Ataxia, and Macrocephaly

Low match MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS 2B, REMITTING, WITH OR WITHOUT MENTAL RETARDATION; MLC2B

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

Low match MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS 2A; MLC2A

Megalencephalic leukoencephalopathy with subcortical cysts-2A is an autosomal recessive neurodegenerative disorder characterized by infantile-onset macrocephaly and later onset of motor deterioration, with ataxia and spasticity, seizures, and cognitive decline of variable severity. Brain MRI shows typical white matter abnormalities, including swelling of the cerebral white matter and subcortical cysts, in all stages of the disease (summary by Lopez-Hernandez et al., 2011).Heterozygous mutations in the HEPACAM gene can cause a similar, but less severe disorder that shows improvement of MRI changes with age (MLC2B ).

• Intellectual disability
• Seizures
• Ataxia
• Spasticity
• Motor delay

SOURCES: OMIM MENDELIAN

Low match MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a form of leukodystrophy that is characterized by infantile-onset macrocephaly, often with mild neurologic signs at presentation (such as mild motor delay), which worsen with time, leading to poor ambulation, falls, ataxia, spasticity, increasing seizures and cognitive decline. Brain magnetic resonance imaging reveals diffusely abnormal and mildly swollen white matter as well as subcortical cysts in the anterior temporal and frontoparietal regions.

MEGALENCEPHALIC LEUKOENCEPHALOPATHY WITH SUBCORTICAL CYSTS Is also known as mlc|megalencephaly-cystic leukodystrophy syndrome|van der knaap disease|vl|vacuolating megalencephalic leukoencephalopathy with subcortical cysts|van der knaap syndrome|lvm|megalencephalic leukodystrophy|leukoencephalopathy with swelling and cysts

• Seizures
• Ataxia
• Spasticity
• Delayed speech and language development
• Motor delay

SOURCES: OMIM ORPHANET MENDELIAN

Low match N-ACETYLASPARTATE DEFICIENCY; NACED

N-ACETYLASPARTATE DEFICIENCY; NACED Is also known as naa deficiency|hypoacetylaspartia

• Seizures
• Global developmental delay
• Short stature
• Generalized hypotonia
• Microcephaly

SOURCES: OMIM MENDELIAN

Low match JOUBERT SYNDROME 32; JBTS32

JBTS32 is an autosomal recessive developmental disorder characterized by delayed psychomotor development, intellectual disability, dysmorphic facial features, and postaxial polydactyly. Brain imaging shows cerebellar abnormalities consistent with the molar tooth sign (MTS) (summary by De Mori et al., 2017).For discussion of genetic heterogeneity of Joubert syndrome, see JBTS1 (OMIM ).

• Intellectual disability
• Seizures
• Global developmental delay
• Ataxia
• Hypertelorism

SOURCES: OMIM MENDELIAN

Low match ATYPICAL TERATOID RHABDOID TUMOR

Atypical teratoid rhabdoid tumor (ATRT) is a highly malignant central nervous system (CNS) rhabdoid tumor (RT; see this term) found almost exclusively in children.

ATYPICAL TERATOID RHABDOID TUMOR Is also known as atrt

• Seizures
• Ataxia
• Muscle weakness
• Macrocephaly
• Hydrocephalus

SOURCES: ORPHANET MENDELIAN

Low match SCLEROSTEOSIS 2; SOST2

Sclerosteosis is a severe sclerosing bone dysplasia characterized by progressive skeletal overgrowth. Syndactyly is a variable manifestation. The disorder is rare and the majority of affected individuals have been reported in the Afrikaner population of South Africa (summary by Brunkow et al., 2001).For a discussion of genetic heterogeneity of sclerosteosis, see SOST1 (OMIM ).

• Hearing impairment
• Hypertelorism
• Macrocephaly
• Gait disturbance
• Frontal bossing

SOURCES: OMIM MENDELIAN

Low match OPTIC ATROPHY 11; OPA11

OPA11 is an autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, ataxia, optic atrophy, and leukoencephalopathy on brain imaging. Laboratory studies are consistent with mitochondrial dysfunction (summary by Hartmann et al., 2016).For a discussion of genetic heterogeneity of optic atrophy, see OPA1 (OMIM ).

• Intellectual disability
• Global developmental delay
• Short stature
• Generalized hypotonia
• Hearing impairment

SOURCES: OMIM MENDELIAN

Low match EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 31; EIEE31

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

SOURCES: OMIM MENDELIAN

Low match LHERMITTE-DUCLOS DISEASE

Lhermitte-Duclos disease (LDD) is a very rare disorder characterized by abnormal development and enlargement of the cerebellum, and an increased intracranial pressure.

LHERMITTE-DUCLOS DISEASE Is also known as dysplastic gangliocytoma of the cerebellum|ldd

• Seizures
• Ataxia
• Macrocephaly
• Hydrocephalus
• Headache

SOURCES: ORPHANET MENDELIAN