MedGen

Familial hemiplegic migraine (FHM) falls within the category of migraine with aura. In migraine with aura (including FHM) the neurologic symptoms of aura are unequivocally localizable to the cerebral cortex or brain stem and include visual disturbance (most common), sensory loss (e.g., numbness or paresthesias of the face or an extremity), and dysphasia (difficulty with speech). FHM must include motor involvement, such as hemiparesis (weakness of an extremity). Hemiparesis occurs with at least one other symptom during FHM aura. Neurologic deficits with FHM attacks can be prolonged for hours to days and may outlast the associated migrainous headache. FHM is often earlier in onset than typical migraine, frequently beginning in the first or second decade; the frequency of attacks tends to decrease with age. Approximately 40%-50% of families with CACNA1A-FHM have cerebellar signs ranging from nystagmus to progressive, usually late-onset mild ataxia. [from GeneReviews]

C9orf72 frontotemporal dementia and/or amyotrophic lateral sclerosis (C9orf72-FTD/ALS) is characterized most often by frontotemporal dementia (FTD) and upper and lower motor neuron disease (MND); however, atypical presentations also occur. Age at onset is usually between 50 and 64 years (range: 20-91 years) irrespective of the presenting manifestations, which may be pure FTD, pure amyotrophic lateral sclerosis (ALS), or a combination of the two phenotypes. The clinical presentation is highly heterogeneous and may differ between and within families, causing an unpredictable pattern and age of onset of clinical manifestations. The presence of MND correlates with an earlier age of onset and a worse overall prognosis. [from GeneReviews]

CHMP2B frontotemporal dementia (CHMP2B-FTD) has been described in a single family from Denmark, in one individual with familial FTD from Belgium, and in one individual with FTD and no family history. It typically starts between ages 46 and 65 years with subtle personality changes and slowly progressive behavioral changes, dysexecutive syndrome, dyscalculia, and language disturbances. Disinhibition or loss of initiative is the most common presenting symptom. The disease progresses over a few years into profound dementia with extrapyramidal symptoms and mutism. Several individuals have developed an asymmetric akinetic rigid syndrome with arm and gait dystonia and pyramidal signs that may be related to treatment with neuroleptic drugs. Symptoms and disease course are highly variable. Disease duration may be as short as three years or longer than 20 years. [from GeneReviews]

Spinocerebellar ataxia-29 (SCA29) is an autosomal dominant neurologic disorder characterized by onset in infancy of delayed motor development and mild cognitive delay. Affected individuals develop a very slowly progressive or nonprogressive gait and limb ataxia associated with cerebellar atrophy on brain imaging. Additional variable features include nystagmus, dysarthria, and tremor (summary by Huang et al., 2012). For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (164400). [from OMIM]

Frontotemporal dementia and/or amyotrophic lateral sclerosis-8 (FTDALS8) is an autosomal dominant neurodegenerative disorder characterized by adult-onset dementia manifest as memory impairment, executive dysfunction, and behavioral or personality changes. Some patients may develop ALS or parkinsonism. Neuropathologic studies show frontotemporal lobar degeneration (FTLD) with tau (MAPT; 157140)- and TDP43 (605078)-immunoreactive inclusions (summary by Dobson-Stone et al., 2020). For a discussion of genetic heterogeneity of FTDALS, see FTDALS1 (105550). [from OMIM]

Periventricular nodular heterotopia-9 (PVNH9) is an autosomal dominant neurologic disorder characterized as a malformation of cortical development. Anterior predominant PVNH, thin corpus callosum, and decreased white matter volume are found on brain imaging, but the clinical effects are variable. Most patients have impaired intellectual development and cognitive defects associated with low IQ (range 50 to 80), learning disabilities, and behavior abnormalities. Some patients develop seizures that tend to have a focal origin. However, some mutation carriers may be less severely affected with borderline or even normal IQ, suggesting incomplete penetrance of the phenotype (summary by Heinzen et al., 2018, Walters et al., 2018). For a discussion of genetic heterogeneity of periventricular nodular heterotopia, see 300049. [from OMIM]

A specific learning disability involving mathematics and arithmetic. [from HPO]