Ataxia, and Joint stiffness

Low match PAROXYSMAL NON-KINESIGENIC DYSKINESIA

Paroxysmal non-kinesigenic dyskinesia (PNKD) is a form of paroxysmal dyskinesia (see this term), characterized by attacks of dystonic or choreathetotic movements precipitated by stress, fatigue, coffee or alcohol intake or menstruation.

PAROXYSMAL NON-KINESIGENIC DYSKINESIA Is also known as paroxysmal dystonic choreoathetosis|choreoathetosis, nonkinesigenic|pdc|dystonia 8|paroxystic non-kinesigenic choreoathetosis|dyt8|choreoathetosis, familial paroxysmal|mount-reback syndrome|fpd1

• Seizures
• Ataxia
• Spasticity
• Dysarthria
• Fatigue

SOURCES: OMIM ORPHANET MENDELIAN

Low match HEREDITARY HYPEREKPLEXIA

Hereditary hyperekplexia is a hereditary neurological disorder characterized by excessive startle responses.

HEREDITARY HYPEREKPLEXIA Is also known as hereditary hyperexplexia|familial startle disease|kok disease|startle disease, familial|stiff baby syndrome|exaggerated startle reaction|sthe|congenital stiff man syndrome|stiff-baby syndrome|stiff-person syndrome, congenital|startle reaction, exaggerated

• Intellectual disability
• Seizures
• Ataxia
• Spasticity
• Hyperreflexia

SOURCES: OMIM ORPHANET MENDELIAN

Low match ARNOLD-CHIARI MALFORMATION TYPE I

Arnold-Chiari malformation type I is a central nervous system malformation characterized by caudal displacement of the cerebellar tonsils exceeding 5mm below the foramen magnum with or without syringomyelia. Symptoms vary in onset and severity and include suboccipital headache, neck pain, vertigo, tinnitus, ocular symptoms (diplopia, blurred vision, photofobia, nystagmus), lower cranial nerve signs, cerebellar ataxia, and spasticity. Some affected individuals can be asymptomatic.

ARNOLD-CHIARI MALFORMATION TYPE I Is also known as cm1|arnold-chiari malformation type 1|chiari malformation type 1|chiari malformation type i

• Hearing impairment
• Scoliosis
• Ataxia
• Nystagmus
• Muscle weakness

SOURCES: OMIM ORPHANET MENDELIAN

Low match JABERI-ELAHI SYNDROME; JABELS

JABELS is an autosomal recessive neurodevelopmental disorder characterized by developmental delay and intellectual disability with additional variable features. Patients have onset of symptoms in infancy, but the severity is highly variable. Some patients have social interaction and learn to walk but have an ataxic gait and abnormal movements, such as tremor or dystonia, whereas others do not achieve any motor control and are unable to speak. Additional features may include retinal anomalies, visual impairment, microcephaly, abnormal foot or hand posturing, and kyphoscoliosis; some patients have dysmorphic facial features or seizures. Brain imaging typically shows cerebellar atrophy and hypoplasia of the corpus callosum (summary by Jaberi et al., 2016 and Bertoli-Avella et al., 2018).

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM MENDELIAN

Low match RETT SYNDROME

Rett syndrome (RTT) is a severe neurodevelopmental disorder affecting the central nervous system.

• Seizures
• Short stature
• Microcephaly
• Scoliosis
• Ataxia

SOURCES: ORPHANET MENDELIAN

Low match MUCOPOLYSACCHARIDOSIS, TYPE IIIA; MPS3A

The Sanfilippo syndrome, or mucopolysaccharidosis III, is an autosomal recessive lysosomal storage disease due to impaired degradation of heparan sulfate (Esposito et al., 2000). The disorder is characterized by severe central nervous system degeneration, but only mild somatic disease. Onset of clinical features usually occurs between 2 and 6 years; severe neurologic degeneration occurs in most patients between 6 and 10 years of age, and death occurs typically during the second or third decade of life. Type A has been reported (van de Kamp et al., 1981) to be the most severe, with earlier onset and rapid progression of symptoms and shorter survival. Genetic Heterogeneity of Mucopolysaccharidosis Type IIIMPS III includes 4 types, each due to the deficiency of a different enzyme: heparan N-sulfatase (type A); alpha-N-acetylglucosaminidase (type B; {252920}); acetyl CoA:alpha-glucosaminide acetyltransferase (type C; {252930}); and N-acetylglucosamine 6-sulfatase (type D; {252940}).

MUCOPOLYSACCHARIDOSIS, TYPE IIIA; MPS3A Is also known as mps iiia|sulfamidase deficiency|sanfilippo syndrome a|heparan sulfate sulfatase deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment
• Ataxia

SOURCES: OMIM MENDELIAN

Low match WOLFRAM SYNDROME

Wolfram syndrome (WS) also known as DIDMOAD, is a neurodegenerative disorder characterized by type I diabetes mellitus (DM), diabetes insipidus (DI), sensorineural deafness (D), bilateral optical atrophy (OA) and neurological signs. Other related problems are urinary tract atony, ataxia, peripheral neuropathy, psychiatric disorders and/or seizures. 2 types of WS may be distinguished: type 1 and type 2 (WS1 and WS2).

WOLFRAM SYNDROME Is also known as didmoad syndrome|diabetes insipidus-diabetes mellitus-optic atrophy-deafness syndrome

• Intellectual disability
• Seizures
• Ataxia
• Nystagmus
• Sensorineural hearing impairment

SOURCES: ORPHANET OMIM MENDELIAN

Low match MUCOPOLYSACCHARIDOSIS, TYPE IIIB; MPS3B

Sanfilippo syndrome B is an autosomal recessive lysosomal storage disorder characterized by the accumulation of heparan sulfate. Clinically, patients have progressive neurodegeneration, behavioral problems, mild skeletal changes, and shortened life span. The clinical severity ranges from mild to severe (Chinen et al., 2005).For a phenotypic description and a discussion of genetic heterogeneity of Sanfilippo syndrome, or mucopolysaccharidosis III, see MPS IIIA (OMIM ).

MUCOPOLYSACCHARIDOSIS, TYPE IIIB; MPS3B Is also known as sanfilippo syndrome b|mps iiib|n-acetyl-alpha-d-glucosaminidase deficiency|naglu deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Hearing impairment
• Ataxia

SOURCES: OMIM MENDELIAN

Low match PELIZAEUS-MERZBACHER DISEASE; PMD

Pelizaeus-Merzbacher disease is an X-linked recessive hypomyelinative leukodystrophy (HLD1) in which myelin is not formed properly in the central nervous system. PMD is characterized clinically by nystagmus, spastic quadriplegia, ataxia, and developmental delay (Inoue, 2005). Genetic Heterogeneity of Hypomyelinating LeukodystrophyOther forms of hypomyelinating leukodystrophy include HLD2 (OMIM ), caused by mutation in the GJC2/GJA12 gene (OMIM ) on chromosome 1q41; HLD3 (OMIM ), caused by mutation in the AIMP1 gene (OMIM ) on chromosome 4q24; HLD4 (OMIM ), caused by mutation in the HSPD1 gene (OMIM ) on chromosome 2q33.1; and HLD5 (OMIM ), caused by mutation in the FAM126A gene (OMIM ) on chromosome 7p15; HLD6 (OMIM ), caused by mutation in the TUBB4A gene (OMIM ) on chromosome 19p13; HLD7 (OMIM ), caused by mutation in the POLR3A gene (OMIM ) on chromosome 10q22; HLD8 (OMIM ), caused by mutation in the POLR3B gene (OMIM ) on chromosome 12q23; HLD9 (OMIM ), caused by mutation in the RARS gene (OMIM ) on chromosome 5; HLD10 (OMIM ), caused by mutation in the PYCR2 gene (OMIM ) on chromosome 1q42; HLD11 (OMIM ), caused by mutation in the POLR1C gene (OMIM ) on chromosome 6p21; HLD12 (OMIM ), caused by mutation in the VPS11 gene (OMIM ) on chromosome 11q23; HLD13 (OMIM ) caused by mutation in the HIKESHI gene (OMIM ) on chromosome 11q14; HLD14 (OMIM ), caused by mutation in the UFM1 gene (OMIM ) on chromosome 13q13; HLD15 (OMIM ), caused by mutation in the EPRS gene (OMIM ) on chromosome 1q41; HLD16 (OMIM ), caused by mutation in the TMEM106B gene (OMIM ) on chromosome 7p21; and HLD17 (OMIM ), caused by mutation in the AIMP2 gene (OMIM ) on chromosome 7p22.

PELIZAEUS-MERZBACHER DISEASE; PMD Is also known as leukodystrophy, hypomyelinating, 1|hld1

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia

SOURCES: ORPHANET OMIM MENDELIAN

Low match ALLAN-HERNDON-DUDLEY SYNDROME

Allan-Herndon-Dudley syndrome (AHDS) is an X-linked intellectual disability syndrome with neuromuscular involvement characterized by infantile hypotonia, muscular hypoplasia, spastic paraparesis with dystonic/athetoic movements, and severe cognitive deficiency.

ALLAN-HERNDON-DUDLEY SYNDROME Is also known as x-linked intellectual disability-hypotonia syndrome|t3 resistance|allan-herndon syndrome|triiodothyronine resistance|monocarboxylate transporter 8 deficiency|mct8 deficiency|mental retardation and muscular atrophy|mental retardation, x-linked, with hypoto

• Intellectual disability
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Scoliosis

SOURCES: MESH ORPHANET OMIM MENDELIAN