Delayed speech and language development, and Headache

Low match ABETAL34V AMYLOIDOSIS

Hereditary cerebral hemorrhage with amyloidosis (HCHWA), Piedmont type is a form of HCHWA (see this term) characterized by an age of onset between 50-70 years of age, recurrent lobar intracerebral hemorrhages and cognitive decline.

ABETAL34V AMYLOIDOSIS Is also known as abeta amyloidosis, piedmont type; abetal34v-related amyloidosis; hchwa, piedmont type; hereditary cerebral hemorrhage with amyloidosis, piedmont type

• Intellectual disability
• Global developmental delay
• Coma
• Behavioral abnormality
• Dementia

SOURCES: ORPHANET

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 EPISODIC ATAXIA TYPE 1

Episodic ataxia type 1 (EA1) is a frequent form of Hereditary episodic ataxia (EA; see this term) characterized by brief episodes of ataxia, neuromyotonia, and continuous interictal myokymia.

EPISODIC ATAXIA TYPE 1 Is also known as episodic ataxia with myokymia

• Scoliosis
• Motor delay
• Delayed speech and language development
• Dysarthria
• Cerebellar atrophy

SOURCES: ORPHANET

Low match MIGRAINE, FAMILIAL HEMIPLEGIC, 2; FHM2

MIGRAINE, FAMILIAL HEMIPLEGIC, 2; FHM2 Is also known as mhp2

• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay
• Pica

SOURCES: UMLS OMIM MONDO GARD

Low match GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1

GLUT1 deficiency syndrome-1 is a neurologic disorder showing wide phenotypic variability. The most severe 'classic' phenotype comprises infantile-onset epileptic encephalopathy associated with delayed development, acquired microcephaly, motor incoordination, and spasticity. Onset of seizures, usually characterized by apneic episodes, staring spells, and episodic eye movements, occurs within the first 4 months of life. Other paroxysmal findings include intermittent ataxia, confusion, lethargy, sleep disturbance, and headache. Varying degrees of cognitive impairment can occur, ranging from learning disabilities to severe mental retardation. Hypoglycorrhachia (low CSF glucose, less than 40 mg/dl) and low CSF lactate are essentially diagnostic for the disorder. As more cases with GLUT1 deficiency syndrome were described, the phenotype was broadened to include individuals with ataxia and mental retardation but without seizures, individuals with dystonia and choreoathetosis, and rare individuals with absence seizures and no movement disorder. The disorder, which results from a defect in the GLUT1 glucose transporter causing decreased glucose concentration in the central nervous system, is part of a spectrum of neurologic phenotypes resulting from GLUT1 deficiency. GLUT deficiency syndrome-2 (OMIM ) represents the less severe end of the phenotypic spectrum and is associated with paroxysmal exercise-induced dystonia with or without seizures. Correct diagnosis of GLUT1 deficiency is important because a ketogenic diet often results in marked clinical improvement of the motor and seizure symptoms (reviews by Pascual et al., 2004 and Brockmann, 2009).

GLUT1 DEFICIENCY SYNDROME 1; GLUT1DS1 Is also known as glucose transport defect, blood-brain barrier;de vivo disease; glucose transporter type 1 deficiency; glut-1 deficiency syndrome; glut1-ds

• Autosomal recessive inheritance
• Autosomal dominant inheritance
• Intellectual disability
• Seizures
• Global developmental delay

SOURCES: MESH ORPHANET OMIM GARD MONDO UMLS

Low match CHROMOSOME 16p11.2 DELETION SYNDROME, 220-KB

The deletion of a 220-kb region on chromosome 16p11.2 encompassing approximately 9 genes, including the SH2B1 gene (OMIM ), is associated with a highly penetrant form of isolated severe early-onset obesity as well as obesity with developmental delay (summary by Bachmann-Gagescu et al., 2010).An extended 1.7-Mb deletion of chromosome 16p11.2 containing both the 220-kb region and the proximal 593-kb region associated autism (see {611913}) has been reported in 2 patients with a syndrome of autism, mental retardation, and obesity and in 2 patients with pervasive developmental disorder, auditory processing difficulties, and attention deficit-hyperactivity disorder but not obesity.For a phenotypic description and a discussion of genetic heterogeneity of body mass index (BMI), see {606641}.

CHROMOSOME 16p11.2 DELETION SYNDROME, 220-KB Is also known as ;distal del(16)(p11.2); distal monosomy 16p11.2

• Intellectual disability
• Seizures
• Global developmental delay
• Delayed speech and language development
• Kyphosis

SOURCES: OMIM DOID MONDO ORPHANET UMLS

Low match PHOSPHOGLYCERATE KINASE 1 DEFICIENCY

Phosphoglycerate kinase-1 deficiency is an X-linked recessive condition with a highly variable clinical phenotype that includes hemolytic anemia, myopathy, and neurologic involvement. Patients can express 1, 2, or all 3 of these manifestations (Shirakawa et al., 2006).

PHOSPHOGLYCERATE KINASE 1 DEFICIENCY Is also known as pgk1 deficiency;gsd due to phosphoglycerate kinase 1 deficiency; glycogenosis due to phosphoglycerate kinase 1 deficiency

• Intellectual disability
• Seizures
• Global developmental delay
• Short stature
• Ataxia

SOURCES: MESH GARD MONDO OMIM ORPHANET NCIT UMLS

Low match FLOATING-HARBOR SYNDROME; FLHS

Floating-Harbor syndrome is a rare genetic disorder characterized by proportionate short stature, delayed bone age, delayed speech development, and typical facial features. The face is triangular with deep-set eyes, long eyelashes, bulbous nose, wide columella, short philtrum, and thin lips (Lacombe et al., 1995).Rubinstein-Taybi syndrome (see {180849}), which shows phenotypic overlap with Floating-Harbor syndrome, is caused by mutation in the CREBBP gene (OMIM ), for which SRCAP is a coactivator.

FLOATING-HARBOR SYNDROME; FLHS Is also known as ;

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

SOURCES: MONDO SCTID MESH ORPHANET GARD UMLS OMIM

Low match ALTERNATING HEMIPLEGIA OF CHILDHOOD 2; AHC2

Alternating hemiplegia of childhood is a rare syndrome characterized by infantile onset of episodic hemi-or quadriplegia. Most cases are accompanied by dystonic posturing, choreoathetoid movements, abnormal ocular movements, developmental delay, and progressive cognitive impairment (summary by Heinzen et al., 2012).For discussion of genetic heterogeneity of alternating hemiplegia of childhood, see AHC1 (OMIM ).

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

SOURCES: MONDO UMLS OMIM

Low match PORENCEPHALY 2; POREN2

Porencephaly is a neurologic disorder characterized by fluid-filled cysts or cavities in the brain and is thought to result from disturbed vascular supply leading to cerebral degeneration. Affected individuals typically have hemiplegia, seizures, and intellectual disability, although the severity is variable (summary by Yoneda et al., 2012).For a discussion of genetic heterogeneity of porencephaly, see POREN1 (OMIM ).

• Autosomal dominant inheritance
• Seizures
• Global developmental delay
• Strabismus
• Spasticity

SOURCES: OMIM MONDO UMLS