Klinische FragestellungMentale Retardierung bei Mikrozephalie, Differentialdiagnose

NGS +

Bei Mikrozephalie liegen oft auch gleichzeitig Epilepsie (40%), Augenleiden (20-50%), Zerebralparese (20%) und namentlich mentale Retardierung (50%) verschiedenen Ausmaßes vor. Bei der mentaler Retardierung kombiniert mit Mikrozephalie werden alle klassischen Erbgänge beobachtet, und multifaktorielle Geschehen stehen im Vordergrund. Die Diagnoserate ist vordringlich von der Qualität und den Ergebnissen der klinischen Voruntersuchungen abhängig. Ein unauffälliger genetischer Befund bedeutet keinen Ausschluss der klinischen Verdachtsdiagnose.

Referenz: https://www.aan.com/PressRoom/home/GetDigitalAsset/8479

• Alias: Intellectual disability + microcephaly
• Alias: Psycho-motor retardation + microcephaly
• Allelic: Autism, susceptibility to, XL 5 (RPL10)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2N (AARS1)
• Allelic: Charcot-Marie-Tooth disease, axonal, type 2Z (MORC2)
• Allelic: Cutaneous telangiectasia + cancer syndrome, familial (ATR)
• Allelic: DNA damage repair defect [panelapp] (ZNF668)
• Allelic: Exudative vitreoretinopathy 7 (CTNNB1)
• Allelic: Hypogonadotropic hypogonadism 14 with/-out anosmia (WDR11)
• Allelic: Lung cancer, susceptibility to (ERCC6)
• Allelic: Macular degeneration, age-related, susceptibility to, 5 (ERCC6)
• Allelic: Meckel syndrome 12 (KIF14)
• Allelic: Microhydranencephaly (NDE1)
• Allelic: Migraine, familial basilar (ATP1A2)
• Allelic: Migraine, familial hemiplegic, 2 (ATP1A2)
• Allelic: Multiple myeloma, resistance to (LIG4)
• Allelic: Neonatal cholestatic liver disease [panelapp] (VPS50)
• Allelic: Premature chromatid separation trait (BUB1B)
• Allelic: Premature ovarian failure 11 (ERCC6)
• Allelic: Spastic paraplegia 83, AR (HPDL)
• Allelic: Spinocerebellar ataxia, AR 24 (UBA5)
• Allelic: Thyroid carcinoma, follicular (MINPP1)
• Allelic: UV-sensitive syndrome 1 (ERCC6)
• Allelic: UV-sensitive syndrome 2 (ERCC8)
• Aicardi-Goutieres syndrome 2 (RNASEH2B)
• Alazami syndrome (LARP7)
• Alpha-thalassemia/mental retardation syndrome (ATRX)
• Alternating hemiplegia of childhood 1 (ATP1A2)
• Alzahrani-Kuwahara syndrome (SMG8)
• Asparagine synthetase deficiency (ASNS)
• Baralle-Macken syndrome (COPB1)
• Basel-Vanagait-Smirin-Yosef syndrome (MED25)
• Bloom syndrome (BLM)
• Brain malformation, facial dysmorphism [panelapp] (ZNF668)
• Cerebrooculofacioskeletal syndrome 1 (ERCC6)
• Cleft palate, cardiac defects, and mental retardation (MEIS2)
• Cockayne syndrome, type A (ERCC8)
• Cockayne syndrome, type B (ERCC6)
• Congenital disorder of glycosylation, type Ie (DPM1)
• Cornelia de Lange syndrome 1 (NIPBL)
• Cornelia de Lange syndrome 2 (SMC1A)
• Cornelia de Lange syndrome 3 (SMC3)
• Cornelia de Lange syndrome 4 (RAD21)
• Cornelia de Lange syndrome 5 (HDAC8)
• De Sanctis-Cacchione syndrome (ERCC6)
• Developmental + epileptic encephalopathy 29 (AARS1)
• Developmental + epileptic encephalopathy 44 (UBA5)
• Developmental + epileptic encephalopathy 64 (RHOBTB2)
• Developmental + epileptic encephalopathy 83 (UGP2)
• Developmental + epileptic encephalopathy 85, with/-out midline brain defects (SMC1A)
• Developmental + epileptic encephalopathy 98 (ATP1A2)
• Developmental delay with/-out dysmorphic facies + autism (TRRAP)
• Developmental delay, AR, intellectual disability + microcephaly (NAA20)
• Developmental delay, impaired growth, dysmorphic facies, axonal neuropathy (MORC2)
• Diencephalic-mesencephalic junction dysplasia syndrome 1 (PCDH12)
• Encephalopathy, progressive, early-onset, with brain atrophy + spasticity (TRAPPC12)
• Encephalopathy, progressive, early-onset, with brain atrophy + thin corpus callosum (TBCD)
• Epilepsy, intellectual disability, microcephaly [panelapp] (ATP6V0C)
• FG syndrome 4 (CASK)
• Failure to thrive, profound global developmental delay, postnatal microcephaly [panelapp] (VPS50)
• Fanconi anemia, complementation group P (SLX4)
• Faundes-Banka syndrome (EIF5A)
• Feingold syndrome 1 (MYCN)
• Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria + dysmorphic facies (ATP1A2)
• Filippi syndrome (CKAP2L)
• Galloway-Mowat syndrome 1 (WDR73)
• Galloway-Mowat syndrome 3 (OSGEP)
• Galloway-Mowat syndrome 6 (WDR4)
• Global developm. delay, intell. disability, seizures, microcephaly, short digit [no OMIM] (HNRNPR)
• Glycine encephalopathy with normal serum glycine (SLC6A9)
• Goldberg-Shprintzen megacolon syndrome (KIFBP)
• Growth delay, microcephaly + intellectual disability [panelapp] (HIST1H4C)
• Growth retardation with deafness + mental retardation due to IGF1 deficiency (IGF1)
• Growth retardation, impaired intellectual development, hypotonia + hepatopathy (IARS1)
• Growth retardation, intellectual developmental disorder, hypotonia + hepatopathy (IARS)
• Heyn-Sproul-Jackson syndrome (DNMT3A)
• Holoprosencephaly 13, XL (STAG2)
• Hypotonia, infantile, with psychomotor retardation + characteristic facies 2 (UNC80)
• ID [MONDO:0001071], microcephaly [MONDO:0001149], short stature [HP:0004322] (WDR11)
• ID [panelapp] (CTCF)
• ID, microcephaly, cataracts, epilepsy, hypertonia, dystonia [panelapp] (ZNF526)
• ID, microcephaly, heart defect, cleft palate, contract., deafness, skin creases [panelapp] (FBRSL1)
• ID, postnatal microcephaly, failure to thrive, abnormal abdomen [panelapp] (ATP9A)
• ID, postnatal microcephaly, hypotonia, failure to thrive [panelapp] (SMARCA5)
• Insulin-like growth factor I, resistance to (IGF1R)
• Intellectual developmental disorder with abnormal behavior, microcephaly + short stature (PUS7)
• Intellectual developmental disorder with hypotonia, impaired speech, dysmorphic facies (TNPO2)
• Intellectual developmental disorder, AD 44, with microcephaly (TRIO)
• Intellectual developmental disorder, AR 72 (METTL5)
• Intellectual developmental disorder, XL syndromic, Christianson type (SLC9A6)
• Intellectual developmental disorder, XL, syndromic, 35 (RPL10)
• Jawad syndrome (RBBP8)
• Kaya-Barakat-Masson syndrome (YIF1B)
• LIG4 syndrome (LIG4)
• Leukodystrophy, adult-onset, AD (LMNB1)
• Leukodystrophy, hypomyelinating, 10 (PYCR2)
• Leukodystrophy, hypomyelinating, 14 (UFM1)
• Lissencephaly 4 [with microcephaly] (NDE1)
• MEHMO syndrome (EIF2S3)
• Mandibulofacial dysostosis, Guion-Almeida type (EFTUD2)
• Martsolf syndrome 2 (RAB3GAP1)
• Mega-corpus-callosum syndrome with cerebellar hypoplasia + cortical malformations (MAST1)
• Meier-Gorlin syndrome, microcephaly, intellectual disability [panelapp] (MCM7)
• Menke-Hennekam syndrome 1 (CREBBP)
• Mental retardation, AD 33 (DPP6)
• Mental retardation, AD 40 (CHAMP1)
• Mental retardation, AD 54 (CAMK2B)
• Mental retardation, AD 7 (DYRK1A)
• Mental retardation, AR 13 (TRAPPC9)
• Mental retardation, AR 60 (TAF13)
• Mental retardation, microcephaly with pontine + cerebellar hypoplasia (CASK)
• Mental retardation, with/-out nystagmus (CASK)
• Mental retardation-hypotonic facies syndrome, XL (ATRX)
• Microcephalic osteodysplastic primordial dwarfism, type II (PCNT)
• Microcephaly + chorioretinopathy, AR, 1 (TUBGCP6)
• Microcephaly + chorioretinopathy, AR, 2 (PLK4)
• Microcephaly 1, primary, AR (MCPH1)
• Microcephaly 10, primary, AR (ZNF335)
• Microcephaly 11, primary, AR (PHC1)
• Microcephaly 12, primary, AR (CDK6)
• Microcephaly 13, primary, AR (CENPE)
• Microcephaly 17, primary, AR (CIT)
• Microcephaly 2, primary, AR, with/-out cortical malformations (WDR62)
• Microcephaly 20, primary, AR (KIF14)
• Microcephaly 26, primary, AD (LMNB1)
• Microcephaly 3, primary, AR (CDK5RAP2)
• Microcephaly 4, primary, AR (KNL1)
• Microcephaly 5, primary, AR (ASPM)
• Microcephaly 6, primary, AR (CENPJ)
• Microcephaly 7, primary, AR (STIL)
• Microcephaly 8, primary, AR (CEP135)
• Microcephaly 9, primary, AR (CEP152)
• Microcephaly with/-out chorioretinopathy, lymphedema, or mental retardation (KIF11)
• Microcephaly, congenital cataract + psoriasiform dermatitis (MSMO1)
• Microcephaly, developmental delay + brittle hair syndrome (CARS1)
• Microcephaly, epilepsy + diabetes syndrome (IER3IP1)
• Microcephaly, epilepsy + diabetes syndrome 2 (YIPF5)
• Microcephaly, facial dysmorphism, renal agenesis + ambiguous genitalia syndrome (CTU2)
• Microcephaly, growth deficiency, seizures + brain malformations (WDR4)
• Microcephaly, growth deficiency, severe global developmental delay [panelapp] (ZNF668)
• Microcephaly, intellectual disability, epilepsy [panelapp] (AGMO)
• Microcephaly, postnatal progressive, with seizures + brain atrophy (MED17)
• Microcephaly, progressive, seizures, cerebral + cerebellar atrophy (QARS1)
• Microcephaly, seizures, developmental delay (PNKP)
• Microcephaly, short stature, impaired glucose metabolism 1 (TRMT10A)
• Microcephaly, short stature, impaired glucose metabolism 2 (PPP1R15B)
• Microcephaly, short stature, polymicrogyria with seizures (RTTN)
• Microcephaly, short stature, polymicrogyria with seizures (SASS6)
• Microcephaly-capillary malformation syndrome (STAMBP)
• Mosaic variegated aneuploidy syndrome 1 (BUB1B)
• Mosaic variegated aneuploidy syndrome 2 (CEP57)
• Mowat-Wilson syndrome (ZEB2)
• Mullegama-Klein-Martinez syndrome (STAG2)
• Multinucleated neurons, anhydramnios, renal dysplasia, cereb. hypoplasia, hydranencephaly (CEP55)
• Mungan syndrome (RAD21)
• Neurodegeneration with brain iron accumulation 6 (COASY)
• Neurodevel. disorder, microcephaly, impaired language, epilepsy, gait abnormalities, AD (NARS)
• Neurodevel. disorder, microcephaly, impaired language, gait abnormalities, AR (NARS)
• Neurodevelopmental abnormality [HP:0012759] (PCDHGC4)
• Neurodevelopmental disorder + structural brain anomalies with/-out seizures, spasticity (PTPN23)
• Neurodevelopmental disorder with ataxia, hypotonia + microcephaly (SVBP)
• Neurodevelopmental disorder with cerebral atrophy + variable facial dysmorphism (TTC5)
• Neurodevelopmental disorder with dysmorphic facies + distal limb anomalies (BPTF)
• Neurodevelopmental disorder with dysmorphic facies + distal skeletal anomalies (ZMIZ1)
• Neurodevelopmental disorder with hypotonia, microcephaly + seizures (ADARB1)
• Neurodevelopmental disorder with microcephaly + gray sclerae
• Neurodevelopmental disorder with microcephaly + spastic paraplegia (GPT2)
• Neurodevelopmental disorder with microcephaly + structural brain anomalies (DYNC1I2)
• Neurodevelopmental disorder with microcephaly, arthrogryposis + structural brain anomalies (SMPD4)
• Neurodevelopmental disorder with microcephaly, ataxia + seizures (SARS1)
• Neurodevelopmental disorder with microcephaly, cortical malformations, spasticity (TMX2)
• Neurodevelopmental disorder with microcephaly, epilepsy, brain atrophy (TRAPPC6B)
• Neurodevelopmental disorder with microcephaly, hypotonia + variable brain anomalies (PRUNE1)
• Neurodevelopmental disorder with microcephaly, seizures, cortical atrophy (VARS1)
• Neurodevelopmental disorder with progressive microcephaly, spasticity + brain anomalies (PLAA)
• Neurodevelopmental disorder with progressive microcephaly, spasticity, brain abnormalities (MFSD2A)
• Neurodevelopmental disorder with seizures + brain atrophy (EXOC7)
• Neurodevelopmental disorder with severe motor impairment + absent language (DHX30)
• Neurodevelopmental disorder with spastic diplegia + visual defects (CTNNB1)
• Neurodevelopmental disorder with spasticity + poor growth (UFC1)
• Neurodevelopmental disorder, progressive spasticity + brain white matter abnormalities (HPDL)
• Neurooculocardiogenitourinary syndrome (WDR37)
• Okur-Chung neurodevelopmental syndrome (CSNK2A1)
• Pachygyria, microcephaly, developmental delay, dysmorphic face, with/-out seizures (TUBGCP2)
• Periventricular heterotopia with microcephaly (ARFGEF2)
• Pontocerebellar hypoplasia type 1A (VRK1)
• Pontocerebellar hypoplasia type 2A (TSEN54)
• Pontocerebellar hypoplasia type 4 (TSEN54)
• Pontocerebellar hypoplasia type 5 (TSEN54)
• Pontocerebellar hypoplasia, type 12 (COASY)
• Pontocerebellar hypoplasia, type 14 (PPIL1)
• Pontocerebellar hypoplasia, type 16 (MINPP1)
• Pyruvate dehydrogenase E1-alpha deficiency (PDHA1)
• Renpenning syndrome (PQBP1)
• Rett syndrome, congenital variant (FOXG1)
• Rubinstein-Taybi syndrome 1 (CREBBP)
• Seckel syndrome 1 (ATR)
• Seckel syndrome 2 (RBBP8)
• Seckel syndrome 4 (CENPJ)
• Seckel syndrome 5 (CEP152)
• Seckel syndrome 9 (TRAIP)
• Seizures, abnormality of the corpus callosum [panelapp] (VPS50)
• Seizures, cortical blindness, microcephaly syndrome (DIAPH1)
• Short stature, microcephaly + endocrine dysfunction (XRCC4)
• Short stature, rhizomelic, with microcephaly, micrognathia + developmental delay (ARCN1)
• Smith-Lemli-Opitz syndrome (DHCR7)
• Spastic paraplegia 51, AR (AP4E1)
• Spastic tetraplegia, thin corpus callosum + progressive microcephaly (SLC1A4)
• Stromme syndrome (CENPF)
• Stuttering, familial persistent, 1 (AP4E1)
• Tatton-Brown-Rahman syndrome (DNMT3A)
• Trichothiodystrophy 6, nonphotosensitive (GTF2E2)
• Van Esch-O'Driscoll syndrome (POLA1)
• Verheij syndrome (PUF60)
• Warburg micro syndrome 1 (RAB3GAP1)
• Warsaw breakage syndrome (DDX11)
• White-Sutton syndrome (POGZ)