IllnessSleep disorders, secondary; differential diagnosis

NGS +

[Sanger]

While some progress has been made in the detection of genetic sleep disorders in adults, the same disorders, affecting up to 30% of healthy children, are still too rarely recognized. Inborn errors of metabolism and non-metabolic genetic syndromes usually manifest in early childhood with progressive neuromuscular, skeletal and/or neurocognitive abnormalities. Affected children often suffer from inadequate sleep, which is associated with impaired breathing as well. Sleep-related breathing disorders are quite common in the general population. Nevertheless, children and young adults with genetic conditions associated with sleep-related breathing disorders are rarely also investigated by molecular genetic methods. Overall, the genetics of sleep-related disorders presents as extremely heterogeneous, and only rarely can monogenic causes be clearly demonstrated.

Reference: 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)