Visual impairment, and Brain atrophy

Low match PONTOCEREBELLAR HYPOPLASIA, TYPE 2F; PCH2F

Pontocerebellar hypoplasia type 2F is an autosomal recessive neurodevelopmental disorder characterized by progressive microcephaly and variable neurologic signs and symptoms, including cognitive and motor delay, poor or absent speech, seizures, and spasticity (summary by Breuss et al., 2016).For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (OMIM ).

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

SOURCES: OMIM MENDELIAN

Low match EPILEPTIC ENCEPHALOPATHY, INFANTILE OR EARLY CHILDHOOD, 1; IECEE1

IECEE1 is a neurodevelopmental disorder characterized by delayed psychomotor development apparent in infancy and resulting in severe to profound intellectual disability with poor or absent speech. Most patients never achieve independent walking. Patients typically have onset of refractory multifocal seizures between the first weeks and years of life, and some may show developmental regression. Additional features, such as hypotonia and cortical visual impairment, are more variable (summary by Myers et al., 2017). Genetic Heterogeneity of Infantile or Early Childhood Epileptic EncephalopathySee also IECEE2 (OMIM ), caused by mutation in the GABRB2 gene (OMIM ) on chromosome 5q34, and IECEE3 (OMIM ), caused by mutation in the ATP6V1A gene (OMIM ) on chromosome 3q13.

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

SOURCES: OMIM MENDELIAN

Low match PROGRESSIVE EPILEPSY-INTELLECTUAL DISABILITY SYNDROME, FINNISH TYPE

Progressive epilepsy-intellectual deficit, Finnish type (also known as Northern epilepsy) is a subtype of neuronal ceroid lipofuscinosis (NCL; see this term) characterized by seizures, progressive decline of intellectual capacities and variable loss of vision.

PROGRESSIVE EPILEPSY-INTELLECTUAL DISABILITY SYNDROME, FINNISH TYPE Is also known as epmr|ncl, northern epilepsy variant|epilepsy, progressive, with mental retardation|neuronal ceroid lipofuscinosis, northern epilepsy variant|cln8 disease, northern epilepsy variant|northern epilepsy

• Intellectual disability
• Seizures
• Cerebellar atrophy
• Behavioral abnormality
• Cerebral atrophy

SOURCES: OMIM ORPHANET MENDELIAN

Low match PONTOCEREBELLAR HYPOPLASIA, TYPE 2B; PCH2B

Pontocerebellar hypoplasia (PCH) represents a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. PCH type 2 is characterized by progressive microcephaly from birth combined with extrapyramidal dyskinesia and chorea, epilepsy, and normal spinal cord findings (Barth, 1993).For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (OMIM ).

• Seizures
• Generalized hypotonia
• Microcephaly
• Spasticity
• Feeding difficulties

SOURCES: OMIM MENDELIAN

Low match HYPOPREBETALIPOPROTEINEMIA, ACANTHOCYTOSIS, RETINITIS PIGMENTOSA, AND PALLIDAL DEGENERATION

HYPOPREBETALIPOPROTEINEMIA, ACANTHOCYTOSIS, RETINITIS PIGMENTOSA, AND PALLIDAL DEGENERATION Is also known as harp syndrome

• Spasticity
• Dysarthria
• Dysphagia
• Blindness
• Dystonia

SOURCES: ORPHANET OMIM MESH MENDELIAN

Low match SCHIZENCEPHALY

Brunelli et al. (1996) described schizencephaly as an extremely rare congenital disorder characterized by a full-thickness cleft within the cerebral hemispheres. The clefts are lined with gray matter and most commonly involve the parasylvian regions (Wolpert and Barnes, 1992). Large portions of the cerebral hemispheres may be absent and replaced by cerebrospinal fluid. Two types of schizencephaly have been described, depending on the size of the area involved and the separation of the cleft lips (Wolpert and Barnes, 1992). Type I schizencephaly consists of a fused cleft. This fused pial-ependymal seam forms a furrow in the developing brain, and is lined by polymicrogyric gray matter. In type II schizencephaly, there is a large defect, a holohemispheric cleft in the cerebral cortex filled with fluid and lined by polymicrogyric gray matter. The clinical manifestations depend on the severity of the lesion. Patients with type I are often almost normal; they may have seizures and spasticity. In type II abnormalities, there is usually mental retardation, seizures, hypotonia, spasticity, inability to walk or speak, and blindness.Schizencephaly may be part of the larger phenotypic spectrum of holoprosencephaly (HPE; see {236100}).

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

SOURCES: ORPHANET OMIM MENDELIAN

Low match CONGENITAL DISORDER OF GLYCOSYLATION, TYPE IAA; CDG1AA

• Seizures
• Global developmental delay
• Generalized hypotonia
• Hearing impairment
• Microcephaly

SOURCES: OMIM MENDELIAN

Low match CEROID LIPOFUSCINOSIS, NEURONAL, 4A, AUTOSOMAL RECESSIVE; CLN4A

Adult-onset neuronal ceroid lipofuscinosis, also known as Kufs disease, is a neurodegenerative disorder without retinal involvement. There are 2 overlapping phenotypes: type A, characterized by progressive myoclonic epilepsy, and type B, characterized by dementia and a variety of motor-system signs (summary by Arsov et al., 2011).In general, 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 (Mole et al., 2005). The ultrastructural pattern of lipopigment in CLN4 comprises a mixed pattern of 'granular,' 'curvilinear,' and 'fingerprint' profiles. (Mole et al., 2005).For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (OMIM ).

• Intellectual disability
• Seizures
• Ataxia
• Blindness
• Cerebellar atrophy

SOURCES: OMIM MENDELIAN

Low 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 jansky-bielschowsky disease|ceroid lipofuscinosis, neuronal, 2, variable age at onset

• Seizures
• Ataxia
• Delayed speech and language development
• Visual impairment
• Optic atrophy

SOURCES: OMIM MENDELIAN

Low match EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 16; EIEE16

Early infantile epileptic encephalopathy-16 is a severe autosomal recessive neurologic disorder characterized by onset of seizures in the first weeks or months of life. Seizures can be of various types, are unresponsive to medication, last for long periods of time, and occur frequently. Affected infants show psychomotor regression or lack of psychomotor development, as well as other neurologic features such as extrapyramidal signs and hypotonia. Most die in childhood (summary by Duru et al., 2010 and Milh et al., 2013).For a general phenotypic description and a discussion of genetic heterogeneity of EIEE, see EIEE1 (OMIM ).

• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly
• Optic atrophy

SOURCES: OMIM MENDELIAN