigh on the 'Genetic Epilepsy [panelapp.genomicsengland.co.uk]

  These include: peripheral neuropathy, amyotrophy, ataxia, intellectual disability, ichthyosis, epilepsy, optic neuropathy, dementia, deafness, or problems with speech, swallowing or breathing.[14] Anita Harding[7] classified the HSP in a pure and complicated [en.wikipedia.org]

• Fecal Incontinence

  Thirty four year old first sibling with normal birth and delayed development in all domains suddenly worsened since last 2 years developed gait ataxia with psychiatric manifestations, urinary and fecal incontinence. [n.neurology.org]

• Suggestibility

  MRI Brain suggestive symmetrical basal ganglionic T2 hyper-intensities. Family history suggestive of almost similar complaints in both the elder sisters at an early age. [n.neurology.org]

  These findings suggested that the mutation acts as a toxic gain-of-function allele and results in decreased mitochondria in neurons and muscle. [findzebra.com]

  The current information in the literature does not support a Green rating as suggested by external reviewer, there are not sufficient cases, only an animal model (PMID:31136762) 20 Sep 2019 Cerebellar hypoplasia v1.37 NMNAT2 Louise Daugherty Gene: nmnat2 [panelapp.genomicsengland.co.uk]

• Psychiatric Manifestation

  Followed by patient developed psychiatric manifestations including suicidal tendencies. MRI Brain suggestive symmetrical basal ganglionic T2 hyper-intensities. [n.neurology.org]

• Incontinence

  Thirty four year old first sibling with normal birth and delayed development in all domains suddenly worsened since last 2 years developed gait ataxia with psychiatric manifestations, urinary and fecal incontinence. [n.neurology.org]

• Seizure

  Generalized non-motor (absence) seizure MedGen UID: 1385688 •Concept ID: C4316903 • Disease or Syndrome A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. [ncbi.nlm.nih.gov]

  Both patients developed absence seizures around 6 to 7 years of age. Other features included mildly delayed puberty and delayed bone age. Brain imaging showed progressive cerebellar atrophy and hypoplastic optic nerves. [findzebra.com]

  Other variable features are spasticity, seizures, ataxia, congenital cataract, and dysmorphic facial features. Age of onset is in the neonatal period or infancy. [orpha.net]

  Atrophy-peripheral Neuropathy-developmental Delay Syndrome ATAD3A View recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Optic Atrophy-peripheral Neuropathy-developmental Delay Syndrome Intellectual disability Seizures [mendelian.co]

• Global Developmental Delay

  Description Harel-Yoon syndrome (HAYOS) is a neurological syndrome characterized by global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy. [genome.jp]

  A 3-month-old girl presented with global developmental delay, hypotonia, bilateral severe sensorineural hearing loss, and vision impairment. Brain magnetic resonance imaging showed mild brain atrophy and delayed myelination. [bibliomed.org]

  […] system Cerebellar ataxia Cerebellar atrophy Delayed speech and language development Dystonic disorder Generalized non-motor (absence) seizure Global developmental delay Inability to walk Intellectual disability Peripheral axonal neuropathy Reduced brain [ncbi.nlm.nih.gov]

  developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy ATAD3A disorder - global developmental delay, hypotonia, optic atrophy, axonal neuropathy, and hypertrophic cardiomyopathy ATAD3A in Intellectual disability [panelapp.genomicsengland.co.uk]

  Homepage Rare diseases Search Search for a rare disease Disease definition A rare mitochondrial disease characterized by signs and symptoms within a phenotypic and metabolic spectrum that includes global developmental delay, hypotonia, intellectual disability [orpha.net]

• Ataxia

  On examination cerebellar ataxia and absent DTR were present. MRI Brain suggestive of diffuse symmetrical cerebellar atrophy with T2 hyperintensities in bilateral cerebral peduncles. [n.neurology.org]

  […] recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Optic Atrophy-peripheral Neuropathy-developmental Delay Syndrome Intellectual disability Seizures Global developmental delay Generalized hypotonia Scoliosis Ataxia [mendelian.co]

  Cerebellar ataxia MedGen UID: 849 •Concept ID: C0007758 • Disease or Syndrome Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. [ncbi.nlm.nih.gov]

  autosomal recessive 16 615768 to Autosomal recessive spinocerebellar ataxia type 16, OMIM:615768; autosomal recessive spinocerebellar ataxia 16, MONDO:0014339; Spinocerebellar ataxia 48, OMIM:618093; spinocerebellar ataxia 48, MONDO:0032526 13 Sep 2022 [panelapp.genomicsengland.co.uk]

• Peripheral Neuropathy

  […] disability, truncal hypotonia, spasticity, and peripheral neuropathy. [mendelian.co]

  Introduction High resolution ultrasonography (US) has been used for diagnosis and evaluation of entrapment peripheral neuropathy… Reticular pseudodrusen (RPD) could be present not only in the posterior pole but extramacular area also as a confluent… Ayoung [semanticscholar.org]

  Harel-Yoon syndrome is a syndromic neurodevelopmental disorder characterized by delayed psychomotor development, intellectual disability, truncal hypotonia, spasticity, and peripheral neuropathy. [ncbi.nlm.nih.gov]

  Communities, advocacy groups, and support organizations for Optic atrophy-peripheral neuropathy-developmental delay syndrome. [rarediseases.oscar.ncsu.edu]

  It can be characterised by delayed psychomotor development, intellectual disability, truncal hypotonia (reduced muscle strength), spasticity (contracted and stiff muscles), and peripheral neuropathy (nerve damage). [gulfnews.com]

• Nystagmus

  […] homeostasis Increased serum lactate Abnormality of the cardiovascular system Hypertrophic cardiomyopathy Abnormality of the digestive system Feeding difficulties Abnormality of the eye Corneal opacity Deeply set eye Developmental cataract Esotropia Myopia Nystagmus [ncbi.nlm.nih.gov]

  […] recommended genes panels Clinical Features Top most frequent phenotypes and symptoms related to Optic Atrophy-peripheral Neuropathy-developmental Delay Syndrome Intellectual disability Seizures Global developmental delay Generalized hypotonia Scoliosis Ataxia Nystagmus [mendelian.co]

  Additional variable features included poor feeding, sleep difficulties, myopia, nystagmus, and esotropia. Some patients had skeletal anomalies, such as pectus carinatum, scoliosis, hip dysplasia, or foot deformities. [findzebra.com]

  CRSD is characterized by congenital nystagmus, stable low vision, photophobia, and a normal fundus appearance ... [kegg.jp]

They offer help in all different aspects of how a rare disease can affect the daily routine of the family, from where to get special supplies to what the latest treatment is for a given condition. [rarediseases.oscar.ncsu.edu]

The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment. [orpha.net]

[citation needed] 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 other reason I wanted a diagnosis so badly is because if someone took the time to discover this syndrome then that means someone is researching possible treatments. Dr. [charlieourangel.wordpress.com]

[citation needed] 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]

The majority of individuals with HSP have a normal life expectancy.[14] Epidemiology[edit] Worldwide, the prevalence of all hereditary spastic paraplegias combined is estimated to be 2 to 6 in 100,000 people.[32] A Norwegian study of more than 2.5 million [en.wikipedia.org]

POLR3A 10q22.3 Autosomal recessive Pathophysiology[edit] The major feature of HSP is a length-dependent axonal degeneration.[19] These include the crossed and uncrossed corticospinal tracts to the legs and fasciculus gracilis. [en.wikipedia.org]

HYS doesn’t fall under one of the 5 mitochondrial disease complexes, but it is a mitochondrial disease in that Charlie’s mutation on the ATAD3A gene prevents energy from transporting into Charlie’s cells and organs necessary to thrive. [charlieourangel.wordpress.com]

[citation needed] 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]