ABGC Neurology Disorders 2026

CADASIL - 3 Key Features

Stroke early signs: Migraines +Aura and Transient Ischemic Attacks (TIA's) (sudden temporary bouts of slurred speech/confusion, dizziness/blindness, facial drooping/numbness); Multiple Strokes; Cognitive Decline (Exec. Dysf. esp.) +Vascular Dementia

Canavan Disease - 3 Key Features

CNS Involvement +Seizures; The Triad: Macrocephaly, Hypotonia, Head Lag; Nystagmus

Holoprosencephaly - 3 Key Features

Incomplete division of the left and right hemispheres of the head; 4 main subtypes: Alobar: most severe form, cyclopia +/- proboscis, premaxillary agenesis (failed formation of upper jaw) +mid/bilat cleft lip, cebocephaly (single nostril nose); Semilobar: hypotelorism (close-spaced eyes), absent nasal septum +/- mid/bilat cleft lip/palate, flat nose; Lobar: hypotelorism (close-spaced eyes), Bilat cleft lip, flat nasal ridge; Middle Interhemispheric Fusion Variant (syntelencephaly): relatively normal facial appearance, hypotelorism, flat/narrow nasal bridge. Presents with CNS invovlement +seizures, Short Stature, Microcephaly > Macrocephaly/Hydrocephaly

Fragile X Syndrome - 3 Key Features

Males and sometimes Female Heterozygotes: CNS Involvement +Seizures +Autism, Distinct Craniofacial Features, Macroorchidism (big balls) in males; FXTAS in premutation males: Intention Tremor, Parkinsonism, Cognitive Decline; FXPOI in premutation females: Early menopause, irregular cycles, infertility

L1CAM-Associated Hydrocephalus (L1 Syndrome) - 3 Key Features

Male-exclusive. Wide phenotypic spectrum : severe HSAS -> moderate MASA -> mild corpus collosum agenesis: Hydrocephalus +CNS Involvement +Seizures, Adducted Thumbs (across palm), Spasticity (rigidity). No hydrocephalus for corpus callosum agenesis.

Tuberous Sclerosis (TSC) - 3 Key Features

Multisystem benign growths; 3 most common: Skin Findings (Hypomelanotic macules (ash leaf spots), "confetti" skin lesions, facial angiofibromas, etc.); CNS Involvement +Seizures +Autism (cortical tubers, subependymal giant cell astrocytoma (SEGA's), etc.); Kidney lesions (renal angiolipomas, etc.)

Neurofibromatosis 1 (NF1) - 3 Key Features

Skin Involvement (Cafe au Lait Macules, Cutaneous or Plexiform Neurofibromas); Optic Involvement (Choroidal abnormalities, Optic Nerve Gliomas, Lisch nodules); CNS Involvement +Seizures

Neurofibromatosis 2 (NF2-Related Schwannomatosis) - 3 Key Features

Ear Involvement (bilat. vestibular schwannomas, hearing loss, balance dysf.), Meningiomas (brain+spine membrane tumor), Eye Involvement (retinal hamartoma, cortical wedge cataract)

Rett Syndrome - 3 Key Features

Female Only; males present with different condition. Range from Classic, Variant, to mild learning delays. Normal development until 18 mo -> stagnation -> rapid regression @ 1-4y w/ hand stereotypies, CNS involvement +Seizures +Autism +Gait Ataxia, and Aquired Microcephaly, followed by long-term stagnation @ 5y

CADASIL - Brain Imaging and Lab Findings

MANY but big three : MRI: White Matter Hyperintensities esp. in Temporal Lobe, Lacunes (fluid-filled space), Global Brain Atrophy

CADASIL - Genetics and Inheritance

AD (it's in the name); NOTCH3

CADASIL - Onset and Progression

30-40y; 20-30y progression to severe dependency, higher risk pregnancies

CADASIL - Treatment

Standard stroke supportive care

Canavan Disease - Brain Imaging and Lab Findings

MRI: Leukodystrophy (symmetric white matter abn. signals) Labs: Elevated Urine NAA

Canavan Disease - Genetics and Inheritance

AR; ASPA

Canavan Disease - Onset and Progression

Typical: Infancy; Atypical: Childhood; Avg. Survival: 10y

Canavan Disease - Treatment

Palliative care; Multidisciplinary care

Holoprosencephaly - Brain Imaging and Lab Findings

MRI: Alobar: Monoventricle (no separation of cerebral hemispheres); Semilobar: Left and right frontal and parietal lobes are fused; Lobar: Left and Right frontal lobes are fused; MIHF (syntelencephaly): Left and Right Frontal and Parietal lobes are fused, with varying cleavage of the basal ganglia and thalami and varying presence of parts of the corpus calossum (Similar to semilobar with some varying fusion to the central parts of the brain)

Holoprosencephaly - Genetics and Inheritance

Reduced Penetrance AD or AR or XL or De Novo; Nonsyndromic : For single gene AD inheritance, more commonly from a heterozygous parent without presentation: 15% de novo SHH, 75% de novo ZIC2, 15% de novo SIX3, 30% de novo TGIF1 +many more; Syndromic : Single gene AR: STIL, DHCR7 (Smith-Lemli-Opitz) +more; Single gene XL: STAG2, SMC1A with FEMALE ONLY PRESENTATION (male lethal) and DE NOVO ONLY; Chromosomal: T13 (50% of cases), T18, Triploidy; Teratogenic: Maternal Diabetes +more.

Holoprosencephaly - Onset and Progression

At birth; Lifespan for Alobar HPE: up to 1y. Lifespan for other nonsyndromic HPE forms: childhood to full lifespan

Holoprosencephaly - Treatment

Reconstructive Surgery; Palliative and Multidisciplinary Care, Symptomatic treatment, PT, ST, OT, Mobility devices, feeding support

Fragile X Syndrome - Brain Imaging and Lab Findings

MRI: nothing distinct. Fragile X-Associated Tremor/Ataxia in premutation males: Hyperintensity on middle cerebellar peduncles (connection between cerebellum and brainstem)

Fragile X Syndrome - Onset and Progression

At birth; FXTAS: 50y; FXPOI: 40y. Normal life expectancy.

Fragile X Syndrome - Genetics and Inheritance

XL Dominant; FMR1 trinucleotide repeat expansion of CGG >200 = hypermethylation; Premutation: 55-200 repeats = unmethylated

Fragile X Syndrome - Treatment

Multidisciplinary Care, Symptomatic treatment, PT, ST, OT, reproductive counseling and HRT for females

L1CAM-Associated Hydrocephalus (L1 Syndrome) - Brain Imaging and Lab Findings

MRI: Elevated fluid volume and agenesis of corpus callosum +/- aqueduct of Sylvius stenosis (narrow)

L1CAM-Associated Hydrocephalus (L1 Syndrome) - Genetics and Inheritance

XL; L1CAM. Severe = truncating variants; Mild = missense variants

L1CAM-Associated Hydrocephalus (L1 Syndrome) - Onset and Progression

At birth for HSAS, Infancy for MASA, Childhood for Corpus Callosum Agenesis; Progression is stillbirth to normal lifespan depending on severity

L1CAM-Associated Hydrocephalus (L1 Syndrome) - Treatment

Shunting for hydrocephalus; multidisciplinary team.

Tuberous Sclerosis (TSC) - Brain Imaging and Lab Findings

MRI: condition-exclusive subependymal giant cell astrocytoma (SEGA) which can cause hydrocephalus; Labs: elevated serum creatinine means kidney problems

Tuberous Sclerosis (TSC) - Genetics and Inheritance

AD, 2/3 de novo; TSC2 and TSC1

Tuberous Sclerosis (TSC) - Onset and Progression

At birth or infancy; normal life expectancy

Tuberous Sclerosis (TSC) - Treatment

Derm exam, Full Body MRI, Echocardiogram, High Res Lung CT for females, Opthal exams, Corrective Surgery for findings. Higher risk for Renal Cell Carcinoma.

Neurofibromatosis 1 (NF1) - Brain Imaging and Lab Findings

MRI: Non-optic gliomas (asymptomatic and benign); Slit-Lamp of Eyes: Lisch Nodules

Neurofibromatosis 1 (NF1) - Genetics and Inheritance

AD, 1/2 de novo; NF1

Neurofibromatosis 1 (NF1) - Onset and Progression

Infancy; Slightly shorter than average lifespan

Neurofibromatosis 1 (NF1) - Treatment

Full body MRI, Opthal exams, Breast Cancer MRI at earlier age than pop., Surgical intervention and pain management when necessary.

Neurofibromatosis 2 (NF2-Related Schwannomatosis) - Brain Imaging and Lab Findings

MRI: Meningiomas

Neurofibromatosis 2 (NF2-Related Schwannomatosis) - Genetics and Inheritance

AD, 1/2 de novo; NF2

Neurofibromatosis 2 (NF2-Related Schwannomatosis) - Onset and Progression

Previously believed to be an adult-onset condition; now understood to have presentation in childhood; reduced lifespan to 40y

Neurofibromatosis 2 (NF2-Related Schwannomatosis) - Treatment

Brain MRI, Opthal exams, Audio exams, Surgical intervention when necessary

Rett Syndrome - Brain Imaging and Lab Findings

MRI: Global atrophy, particularly in the cerebellum and frontal cortex, normal signal intensity (rules out structural malform. and demyelination)

Rett Syndrome - Genetics and Inheritance

XL Dominant 99% de novo (only in women, males have a different condition); MECP2

Rett Syndrome - Onset and Progression

Infancy (6-18 mo); Reduced lifespan, live until middle ages

Rett Syndrome - Treatment

Multidisciplinary and symptom-based treatment only