Klinische FragestellungSchlafstörungen, sekundär; Differentialdiagnose

NGS +

[Sanger]

Während bei der Erkennung von genetisch bedingten Schlafstörungen bei Erwachsenen Fortschritte erzielt wurden, werden dieselben Störungen, von denen bis zu 30% gesunder Kinder betroffen sind, immer noch zu selten erkannt. Angeborene Stoffwechsel-Erkrankungen und nicht-metabolische genetische Syndrome manifestieren sich meist in der frühen Kindheit mit fortschreitenden neuromuskulären, skelettalen und/oder neurokognitiven Auffälligkeiten. Die betroffenen Kinder leiden häufig unter unzureichendem Schlaf, der mit ebenfalls beeinträchtigter Atmung einhergeht. Schlafbezogene Atmungsstörungen sind in der Allgemeinbevölkerung recht häufig. Dennoch werden Kinder und junge Erwachsene mit genetisch bedingten Leiden, die mit schlafbezogenen Atmungsstörungen einhergehen, nur selten auch molekulargenetisch untersucht. Insgesamt stellt sich die Genetik schlafbezogener Störungen als äußerst heterogen dar, und nur selten lassen sich monogene Ursachen eindeutig nachweisen.

Referenz: https://www.frontiersin.org/articles/10.3389/fneur.2014.00133/full

• Def.: secondary sleep disorders due to underlying medical conditions
• Alias: MECP2-related severe neonatal encephalopathy (MECP2)
• Allelic: Brachyolmia type 3 (TRPV4)
• Allelic: Chondrosarcoma (EXT1)
• Allelic: Digital arthropathy-brachydactyly, familial (TRPV4)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 12 (SLC2A1)
• Allelic: Epilepsy, idiopathic generalized, susceptibility to, 16 (KCNMA1)
• Allelic: Epilepsy, juvenile myoclonic, susceptibility to, 6 (CACNB4)
• Allelic: Hereditary motor + sensory neuropathy, type IIc (TRPV4)
• Allelic: Leukemia, juvenile myelomonocytic (NF1)
• Allelic: Metatropic dysplasia (TRPV4)
• Allelic: Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Allelic: Premature ovarian failure 1 (FMR1_CCG)
• Allelic: Retinitis pigmentosa 73 (HGSNAT)
• Allelic; Epilepsy, idiopathic generalized, susceptibility to, 9 (CACNB4)
• AD nocturnal frontal lobe epilepsy (CRH)
• ATP1A3-related neurologic disorders (ATP1A3)
• Achondroplasia (FGFR3)
• Acromicric dysplasia (FBN1)
• Advanced sleep-phase syndrome, familial, 2 (CSNK1D)
• Alexander disease (GFAP)
• Alternating hemiplegia of childhood 1 (ATP1A2)
• Alternating hemiplegia of childhood 2 (ATP1A3)
• Angelman syndrome (UBE3A)
• Antley-Bixler syndrome without genital anomalies or disordered steroidogenesis (FGFR2)
• Anxiety-related personality traits (SLC6A4)
• Apert syndrome (FGFR2)
• Aphasia, primary progressive (GRN)
• Aspartylglucosaminuria (AGA)
• Avascular necrosis of femoral head, primary, 2 (TRPV4)
• Bainbridge-Ropers syndrome (ASXL3)
• Beare-Stevenson cutis gyrata syndrome (FGFR2)
• Becker muscular dystrophy (DMD)
• Bent bone dysplasia syndrome (FGFR2)
• Bohring-Opitz syndrome (ASXL1)
• Brachyolmia type 3 (TRPV4)
• CAPOS syndrome (ATP1A3)
• CATSHL syndrome (FGFR3)
• CHARGE syndrome (CHD7, SEMA3E)
• Cardiomyopathy, dilated, 3B (DMD)
• Carpenter syndrome (RAB23)
• Central hypoventilation syndrome, congenital, 1, +/- Hirschsprung disease (PHOX2B)
• Cerebellar ataxia, deafness, and narcolepsy, AD (DNMT1)
• Cerebellar atrophy, developmental delay, seizures (KCNMA1)
• Ceroid lipofuscinosis, neuronal, 1 (PPT1)
• Ceroid lipofuscinosis, neuronal, 10 (CTSD)
• Ceroid lipofuscinosis, neuronal, 11 (GRN)
• Ceroid lipofuscinosis, neuronal, 13 (Kufs type), AD (CTSF)
• Ceroid lipofuscinosis, neuronal, 2 (TPP1)
• Ceroid lipofuscinosis, neuronal, 3 (CLN3)
• Ceroid lipofuscinosis, neuronal, 4A (Kufs type), AR (CLN6)
• Ceroid lipofuscinosis, neuronal, 4B (Kufs type), AD (DNAJC5)
• Ceroid lipofuscinosis, neuronal, 5 (CLN5)
• Ceroid lipofuscinosis, neuronal, 6 (CLN6)
• Ceroid lipofuscinosis, neuronal, 7 (MFSD8)
• Ceroid lipofuscinosis, neuronal, 8 (CLN8)
• Ceroid lipofuscinosis, neuronal, 8, Northern epilepsy variant (CLN8)
• Charcot-Marie-Tooth disease, dominant intermediate D (MPZ)
• Charcot-Marie-Tooth disease, type 1A + 1E (PMP22)
• Charcot-Marie-Tooth disease, type 1B, 2I, 2J (MPZ)
• Charcot-Marie-Tooth neuropathy, XLD, 1 (GJB1)
• Cognitive impairment with/-out cerebellar ataxia (SCN8A)
• Congenital central hypoventilation syndrome (PHOX2B)
• Convulsions, familial infantile, with paroxysmal choreoathetosis (PRRT2)
• 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)
• Craniofacial-skeletal-dermatologic dysplasia (FGFR2)
• Craniosynostosis 1 (TWIST1)
• Craniosynostosis, nonspecific (FGFR2)
• Crouzon syndrome (FGFR2)
• Crouzon syndrome with acanthosis nigricans (FGFR3)
• Dejerine-Sottas disease (MPZ, PMP22)
• Developmental + epileptic encephalopathy 14 (KCNT1)
• Developmental + epileptic encephalopathy 85 +/- midline brain defects (SMC1A)
• Developmental and epileptic encephalopathy 13 (SCN8A)
• Developmental and epileptic encephalopathy 42 (CACNA1A)
• Developmental and epileptic encephalopathy 59 (GABBR2)
• Developmental and epileptic encephalopathy 6B, non-Dravet (SCN1A)
• Developmental and epileptic encephalopathy 7 (KCNQ2)
• Developmental and epileptic encephalopathy 98 (ATP1A2)
• Digital arthropathy-brachydactyly, familial (TRPV4)
• Dravet syndrome (SCN1A)
• Duchenne muscular dystrophy (DMD)
• Dyskinesia, familial, with facial myokymia (ADCY5)
• Dyskinesia, limb + orofacial, infantile-onset (PDE10A)
• Dystonia 9 (SLC2A1)
• Dystonia, dopa-responsive, due to sepiapterin reductase deficiency (SPR)
• Dystonia-12 (ATP1A3)
• Ectopia lentis, familial (FBN1)
• Encephalopathy, neonatal severe (MECP2)
• Epilepsy, familial focal, with variable foci 1 (DEPDC5)
• Epilepsy, nocturnal frontal lobe, 1 (CHRNA4)
• Epilepsy, nocturnal frontal lobe, 3 (CHRNB2)
• Epilepsy, nocturnal frontal lobe, 5 (KCNT1)
• Epilepsy, nocturnal frontal lobe, type 4 (CHRNA2)
• Epilepsy, progressive myoclonic 3, with/-out intracellular inclusions (KCTD7)
• Episodic ataxia, type 2 (CACNA1A)
• Episodic ataxia, type 5 (CACNB4)
• Episodic ataxia, type 6 (SLC1A3)
• Episodic ataxia/myokymia syndrome (KCNA1)
• Episodic kinesigenic dyskinesia 1 (PRRT2)
• Exostoses, multiple, type 1 [1 family] (EXT1)
• Exudative vitreoretinopathy 2, XL (NDP)
• Febrile seizures, familial, 3A (SCN1A)
• Fetal akinesia, respiratory insufficiency, microcephaly, polymicrogyria, dysmorphic face (ATP1A2)
• Fragile X syndrome (FMR1_CCG)
• Fragile X tremor/ataxia syndrome (FMR1_CCG)
• Friedreich ataxia (FXN_GAA, FXN)
• Friedreich ataxia with retained reflexes (FXN)
• Frontotemporal lobar degeneration with ubiquitin-positive inclusions (GRN)
• GLUT1 deficiency syndrome 1, infantile onset, severe (SLC2A1)
• GLUT1 deficiency syndrome 2, childhood onset (SLC2A1)
• Geleophysic dysplasia 2 (FBN1)
• Generalized epilepsy with febrile seizures plus, type 2 (SCN1A)
• Glycogen storage disease II (GAA)
• Hartsfield syndrome (FGFR1)
• Hereditary motor + sensory neuropathy, type IIc (TRPV4)
• Hirschsprung disease, susceptibility to, 3 (GDNF)
• Hyperekplexia 1 (GLRA1)
• Hyperekplexia 2 (GLRB)
• Hyperekplexia 3 (SLC6A5)
• Hyperekplexia 4 (ATAD1)
• Hypochondroplasia (FGFR3)
• Hypogonadotropic hypogonadism 2 +/- anosmia (FGFR1)
• Hypogonadotropic hypogonadism 5 with/-out anosmia (CHD7)
• Hypomyelinating neuropathy, congenital, 2 (MPZ)
• Intellectual developmental disorder + paroxysmal dyskinesia/seizures (PDE2A)
• Jackson-Weiss syndrome (FGFR1)
• Jackson-Weiss syndrome (FGFR2)
• Kleefstra syndrome 1 (EHMT1)
• Koolen-De Vries syndrome (KANSL1)
• LADD syndrome (FGFR2, FGFR3)
• Leukodystrophy, hypomyelinating, 11 (POLR1C)
• Liang-Wang syndrome (KCNMA1)
• Lymphangioleiomyomatosis (TSC1)
• MASS syndrome (FBN1)
• Macular dystrophy with central cone involvement (MFSD8)
• Marfan lipodystrophy syndrome (FBN1)
• Marfan syndrome (FBN1)
• Medullary thyroid carcinoma (RET)
• Mental retardation, AD 1 (MBD5)
• Mental retardation, AD 46 (KCNQ5)
• Mental retardation, AD 52 (ASH1L)
• Mental retardation, AR 65 (KDM5B)
• Mental retardation, AR, 37 (ANK3)
• Mental retardation, XL syndromic, Lubs type (MECP2)
• Mental retardation, XL, syndromic 13 (MECP2)
• Metatropic dysplasia (TRPV4)
• Migraine, familial basilar (ATP1A2)
• Migraine, familial hemiplegic, 1 (CACNA1A)
• Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia (CACNA1A)
• Migraine, familial hemiplegic, 2 (ATP1A2)
• Migraine, familial hemiplegic, 3 (SCN1A)
• Migraine, with/-out aura, susceptibility to, 13 (KCNK18)
• Mucopolysaccharidosis II (IDS)
• Mucopolysaccharidosis IVA (GALNS)
• Mucopolysaccharidosis Ih, Ih/s, Is (IDUA)
• Mucopolysaccharidosis type IIIA [Sanfilippo A] (SGSH)
• Mucopolysaccharidosis type IIIB [Sanfilippo B] (NAGLU)
• Mucopolysaccharidosis type IIIC [Sanfilippo C] (HGSNAT)
• Mucopolysaccharidosis type IIID (GNS)
• Muenke syndrome (FGFR3)
• Multiple congenital anomalies-hypotonia-seizures syndrome 2 (PIGA)
• Multiple endocrine neoplasia IIA + IIB (RET)
• Multiple sufatase deficiency (SUMF1)
• Mungan syndrome (RAD21)
• Myoclonus, familial, 2 (SCN8A)
• Myokymia (KCNQ2)
• Myotonic dystrophy 1 (DMPK)
• Myotonic dystrophy 2 (CNBP)
• Narcolepsy 7 (MOG)
• Neuroblastoma with Hirschsprung disease (PHOX2B)
• Neurodevelopmental disorder with hypotonia, autism +/- hyperkinesis (VAMP2)
• Neurodevelopmental disorder with hypotonia, impaired expressive language +/- seizures (DEAF1)
• Neurodevelopmental disorder with hypotonia, variable intellectual, behavioral abnormalities (POLR2A)
• Neurodevelopmental disorder with poor language + loss of hand skills (GABBR2)
• Neurofibromatosis, familial spinal (NF1)
• Neurofibromatosis, type 1 (NF1)
• Neurofibromatosis, type 2 (NF2)
• Neurofibromatosis-Noonan syndrome (NF1)
• Neuronopathy, distal hereditary motor, type VIII (TRPV4)
• Neuropathy, hereditary sensory, type IE (DNMT1)
• Neuropathy, inflammatory demyelinating (PMP22)
• Neuropathy, recurrent, with pressure palsies (PMP22)
• Niemann-Pick disease, type C1 + D (NPC1)
• Niemann-Pick disease, type C2 (NPC2)
• Norrie disease (NDP)
• Obsessive-compulsive disorder (SLC6A4)
• Osteoglophonic dysplasia (FGFR1)
• Parastremmatic dwarfism (TRPV4)
• Paroxysmal nonkinesigenic dyskinesia 1 (PNKD)
• Paroxysmal nonkinesigenic dyskinesia, 3, with/-out generalized epilepsy (KCNMA1)
• Pfeiffer syndrome (FGFR1, FGFR2)
• Pfeiffer syndrome (FGFR2)
• Phelan-McDermid syndrome SHANK3)
• Pheochromocytoma (RET)
• Pitt-Hopkins syndrome (TCF4)
• Pontocerebellar hypoplasia type 2D (SEPSECS)
• Prader-Willi syndrome (NDN, SNRPN)
• Pycnodysostosis (CTSK)
• Pycnodysostosis, Toulouse-Lautrec Syndrome (CTSK)
• Rett syndrome (MECP2)
• Rett syndrome, atypical (MECP2)
• Rett syndrome, preserved speech variant (MECP2)
• Ritscher-Schinzel syndrome (CCDC22)
• Ritscher-Schinzel syndrome (WASHC5)
• Robinow-Sorauf syndrome (TWIST1)
• Roussy-Levy syndrome (MPZ, PMP22)
• SADDAN (FGFR3)
• SED, Maroteaux type (TRPV4)
• Saethre-Chotzen syndrome (FGFR2)
• Saethre-Chotzen syndrome (TWIST1)
• Saethre-Chotzen syndrome +/- eyelid anomalies (TWIST1)
• Scaphocephaly + Axenfeld-Rieger anomaly (FGFR2)
• Scaphocephaly, maxillary retrusion + mental retardation (FGFR2)
• Scapuloperoneal spinal muscular atrophy (TRPV4)
• Schaaf-Yang syndrome (MAGEL2)
• Schizophrenia 15 (SHANK3)
• Segawa syndrome, AR (TH)
• Seizures, benign familial infantile, 2 (PRRT2)
• Seizures, benign familial infantile, 5 (SCN8A)
• Seizures, benign neonatal, 1 (KCNQ2)
• Simpson-Golabi-Behmel syndrome, type 1 (GPC3, GPC4)
• Simpson-Golabi-Behmel syndrome, type 2 (OFD1)
• Smith-Lemli-Opitz syndrome (DHCR7)
• Smith-Magenis syndrome (RAI1)
• Spastic paraplegia 8, AD (WASHC5)
• Spinal muscular atrophy 1-4 (SMN1)
• Spinocerebellar ataxia 6 (CACNA1A)
• Spinocerebellar ataxia, AR 7 (TPP1)
• Spondylometaphyseal dysplasia, Kozlowski type (TRPV4)
• Squalene synthase deficiency (FDFT1)
• Stiff skin syndrome (FBN1)
• Stomatin-deficient cryohydrocytosis with neurologic defects (SLC2A1)
• Striatal degeneration, AD (PDE10A)
• Sweeney-Cox syndrom (TWIST1)
• Syndromic/ nonsyndromic intellectual disability (MECP2)
• TARP [talipes equinovarus, atrial septal def., Robin s., pers. left sup. vena cava] syndrome (RBM19)
• Thanatophoric dysplasia, type I + II (FGFR3)
• Treacher Collins syndrome 1 (TCOF1)
• Treacher Collins syndrome 2 (POLR1D)
• Treacher Collins syndrome 3 (POLR1C)
• Trigonocephaly 1 (FGFR1)
• Tuberous sclerosis-1 (TSC1)
• Tuberous sclerosis-2 (TSC2)
• Vulto-van Silfout-de Vries syndrome (DEAF1)
• Waardenburg syndrome, type 4B (EDN3)
• Watson syndrome (NF1)
• Weill-Marchesani syndrome 2, AD (FBN1)
• Wilson disease (ATP7B)
• ataxia syndrome (FMR1_CCG)