IllnessPrenatally abnormal corpus callosum, differential diagnosis

NGS +

[Sanger]

Abnormalities of the corpus callosum (ACC) are common malformations of the brain and usually diagnosed after the 20th week of gestation. Fetuses with isolated ACC have a better prognosis than those with additional abnormalities. Yet, the unpredictable neurodevelopmental outcomes of isolated ACC make prenatal counseling particularly challenging. ACC are heterogeneous disorders that can occur as manifestations in the context of >200 genetic syndromes and, in particular, are also observed in association with major malformations of the embryonic forebrain. The most common postnatal findings in patients with ACC include mental retardation, visual disturbances, speech delay, and seizures. Even in cases without developmental delay and normal intelligence, mild behavioral or social problems and ADHD have been described. Genetic factors are very common. Among genetic causes, a "syndromic diagnosis" is made in 30-45% of cases, and a monogenic cause can be identified in 20-35%. The numerous genetic causes of ACC are based on autosomal dominant, autosomal recessive, and X-linked inheritance. A negative molecular genetic result does not constitute exclusion of the clinical diagnosis.

Reference: https://www.sciencedirect.com/science/article/pii/B9780323371018000333?via%3Dihub

• Agenesis of the corpus callosum with peripheral neuropathy (SLC12A6)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2O (DYNC1H1)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2X (SPG11)
• Allelic: Metachondromatosis (PTPN11)
• Allelic: Neuropathy, hereditary sensory, type IIC (KIF1A)
• Allelic: Rigidity + multifocal seizure syndrome, lethal neonatal (BRAT1)
• Allelic: Spastic paraplegia 30, AD (KIF1A)
• Allelic: Spastic paraplegia 30, AR (KIF1A)
• Allelic: Spinal muscular atrophy, lower extremity-predominant 1, AD (DYNC1H1)
• Amyotrophic lateral sclerosis 5, juvenile (SPG11)
• Aniridia (PAX6)
• Anterior segment dysgenesis 5, multiple subtypes (PAX6)
• Aqueductal stenosis [panelapp] (SMARCC1)
• Bainbridge-Ropers syndrome (ASXL3)
• Basal cell nevus syndrome (PTCH1)
• Blepharophimosis-impaired intellectual development syndrome (SMARCA2)
• CRASH syndrome (L1CAM)
• Cataract with late-onset corneal dystrophy (PAX6)
• Coffin-Siris syndrome 1 (ARID1B)
• Coffin-Siris syndrome 2 (ARID1A)
• Coffin-Siris syndrome 3 (SMARCB1)
• Coffin-Siris syndrome 4 (SMARCA4)
• Coffin-Siris syndrome 5 (SMARCE1)
• Coloboma of optic nerve (PAX6)
• Coloboma, ocular (PAX6)
• Congenital hydrocephalus [panelapp] (SMARCC1)
• Corpus callosum abnormalities [panelapp] (SMARCC1)
• Corpus callosum, agenesis of, with facial anomalies, cerebellar ataxia (FRMD4A)
• Corpus callosum, partial agenesis of (L1CAM)
• Cortical dysplasia, complex, with other brain malformations 5 (TUBB2A)
• Cortical dysplasia, complex, with other brain malformations 6 ITUBB)
• Cortical dysplasia, complex, with other brain malformations 7 (TUBB2B)
• Culler-Jones syndrome (GLI2)
• Developmental + epileptic encephalopathy 1 (ARX)
• Donnai-Barrow syndrome (LRP2)
• Encephalopathy, progressive, early-onset, brain atrophy, thin corpus callosum (TBCD)
• Epilepsy, familial temporal lobe, 7 (RELN)
• Foveal hypoplasia 1 (PAX6)
• Glycine encephalopathy (GLDC)
• Hardikar syndrome (MED12)
• Holoprosencephaly 11 (CDON)
• Holoprosencephaly 2 (SIX3)
• Holoprosencephaly 3 (SHH)
• Holoprosencephaly 4 (TGIF1)
• Holoprosencephaly 5 (ZIC2)
• Holoprosencephaly 7 (PTCH1)
• Holoprosencephaly 9 (GLI2)
• Hydranencephaly with abnormal genitalia (ARX)
• Hydrocephalus due to aqueductal stenosis (L1CAM)
• Hydrocephalus with Hirschsprung disease (L1CAM)
• Hydrocephalus with congenital idiopathic intestinal pseudoobstruction (L1CAM)
• Hypogonadotropic hypogonadism 1 with/-out anosmia, Kallmann syndrome 1 (ANOS1)
• Intellectual developmental disorder with dysmorphic facies + ptosis (BRPF1)
• Intellectual developmental disorder, AD 13 (DYNC1H1)
• Intellectual developmental disorder, AD 36 (PPPR1A)
• Intellectual developmental disorder, XL 29 (ARX)
• Intellectual developmental disorder, XL syndromic 14 (UPFB)
• Intellectual developmental disorder, XL syndromic, Stocco dos Santos type (SHROOM4)
• Keratitis (PAX6)
• Koolen-De Vries syndrome (KANSL1)
• LEOPARD syndrome 1 (PTPN11)
• Linear skin defects with multiple congenital anomalies 1 (HCCS)
• Lissencephaly 1 (PAFAH1B1)
• Lissencephaly 2, Norman-Roberts type (RELN)
• Lissencephaly 3 (TUBA1A)
• Lissencephaly 4, with microcephaly (NDE1)
• Lissencephaly, XL (DCX)
• Lissencephaly, XL 2 (ARX)
• Lujan-Fryns syndrome (MED12)
• MASA syndrome (L1CAM)
• Macrothrombocytopenia, isolated, 2, AD (TUBA8)
• Martsolf syndrome 1 (RAB3GAP2)
• Martsolf syndrome 2 (RAB3GAP1)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2 (AKT3)
• Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 3 (CCND2)
• Meningioma, familial, susceptibility to (SMARCE1)
• Microcephaly, short stature + polymicrogyria with seizures (RTTN)
• Microhydranencephaly (NDE1)
• Microphthalmia with coloboma 5 (SHH)
• Morning glory disc anomaly (PAX6)
• Mowat-Wilson syndrome (ZEB2)
• NESCAV syndrome (KIF1A)
• Neurodevelopmental disorder with cerebellar atrophy with/-out seizures (BRAT1)
• Nicolaides-Baraitser syndrome (SMARCA2)
• Noonan syndrome 1 (PTPN11)
• Ohdo syndrome, XL (MED12)
• Opitz GBBB syndrome (MID1)
• Opitz-Kaveggia syndrome (MED12)
• Optic nerve hypoplasia (PAX6)
• Partington syndrome (ARX)
• Prenatally unusual structure of the corpus callosum
• Primrose syndrome (ZBTB20)
• Proud syndrome (ARX)
• Rett syndrome, congenital variant (FOXG1)
• Rhabdoid tumor predisposition syndrome 1 (SMARCB1)
• Rhabdoid tumor predisposition syndrome 2 (SMARCA4)
• Schizencephaly (SHH)
• Schizencephaly (SIX3)
• Schwannomatosis-1, susceptibility to (SMARCB1)
• Septal agenesis [panelapp] (SMARCC1)
• Single median maxillary central incisor (SHH)
• Spastic paraplegia 11, AR (SPG11)
• Subcortical laminal heterotopia, XL (DCX)
• Subcortical laminar heterotopia (PAFAH1B1)
• Symmetric circumferential skin creases, congenital, 1 ITUBB)
• Vici syndrome (EPG5)
• Warburg micro syndrome 1 (RAB3GAP1)
• Warburg micro syndrome 2 (RAB3GAP2)
• Warburg micro syndrome 3 (RAB18)
• Weiss-Kruszka syndrome (ZNF462)