MedGen

Classic Joubert syndrome (JS) is characterized by three primary findings: A distinctive cerebellar and brain stem malformation called the molar tooth sign (MTS). Hypotonia. Developmental delays. Often these findings are accompanied by episodic tachypnea or apnea and/or atypical eye movements. In general, the breathing abnormalities improve with age, truncal ataxia develops over time, and acquisition of gross motor milestones is delayed. Cognitive abilities are variable, ranging from severe intellectual disability to normal. Additional findings can include retinal dystrophy, renal disease, ocular colobomas, occipital encephalocele, hepatic fibrosis, polydactyly, oral hamartomas, and endocrine abnormalities. Both intra- and interfamilial variation are seen. [from GeneReviews]

Developmental and epileptic encephalopathy-8 (DEE8) is an X-linked disorder characterized by seizure onset before 2 years of age and severe developmental delay. Some patients have hyperekplexia (summary by Shimojima et al., 2011). For general phenotypic descriptions and discussions of genetic heterogeneity of developmental and epileptic encephalopathy and hyperekplexia, see DEE1 (308350) and HKPX1 (149400), respectively. [from OMIM]

Complex cortical dysplasia with other brain malformations-13 (CDCBM13) is an autosomal dominant neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development. Brain imaging shows variable neuronal migration defects resulting in cortical malformations, including pachygyria. More variable features include early-onset seizures and dysmorphic features. Some patients may also show signs of peripheral neuropathy, such as abnormal gait, hyporeflexia, and foot deformities (summary by Willemsen et al., 2012 and Poirier et al., 2013). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039). [from OMIM]

Complex cortical dysplasia with other brain malformations-14A (CDCBM14A) is an autosomal recessive neurologic disorder characterized by global developmental delay with impaired intellectual development, motor delay, poor speech development, and early-onset seizures, often focal or atypical absence. Additional features may include strabismus, nystagmus, exo- or esotropia, axial hypotonia, and spasticity. Brain imaging shows bilateral frontoparietal polymicrogyria, a frontal-predominant cobblestone malformation of the cortex, scalloping of the cortical/white matter junction, enlarged ventricles, and hypoplasia of the pons, brainstem, and cerebellum. The disorder can be classified as a malformation of cortical development (summary by Parrini et al., 2009; Luo et al., 2011; Zulfiqar et al., 2021). For a discussion of genetic heterogeneity of CDCBM, see CDCBM1 (614039). [from OMIM]

Complex cortical dysplasia with other brain malformations (CDCBM) is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved (summary by Poirier et al., 2010). Genetic Heterogeneity of Complex Cortical Dysplasia with Other Brain Malformations See also CDCBM2 (615282), caused by mutation in the KIF5C gene (604593) on chromosome 2q23; CDCBM3 (615411), caused by mutation in the KIF2A gene (602591) on chromosome 5q12; CDCBM4 (615412), caused by mutation in the TUBG1 gene (191135) on chromosome 17q21; CDCBM5 (615763), caused by mutation in the TUBB2A gene (615101) on chromosome 6p25; CDCBM6 (615771), caused by mutation in the TUBB gene (191130) on chromosome 6p21; CDCBM7 (610031), caused by mutation in the TUBB2B gene (612850) on chromosome 6p25; CDCBM9 (618174), caused by mutation in the CTNNA2 gene (114025) on chromosome 2p12; CDCBM10 (618677), caused by mutation in the APC2 gene (612034) on chromosome 19p13; CDCBM11 (620156), caused by mutation in the KIF26A gene (613231) on chromosome 14q32; CDCBM12 (620316), caused by mutation in the CAMSAP1 gene (613774) on chromosome 9q34; CDCBM13 (614563), caused by mutation in the DYNC1H1 gene (600112) on chromosome 14q32; CDCBM14A (606854) and CDCBM14B (615752), caused by mutation in the ADGRG1 gene (604110) on chromosome 16q21; and CDCBM15 (618737), caused by mutation in the TUBGCP2 gene (617817) on chromosome 10q26. The designation CDCBM8 was previously used to represent a phenotype caused by mutation in the TUBA8 gene (see 605742.0001) on chromosome 22q11; the patients with this phenotype were subsequently found to have a homozygous mutation in the SNAP29 gene (604202.0002), also on chromosome 22q11, that may have been responsible for the disorder. The same mutation in SNAP29 causes a similar disorder, CEDNIK syndrome (609528). See also lissencephaly (e.g., LIS1, 607432), which shows overlapping features and may result from mutation in tubulin genes. [from OMIM]

A rare mitochondrial oxidative phosphorylation disorder with characteristics of neonatal onset of hypotonia, feeding difficulties, deafness, and early fatal respiratory failure. Cardiac and liver involvement has been reported. Serum lactate is increased and metabolic studies show decreased activity of mitochondrial respiratory complexes I and IV in skeletal muscle. [from SNOMEDCT_US]

Neurodevelopmental disorder with seizures, microcephaly, and brain abnormalities (NEDSMBA) is an autosomal recessive disorder characterized by a core phenotype of moderate to profound developmental delay, progressive microcephaly, epilepsy, and periventricular calcifications (summary by Rosenhahn et al., 2022). [from OMIM]

A type of polymicrogyria with a gradient of severity (anterior more severe than posterior) extending from frontal poles posteriorly to precentral gyrus and inferiorly to frontal operculum. [from HPO]