Intellectual disability, and Abnormality of the cerebral white matter

Autosomal recessive spastic paraplegia type 59 is a very rare, complex hereditary spastic paraplegia characterized by an early onset of progressive lower limb spasticity, tip-toe walking, scissor gait, hyperreflexia and clonus that may be associated with borderline intellectual disability. Nystagmus and pes equinovarus have also been reported.

AUTOSOMAL RECESSIVE SPASTIC PARAPLEGIA TYPE 59 Is also known as spg59

• Intellectual disability
• Nystagmus
• Talipes equinovarus
• Spastic paraplegia
• Abnormality of the cerebral white matter

SOURCES: ORPHANET MENDELIAN

Hypomyelinating leukodystrophy-11 is an autosomal recessive neurologic disorder characterized by delayed psychomotor development and other neurologic features associated with hypomyelination on brain imaging. Some patients may have additional nonneurologic features, particularly dental abnormalities and possibly hypogonadotropic hypogonadism (summary by Thiffault et al., 2015).For a general phenotypic description and a discussion of genetic heterogeneity of HLD, see {312080}.

• Intellectual disability
• Global developmental delay
• Ataxia
• Spasticity
• Myopia

SOURCES: OMIM MENDELIAN

• Intellectual disability
• Microcephaly

SOURCES: OMIM MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Microcephaly

SOURCES: OMIM MENDELIAN

Dihydropteridine reductase (DHPR) deficiency is a severe form of hyperphenylalaninemia (HPA) due to impaired regeneration of tetrahydrobiopterin (BH4) (see this term), leading to decreased levels of neurotransmitters (dopamine, serotonin) and folate in cerebrospinal fluid, and causing neurological symptoms such as psychomotor delay, hypotonia, seizures, abnormal movements, hypersalivation, and swallowing difficulties.

DIHYDROPTERIDINE REDUCTASE DEFICIENCY Is also known as hyperphenylalaninemia due to dihydropteridine reductase deficiency|pku type 2|phenylketonuria type 2

• Intellectual disability
• Global developmental delay
• Microcephaly
• Dysphagia

SOURCES: ORPHANET MENDELIAN

Mirror movements are contralateral involuntary movements that mirror voluntary ones. Whereas mirror movements are occasionally found in normal young children, persistence beyond the age of 10 years is abnormal. Congenital mirror movements tend to persist throughout adulthood and tend to occur more commonly in the upper extremities (summary by Sharafaddinzadeh et al., 2008 and Srour et al., 2010). Some patients with DCC mutations have agenesis of the corpus callosum (Marsh et al., 2017). Genetic Heterogeneity of Mirror MovementsSee also MRMV2 (OMIM ), caused by mutation in the RAD51 gene (OMIM ) on chromosome 15q15, and MRMV3 (OMIM ), caused by mutation in the DNAL4 gene (OMIM ) on chromosome 22q13.

MIRROR MOVEMENTS 1; MRMV1 Is also known as mirror movements 1 and/or agenesis of the corpus callosum|bimanual synergia|mirror movements, congenital

• Pain
• Delayed speech and language development
• Intellectual disability, mild
• Agenesis of corpus callosum
• Abnormality of the nervous system

SOURCES: OMIM MENDELIAN

Cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ) is a genetically heterogeneous disorder characterized by congenital cerebellar ataxia and mental retardation (summary by Gulsuner et al., 2011).For a discussion of genetic heterogeneity of CAMRQ, see CAMRQ1 (OMIM ).

CEREBELLAR ATAXIA, MENTAL RETARDATION, AND DYSEQUILIBRIUM SYNDROME 4; CAMRQ4 Is also known as cerebellar ataxia and mental retardation with or without quadrupedal locomotion 4

• Intellectual disability
• Ataxia
• Dysarthria
• Cerebellar atrophy
• Cerebral atrophy

SOURCES: OMIM MENDELIAN

Focal cortical dysplasia type II (FCORD2), or focal cortical dysplasia of Taylor (FCDT), is a cerebral developmental malformation that results in a clinical phenotype of intractable epilepsy, usually requiring surgery. FCORD2 has been classified histologically into 2 subtypes: a type without balloon cells, known as type IIA, and a type with balloon cells, known as type IIB (Palmini et al., 2004). Affected individuals have refractory seizures, usually with onset in early childhood, and may have persistent intellectual disability. Most patients require neurosurgical resection of affected brain tissue to ameliorate seizure frequency and severity (summary by Moller et al., 2016).

FOCAL CORTICAL DYSPLASIA, TYPE II; FCORD2 Is also known as focal cortical dysplasia of taylor|cortical dysplasia of taylor|cdt|fcdt|fcd2

• Intellectual disability
• Seizures
• Cognitive impairment
• Intellectual disability, severe
• EEG abnormality

SOURCES: ORPHANET OMIM MENDELIAN

Autosomal dominant remitting MLC2B is characterized by infantile-onset of macrocephaly and mildly delayed motor development associated with white matter abnormalities on brain MRI that improve with age. As children, some patients have mild residual hypotonia or clumsiness, but otherwise have no residual motor abnormalities. About 40% of patients have mental retardation (summary by van der Knaap et al., 2010 and Lopez-Hernandez et al., 2011).Homozygous or compound heterozygous mutations in the HEPACAM gene can cause a more severe and progressive disorder associated with ataxia, spasticity, and mental retardation (MLC2A ).For a discussion of genetic heterogeneity of megalencephalic leukoencephalopathy with subcortical cysts, see MLC1 (OMIM ).

• Intellectual disability
• Generalized hypotonia
• Ataxia
• Spasticity
• Motor delay

SOURCES: OMIM MENDELIAN

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Delayed speech and language development

SOURCES: OMIM MENDELIAN