Delayed speech and language development, and Depressivity

High match PARKINSON DISEASE 1, AUTOSOMAL DOMINANT; PARK1

Parkinson disease is the second most common neurogenic disorder after Alzheimer disease (AD ), affecting approximately 1% of the population over age 50. Clinical manifestations include resting tremor, muscular rigidity, bradykinesia, and postural instability. Additional features are characteristic postural abnormalities, dysautonomia, dystonic cramps, and dementia (Polymeropoulos et al., 1996).For a general phenotypic description and a discussion of genetic heterogeneity of Parkinson disease, see {168600}.

PARKINSON DISEASE 1, AUTOSOMAL DOMINANT; PARK1 Is also known as parkinson disease 1, autosomal dominant lewy body

• Autosomal dominant inheritance
• Pica
• Spasticity
• Delayed speech and language development
• Hyperreflexia

SOURCES: DOID UMLS OMIM MESH MONDO

High match MIGRAINE, FAMILIAL HEMIPLEGIC, 2; FHM2

MIGRAINE, FAMILIAL HEMIPLEGIC, 2; FHM2 Is also known as mhp2

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Pica

SOURCES: UMLS OMIM MONDO GARD

High match HUNTINGTON DISEASE-LIKE 1; HDL1

HUNTINGTON DISEASE-LIKE 1; HDL1 Is also known as huntington-like neurodegenerative disorder 1;hln1, huntington-like neurodegenerative disorder, autosomal dominant, prion disease, early-onset, with prominent psychiatric features;early-onset prion disease with prominent psychiatric features; hdl1

• Autosomal dominant inheritance
• Seizures
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: UMLS OMIM MONDO ORPHANET DOID MESH

High match ACERULOPLASMINEMIA

Aceruloplasminemia is an adult-onset disorder of neurodegeneration with brain iron accumulation (NBIA; see this term) characterized by anemia, retinal degeneration, diabetes and various neurological symptoms.

ACERULOPLASMINEMIA Is also known as ;hereditary ceruloplasmin deficiency

• Autosomal recessive inheritance
• Ataxia
• Anemia
• Delayed speech and language development
• Dysarthria

SOURCES: GARD SCTID UMLS OMIM MONDO DOID ORPHANET

High match HYPERPHENYLALANINEMIA, BH4-DEFICIENT, A; HPABH4A

Tetrahydrobiopterin (BH4)-deficient hyperphenylalaninemia (HPA) comprises a genetically heterogeneous group of progressive neurologic disorders caused by autosomal recessive mutations in the genes encoding enzymes involved in the synthesis or regeneration of BH4. BH4 is a cofactor for phenylalanine hydroxylase (PAH ), tyrosine hydroxylase (TH ) and tryptophan hydroxylase (TPH1 ), the latter 2 of which are involved in neurotransmitter synthesis. The BH4-deficient HPAs are characterized phenotypically by hyperphenylalaninemia, depletion of the neurotransmitters dopamine and serotonin, and progressive cognitive and motor deficits (Dudesek et al., 2001).HPABH4A, caused by mutations in the PTS gene, represents the most common cause of BH4-deficient hyperphenylalaninemia (Dudesek et al., 2001). Other forms of BH4-deficient HPA include HPABH4B (OMIM ), caused by mutation in the GCH1 gene (OMIM ), HPABH4C (OMIM ), caused by mutation in the QDPR gene (OMIM ), and HPABH4D (OMIM ), caused by mutation in the PCBD1 gene (OMIM ). Niederwieser et al. (1982) noted that about 1 to 3% of patients with hyperphenylalaninemia have one of these BH4-deficient forms. These disorders are clinically and genetically distinct from classic phenylketonuria (PKU ), caused by mutation in the PAH gene.Two additional disorders associated with BH4 deficiency and neurologic symptoms do not have overt hyperphenylalaninemia as a feature: dopa-responsive dystonia (OMIM ), caused by mutation in the SPR gene (OMIM ), and autosomal dominant dopa-responsive dystonia (DYT5 ), caused by mutation in the GCH1 gene. Patients with these disorders may develop hyperphenylalaninemia when stressed.

HYPERPHENYLALANINEMIA, BH4-DEFICIENT, A; HPABH4A Is also known as hyperphenylalaninemia, tetrahydrobiopterin-deficient, due to pts deficiency, 6-pyruvoyl-tetrahydropterin synthase deficiency, pts deficiency;hyperphenylalaninemia due to 6-pyruvoyltetrahydropterin synthase deficiency

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: NCIT OMIM ORPHANET MONDO DOID MESH GARD UMLS

High match MACROCEPHALY/MEGALENCEPHALY SYNDROME, AUTOSOMAL RECESSIVE; MGCPH

Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Cognitive impairment

SOURCES: OMIM UMLS MONDO MESH GARD

High match CHROMOSOME 15q11-q13 DUPLICATION SYNDROME

The features of the chromosome 15q11-q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delays, and behavioral problems (Bundey et al., 1994; Burnside et al., 2011).See also chromosome 15q13.3 deletion syndrome (OMIM ) and chromosome 15q11.2 deletion syndrome (OMIM ).For a discussion of genetic heterogeneity of autism, see {209850}.

CHROMOSOME 15q11-q13 DUPLICATION SYNDROME Is also known as duplication 15q11-q13 syndrome;15q11-q13 duplication syndrome; 15q11-q13 microduplication syndrome; 15q11q13 duplication syndrome; dup(15)(q11q13); trisomy 15q11-q13; trisomy 15q11q13

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: NCIT SCTID MONDO OMIM ORPHANET UMLS

High match NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4; NBIA4

Neurodegeneration with brain iron accumulation-4 (NBIA4) is an autosomal recessive neurodegenerative disorder characterized by progressive spastic paraplegia, parkinsonism unresponsive to L-DOPA treatment, and psychiatric or behavioral symptoms. Other neurologic features, including optic atrophy, eye movement abnormalities, dystonia, dysphagia, dysarthria, and motor axonal neuropathy, may occur. Brain MRI shows T2-weighted hypointensities in the globus pallidus and substantia nigra. Onset is usually in the first 2 decades, but later onset has been reported (summary by Dogu et al., 2013). There is phenotypic variation: some patients may not have extrapyramidal signs and may have muscle weakness and atrophy as well as cognitive impairment or developmental delay (Deschauer et al., 2012)For a general phenotypic description and a discussion of genetic heterogeneity of NBIA, see NBIA1 (OMIM ).

NEURODEGENERATION WITH BRAIN IRON ACCUMULATION 4; NBIA4 Is also known as mitochondrial protein-associated neurodegeneration;mpan;mpan; nbia due to c19orf12 mutation; nbia4; neurodegeneration with brain iron accumulation due to c19orf12 mutation; neurodegeneration with brain iron accumulation type 4

• Autosomal recessive inheritance
• Seizures
• Global developmental delay
• Pica
• Ataxia

SOURCES: OMIM DOID SCTID GARD UMLS ORPHANET MONDO

High match HUNTINGTON DISEASE; HD

Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dystonia, incoordination, cognitive decline, and behavioral difficulties. There is progressive, selective neural cell loss and atrophy in the caudate and putamen. Walker (2007) provided a detailed review of Huntington disease, including clinical features, population genetics, molecular biology, and animal models.

HUNTINGTON DISEASE; HD Is also known as huntington chorea;huntington chorea

• Autosomal dominant inheritance
• Seizures
• Pica
• Ataxia
• Cognitive impairment

SOURCES: ORPHANET OMIM UMLS ICD10 SCTID

Medium match MACHADO-JOSEPH DISEASE; MJD

Machado-Joseph disease, named for affected families of Azorean extraction, is an autosomal dominant progressive neurologic disorder characterized principally by ataxia, spasticity, and ocular movement abnormalities. Although independently described as a seemingly separate disorder, spinocerebellar ataxia-3 is now known to be the same as Machado-Joseph disease.Three classic clinical subtypes of MJD are recognized: type 1 with early onset and marked pyramidal and dystonic signs; type 2, or pure, with predominant cerebellar ataxia; and type 3 with later-onset and peripheral neuropathy (Franca et al., 2008).

MACHADO-JOSEPH DISEASE; MJD Is also known as spinocerebellar ataxia 3;sca3, spinocerebellar atrophy iii, azorean neurologic disease, spinopontine atrophy, nigrospinodentatal degeneration

• Autosomal dominant inheritance
• Pica
• Ataxia
• Nystagmus
• Ptosis

SOURCES: UMLS OMIM ORPHANET SCTID