Abnormal facial shape, and Generalized seizures

Low match MENTAL RETARDATION, AUTOSOMAL RECESSIVE 6; MRT6

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Abnormal facial shape

SOURCES: UMLS OMIM MONDO MESH

Low match MENTAL RETARDATION, X-LINKED 100; MRX100

• Intellectual disability
• Seizures
• Abnormal facial shape
• X-linked recessive inheritance
• Poor speech

SOURCES: OMIM UMLS MONDO

Low match MENTAL RETARDATION, X-LINKED 49; MRX49

Nonsyndromic mental retardation. Hypotonia in infancy, poor or absent speech, and other disorders are occasionally associated.

MENTAL RETARDATION, X-LINKED 49; MRX49 Is also known as mental retardation, x-linked 15;mrx15

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: UMLS MONDO OMIM

Low match LISSENCEPHALY 1; LIS1

Lissencephaly (LIS), literally meaning smooth brain, is characterized by smooth or nearly smooth cerebral surface and a paucity of gyral and sulcal development, encompassing a spectrum of brain surface malformations ranging from complete agyria to subcortical band heterotopia (SBH). Classic lissencephaly is associated with an abnormally thick cortex, reduced or abnormal lamination, and diffuse neuronal heterotopia. SBH consists of circumferential bands of heterotopic neurons located just beneath the cortex and separated from it by a thin band of white matter. SBH represents the less severe end of the lissencephaly spectrum of malformations (Pilz et al., 1999, summary by Kato and Dobyns, 2003). Agyria, i.e., brain without convolutions or gyri, was considered a rare malformation until recent progress in neuroradiology (Bordarier et al., 1986). With this technical advantage, a number of lissencephaly syndromes have been distinguished.Classic lissencephaly (formerly type I) is a brain malformation caused by abnormal neuronal migration at 9 to 13 weeks' gestation, resulting in a spectrum of agyria, mixed agyria/pachygyria, and pachygyria. It is characterized by an abnormally thick and poorly organized cortex with 4 primitive layers, diffuse neuronal heterotopia, enlarged and dysmorphic ventricles, and often hypoplasia of the corpus callosum. (Lo Nigro et al., 1997).Kato and Dobyns (2003) presented a classification system for neuronal migration disorders based on brain imaging findings and molecular analysis. The authors also reviewed the contributions and interactions of the 5 genes then known to cause human lissencephaly: LIS1 or PAFAH1B1, 14-3-3-epsilon (YWHAE), DCX, RELN, and ARX. Genetic Heterogeneity of LissencephalyLissencephaly is a genetically heterogeneous disorder. See also LIS2 (OMIM ), caused by mutation in the RELN gene (OMIM ) on chromosome 7q22; LIS3 (OMIM ), caused by mutation in the TUBA1A gene (OMIM ) on chromosome 12q13; LIS4 (OMIM ), caused by mutation in the NDE1 gene (OMIM ) on chromosome 16p13; LIS5 (OMIM ), caused by mutation in the LAMB1 gene (OMIM ) on chromosome 7q; LIS6 (OMIM ), caused by mutation in the KATNB1 gene (OMIM ) on chromosome 16q21; LIS7 (OMIM ), caused by mutation in the CDK5 gene (OMIM ) on chromosome 7q36; and LIS8 (OMIM ), caused by mutation in the TMTC3 gene (OMIM ) on chromosome 12q21.X-linked forms include LISX1 (OMIM ), caused by mutation in the DCX gene (OMIM ) on chromosome Xq22.3-q23, and LISX2 (OMIM ), caused by mutation in the ARX gene (OMIM ) on chromosome Xp22.3-p21.1.See also Miller-Dieker lissencephaly syndrome (MDLS ), a contiguous gene microdeletion syndrome involving chromosome 17p13 and including the PAFAH1B1 and YWHAE (OMIM ) genes. Lissencephaly caused by mutations in the PAFAH1B1 gene is also called 'isolated' lissencephaly to distinguish it from the accompanying features of MDLS.

LISSENCEPHALY 1; LIS1 Is also known as lissencephaly sequence, isolated;ils, lissencephaly, classic

• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia
• Microcephaly

SOURCES: ORPHANET OMIM

Low match INTELLECTUAL DEVELOPMENTAL DISORDER WITH NEUROPSYCHIATRIC FEATURES; IDDNPF

Intellectual developmental disorder with neuropsychiatric features is an autosomal recessive disorder characterized by moderate intellectual disability, relatively mild seizures, and neuropsychiatric abnormalities, such as anxiety, obsessive-compulsive behavior, and autistic features. Mild facial dysmorphic features may also be present (summary by Srour et al., 2017).

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: OMIM UMLS MONDO

Low match EPILEPSY, FOCAL, WITH SPEECH DISORDER AND WITH OR WITHOUT MENTAL RETARDATION; FESD

Focal epilepsy with speech disorder is a childhood-onset seizure disorder with a highly variable phenotype. Seizures typically occur in the temporal lobe, or rolandic brain region, which affects speech and language, and electroencephalogram (EEG) characteristically shows centrotemporal spike-wave discharges. EEG abnormalities often occur during sleep and may manifest as continuous spike-wave discharges during slow-wave sleep (CSWS or CSWSS). FESD represents an electroclinical spectrum that ranges from severe early-onset seizures associated with delayed psychomotor development, persistent speech difficulties, and mental retardation to a more benign entity characterized by childhood onset of mild or asymptomatic seizures associated with transient speech difficulties followed by remission of seizures in adolescence and normal psychomotor development. There is incomplete penetrance and intrafamilial variability, even among family members who carry the same GRIN2A mutation (summary by Lesca et al., 2013; Lemke et al., 2013; Carvill et al., 2013).The disorder represented here encompasses several clinical entities, including Landau-Kleffner syndrome (LKS), epileptic encephalopathy with continuous spike and wave during slow-wave sleep (ECSWS; CSWSS), autosomal dominant rolandic epilepsy, mental retardation, and speech dyspraxia (ADRESD; RESDAD), and benign epilepsy with centrotemporal spikes (BECTS; see {117100}). LKS is classically described as a childhood-onset variant of epileptic aphasia. It is associated with EEG abnormalities occurring in the temporal lobe of the language-dominant hemisphere, even in the absence of overt clinical seizures. LKS is sometimes referred to as an 'acquired aphasia' because most affected children show normal psychomotor development until the onset of seizures, usually between 3 and 7 years, although some may have prior delayed development. A hallmark of the disorder is severe impairment in auditory language comprehension and speech. Some patients may also have persistent intellectual disability or behavioral abnormalities reminiscent of autism or attention deficit-hyperactivity disorder. EEG abnormalities typically include centrotemporal spikes suggestive of rolandic epilepsy or continuous spike and waves during slow-wave sleep. The presence of CSWS is associated with more widespread behavioral and cognitive regression than LKS, although the 2 disorders may be considered part of a spectrum. There is controversy about the precise definition of LKS and its relationship to CSWS that stems mainly from the phenotypic heterogeneity of the disorder (summary by Stefanatos, 2011).

EPILEPSY, FOCAL, WITH SPEECH DISORDER AND WITH OR WITHOUT MENTAL RETARDATION; FESD Is also known as aphasia, acquired, with epilepsy

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: OMIM

Low match PITT-HOPKINS-LIKE SYNDROME 2; PTHSL2

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Generalized hypotonia
• Pica

SOURCES: MONDO UMLS OMIM

Low match HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4; HPMRS4

Hyperphosphatasia with mental retardation syndrome-4 is an autosomal recessive neurologic disorder characterized by severely delayed psychomotor development, mental retardation, lack of speech acquisition, seizures, and dysmorphic facial features. Laboratory studies show increased serum alkaline phosphatase (summary by Howard et al., 2014). The disorder is caused by a defect in glycosylphosphatidylinositol (GPI) biosynthesis.For a discussion of genetic heterogeneity of HPMRS, see HPMRS1 (OMIM ).For a discussion of genetic heterogeneity of GPI biosynthesis defects, see GPIBD1 (OMIM ).

HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4; HPMRS4 Is also known as glycosylphosphatidylinositol biosynthesis defect 10;gpibd10

• Autosomal recessive inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Generalized hypotonia

SOURCES: UMLS MONDO OMIM

Low match INTELLECTUAL DISABILITY-OBESITY-BRAIN MALFORMATIONS-FACIAL DYSMORPHISM SYNDROME

Intellectual disability-obesity-brain malformations-facial dysmorphism syndrome is a rare, syndromic intellectual disability primarily characterized by moderate to severe intellectual disability, true-to-relative microcephaly and brain abnormalities including a thin corpus callosum, cerebellar hypoplasia, cerebral white matter hypoplasia and multi-focal hyperintensity of cerebral white matter on MRI. Obesity and distinctive craniofacial dysmorphism (including brachycephaly, round face, straight eyebrows, synophrys, hypertelorism, epicanthus, wide and depressed nasal bridge, protruding ears with uplifted lobe, downslanting corners of the mouth) are additional features.

INTELLECTUAL DISABILITY-OBESITY-BRAIN MALFORMATIONS-FACIAL DYSMORPHISM SYNDROME Is also known as autosomal recessive intellectual disability due to trappc9 deficiency

• Seizures
• Global developmental delay
• Microcephaly
• Hypertelorism
• Muscular hypotonia

SOURCES: ORPHANET

Low match MENTAL RETARDATION, AUTOSOMAL DOMINANT 13; MRD13

MRD13 is an autosomal dominant form of mental retardation associated with variable neuronal migration defects resulting in cortical malformations. More variable features include early-onset seizures and mild 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).

MENTAL RETARDATION, AUTOSOMAL DOMINANT 13; MRD13 Is also known as mental retardation, autosomal dominant 13, with neuronal migration defects

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Short stature

SOURCES: MONDO UMLS DOID OMIM