Delayed speech and language development, and Optic atrophy

Medium match VITAMIN B12-UNRESPONSIVE METHYLMALONIC ACIDEMIA TYPE MUT0

Vitamin B12-unresponsive methylmalonic acidemia type mut0 is an inborn error of metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which does not respond to administration of vitamin B12.

VITAMIN B12-UNRESPONSIVE METHYLMALONIC ACIDEMIA TYPE MUT0 Is also known as complete deficiency of methylmalonyl-coa mutase; vitamin b12-unresponsive methylmalonic aciduria type mut0

• Intellectual disability
• Global developmental delay
• Growth delay
• Muscular hypotonia
• Anemia

SOURCES: UMLS ORPHANET

Medium match MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 4; MMDS4

MULTIPLE MITOCHONDRIAL DYSFUNCTIONS SYNDROME 4; MMDS4 Is also known as ;

• Autosomal recessive inheritance
• Spasticity
• Optic atrophy
• Absent speech
• Leukodystrophy

SOURCES: OMIM MONDO ORPHANET UMLS DOID

Medium match AUDITORY NEUROPATHY AND OPTIC ATROPHY; ANOA

ANOA is an autosomal recessive neurologic disorder characterized by onset of visual and hearing impairment in the first or second decades (summary by Paul et al., 2017).

• Hearing impairment
• Nystagmus
• Visual impairment
• Peripheral neuropathy
• Delayed speech and language development

SOURCES: OMIM

Medium match SPASTIC ATAXIA 4, AUTOSOMAL RECESSIVE; SPAX4

SPASTIC ATAXIA 4, AUTOSOMAL RECESSIVE; SPAX4 Is also known as ;autosomal recessive spastic ataxia type 4; spax4

• Autosomal recessive inheritance
• Ataxia
• Nystagmus
• Motor delay
• Delayed speech and language development

SOURCES: ORPHANET UMLS DOID GARD OMIM MONDO

Medium match SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 12; SCAR12

Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency is a rare autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome characterized by early-childhood onset of cerebellar ataxia associated with generalized tonic-clonic epilepsy and psychomotor development delay, dysarthria, gaze-evoked nystagmus and learning disability. Other features in some patients include upper motor neuron signs with leg spasticity and extensor plantar responses, and mild cerebellar atrophy on brain MRI.

SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 12; SCAR12 Is also known as spinocerebellar ataxia with mental retardation and epilepsy;autosomal recessive spinocerebellar ataxia type 12; scar12

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Microcephaly

SOURCES: MONDO ORPHANET UMLS OMIM DOID

Medium match CEROID LIPOFUSCINOSIS, NEURONAL, 2; CLN2

The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure. The lipopigment pattern seen most often in CLN2 consists of 'curvilinear' profiles (Mole et al., 2005).For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (OMIM ).

CEROID LIPOFUSCINOSIS, NEURONAL, 2; CLN2 Is also known as ceroid lipofuscinosis, neuronal, 2, variable age at onset, jansky-bielschowsky disease

• Autosomal recessive inheritance
• Seizures
• Pica
• Ataxia
• Visual impairment

SOURCES: OMIM

Medium match NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 5; NBIA5

NBIA5, sometimes referred to as 'static encephalopathy of childhood with neurodegeneration in adulthood (SENDA),' is an X-linked neurodegenerative disorder characterized by global developmental delay in early childhood that is essentially static, with slow motor and cognitive gains until adolescence or early adulthood. In young adulthood, affected individuals develop progressive dystonia, parkinsonism, extrapyramidal signs, and dementia resulting in severe disability. Brain MRI shows iron accumulation in the globus pallidus and substantia nigra. A characteristic finding is T1-weighted hyperintensity surrounding a central band of hypointensity in the substantia nigra. Cerebral and cerebellar atrophy are also observed (summary by Haack et al., 2012 and Saitsu et al., 2013).For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (OMIM ).

NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 5; NBIA5 Is also known as beta-propeller protein-associated neurodegeneration;bpan, static encephalopathy of childhood with neurodegeneration in adulthood;senda;bpan; nbia5; neurodegeneration with brain iron accumulation type 5; senda; static encephalopathy of childhood with neurdegeneration in adulthood

• Intellectual disability
• Seizures
• Global developmental delay
• Motor delay
• Spasticity

SOURCES: SCTID DOID ORPHANET GARD OMIM MONDO UMLS

Medium match STRIATONIGRAL DEGENERATION, INFANTILE; SNDI

Bilateral striatal necrosis (BSN) encompasses a heterogeneous group of neurologic disorders with different causation. Familial infantile striatal degeneration is rare and can be inherited as an autosomal recessive or mitochondrial (see {500003}) disorder. The familial form has an insidious onset and a slowly progressive course; the sporadic form is associated with acute systemic illness. Many features of BSN overlap with Leigh syndrome (OMIM ) and certain metabolic disorders, including glutaric acidemia I (OMIM ) and methylmalonic aciduria (OMIM ). See also Aicardi-Goutieres syndrome (OMIM ) (Mito et al., 1986; De Meirleir et al., 1995). Genetic Heterogeneity of Stiatonigral DegenerationChildhood-onset striatonigral degeneration (OMIM ) is caused by mutation in the VAC14 gene (OMIM ) on chromosome 16q22.See also adult-onset autosomal dominant striatal degeneration (ADSD ), caused by mutation in the PDE8B gene (OMIM ) on chromosome 5q13.

STRIATONIGRAL DEGENERATION, INFANTILE; SNDI Is also known as infantile bilateral striatal necrosis;ibsn, bilateral striatal necrosis, infantile, striatal degeneration, familial

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Ataxia
• Nystagmus

SOURCES: OMIM ORPHANET

Medium match EPILEPSY, PROGRESSIVE MYOCLONIC, 3, WITH OR WITHOUT INTRACELLULAR INCLUSIONS; EPM3

Mutations in the KCTD7 gene cause a severe neurodegenerative phenotype characterized by onset of intractable myoclonic seizures before age 2 years and accompanied by developmental regression. The initial description was consistent with a form of progressive myoclonic epilepsy (designated here as EPM3), whereas a later report identified intracellular accumulation of autofluorescent lipopigment storage material, consistent with neuronal ceroid lipofuscinosis (designated CLN14). Ultrastructural findings on skin biopsies thus appear to be variable. However, clinical features are generally consistent between reports (summary by Staropoli et al., 2012).For a general phenotypic description and a discussion of genetic heterogeneity of progressive myoclonic epilepsy, see EPM1A (254800).For a general phenotypic description and a discussion of genetic heterogeneity of neuronal ceroid lipofuscinosis, see CLN1 (OMIM ).

EPILEPSY, PROGRESSIVE MYOCLONIC, 3, WITH OR WITHOUT INTRACELLULAR INCLUSIONS; EPM3 Is also known as ceroid lipofuscinosis, neuronal, 14;cln14;epm3; pme type 3; progressive myoclonic epilepsy due to kctd7 deficiency; progressive myoclonus epilepsy type 3

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Microcephaly
• Scoliosis

SOURCES: MESH OMIM ORPHANET GARD MONDO UMLS

Medium match 3-METHYLGLUTACONIC ACIDURIA, TYPE IX; MGCA9

MGCA9 is an autosomal recessive disorder characterized by early-onset seizures, severely delayed psychomotor development and intellectual disability. Patients have hypotonia or spasticity, and laboratory investigations show increased serum lactate and 3-methylglutaconic aciduria, suggestive of a mitochondrial defect (summary by Shahrour et al., 2017).For a phenotypic description and a discussion of genetic heterogeneity of 3-methylglutaconic aciduria, see MGCA type I (OMIM ).

3-METHYLGLUTACONIC ACIDURIA, TYPE IX; MGCA9 Is also known as ;3-methylglutaconic aciduria-epilepsy-spasticity-severe intellectual disability syndrome; mga9

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Failure to thrive

SOURCES: MONDO ORPHANET UMLS OMIM