Delayed speech and language development, and Bipolar affective disorder

Medium match CHROMOSOME 15q13.3 DELETION SYNDROME

Heterozygous deletion of chromosome 15q13.3 is associated with a highly variable phenotype, even within families segregating the same deletion. Individuals with the deletion may have mild to moderate mental retardation or learning difficulties, or may have no cognitive deficits. Some individuals have epilepsy. Various dysmorphic features have been described, but there is no consistent or recognizable phenotype (review by van Bon et al., 2009). Patients with homozygous deletions in this region have severe neurodevelopmental problems, with epileptic encephalopathy, hypotonia, and poor growth (Endris et al., 2010).

CHROMOSOME 15q13.3 DELETION SYNDROME Is also known as chromosome 15q13.3 microdeletion syndrome;del(15)(q13.3); monosomy 15q13.3

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

SOURCES: ORPHANET GARD OMIM UMLS MONDO MESH DOID SCTID

Medium match CHROMOSOME 3q29 DELETION SYNDROME

3q29 microdeletion syndrome is a recurrent subtelomeric deletion syndrome with variable clinical manifestations including intellectual deficit and dysmorphic features.

CHROMOSOME 3q29 DELETION SYNDROME Is also known as microdeletion 3q29 syndrome;3q subtelomere deletion syndrome; 3qter deletion; del(3)(q29); monosomy 3q29; monosomy 3qter

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

SOURCES: OMIM MONDO ORPHANET UMLS SCTID MESH GARD DOID

Medium match VELOCARDIOFACIAL SYNDROME

VELOCARDIOFACIAL SYNDROME Is also known as chromosome 22q11.2 deletion syndrome, vcf syndrome;vcfs, shprintzen vcf syndrome

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

SOURCES: OMIM

Medium match DIGEORGE SYNDROME; DGS

DiGeorge syndrome (DGS) comprises hypocalcemia arising from parathyroid hypoplasia, thymic hypoplasia, and outflow tract defects of the heart. Disturbance of cervical neural crest migration into the derivatives of the pharyngeal arches and pouches can account for the phenotype. Most cases result from a deletion of chromosome 22q11.2 (the DiGeorge syndrome chromosome region, or DGCR). Several genes are lost including the putative transcription factor TUPLE1 which is expressed in the appropriate distribution. This deletion may present with a variety of phenotypes: Shprintzen, or velocardiofacial, syndrome (VCFS ); conotruncal anomaly face (or Takao syndrome); and isolated outflow tract defects of the heart including tetralogy of Fallot, truncus arteriosus, and interrupted aortic arch. A collective acronym CATCH22 has been proposed for these differing presentations. A small number of cases of DGS have defects in other chromosomes, notably 10p13 (see {601362}). In the mouse, a transgenic Hox A3 (Hox 1.5) knockout produces a phenotype similar to DGS as do the teratogens retinoic acid and alcohol.

DIGEORGE SYNDROME; DGS Is also known as chromosome 22q11.2 deletion syndrome, hypoplasia of thymus and parathyroids, third and fourth pharyngeal pouch syndrome

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

SOURCES: OMIM

Medium match HUNTINGTON DISEASE-LIKE 1; HDL1

HUNTINGTON DISEASE-LIKE 1; HDL1 Is also known as huntington-like neurodegenerative disorder 1;hln1, huntington-like neurodegenerative disorder, autosomal dominant, prion disease, early-onset, with prominent psychiatric features;early-onset prion disease with prominent psychiatric features; hdl1

• Autosomal dominant inheritance
• Seizures
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: UMLS OMIM MONDO ORPHANET DOID MESH

Medium match EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 44; EIEE44

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

SOURCES: OMIM UMLS MONDO

Medium match LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM

Vanishing white matter leukodystrophy is an autosomal recessive neurologic disorder characterized by variable neurologic features, including progressive cerebellar ataxia, spasticity, and cognitive impairment associated with white matter lesions on brain imaging. The age at onset can range from early infancy to adulthood. Rapid neurologic deterioration can occur following minor head trauma. Female mutation carriers may develop ovarian failure, manifest as primary amenorrhea or as secondary amenorrhea lasting more than 6 months, associated with elevated gonadotropin levels at age less than 40 years (summary by Van der Knaap et al., 1998 and Schiffmann et al., 1997).

LEUKOENCEPHALOPATHY WITH VANISHING WHITE MATTER; VWM Is also known as childhood ataxia with central nervous system hypomyelinization;cach, vanishing white matter leukodystrophy, cree leukoencephalopathy;cle

• Autosomal recessive inheritance
• Seizures
• Generalized hypotonia
• Pica
• Ataxia

SOURCES: ORPHANET OMIM

Medium match HUNTINGTON DISEASE; HD

Huntington disease (HD) is an autosomal dominant progressive neurodegenerative disorder with a distinct phenotype characterized by chorea, dystonia, incoordination, cognitive decline, and behavioral difficulties. There is progressive, selective neural cell loss and atrophy in the caudate and putamen. Walker (2007) provided a detailed review of Huntington disease, including clinical features, population genetics, molecular biology, and animal models.

HUNTINGTON DISEASE; HD Is also known as huntington chorea;huntington chorea

• Autosomal dominant inheritance
• Seizures
• Pica
• Ataxia
• Cognitive impairment

SOURCES: ORPHANET OMIM UMLS ICD10 SCTID

Medium match MENTAL RETARDATION, X-LINKED, SYNDROMIC 13; MRXS13

The MECP2 gene is mutated in Rett syndrome (RTT ), a severe neurodevelopmental disorder that almost always occurs in females. Males with non-RTT mutations in the MECP2 gene can demonstrate a wide variety of phenotypes, including X-linked mental retardation with spasticity and other variable features, described here, and Lubs X-linked mental retardation syndrome (MRXSL ). Males with RTT-associated MECP2 mutations have neonatal severe encephalopathy that is usually lethal (OMIM ) (Moog et al., 2003; Villard, 2007).

MENTAL RETARDATION, X-LINKED, SYNDROMIC 13; MRXS13 Is also known as mental retardation, x-linked 79;mrx79, mental retardation, x-linked 16;mrx16, mental retardation, x-linked, with spasticity, mental retardation with psychosis, pyramidal signs, and macroorchidism;ppmx;lindsay-burn syndrome; ppm-x

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

SOURCES: UMLS MONDO GARD ORPHANET OMIM SCTID DOID

Medium match SPINOCEREBELLAR ATAXIA 7; SCA7

Spinocerebellar ataxia-7 (SCA7) is an autosomal dominant neurodegenerative disorder characterized by adult onset of progressive cerebellar ataxia associated with pigmental macular dystrophy. In her classification of ataxia, Harding (1982) referred to progressive cerebellar ataxia with pigmentary macular degeneration as type II ADCA (autosomal dominant cerebellar ataxia). The age at onset, degree of severity, and rate of progression vary among and within families. Associated neurologic signs, such as ophthalmoplegia, pyramidal or extrapyramidal signs, deep sensory loss, or dementia, are also variable. Genetic anticipation is observed and is greater in paternal than in maternal transmissions (Benomar et al., 1994; summary by David et al., 1996).For a general discussion of autosomal dominant spinocerebellar ataxia, see SCA1 (OMIM ).

SPINOCEREBELLAR ATAXIA 7; SCA7 Is also known as olivopontocerebellar atrophy iii;opca3, opca iii, opca with retinal degeneration, opca with macular degeneration and external ophthalmoplegia, autosomal dominant cerebellar ataxia, type ii, adca, type ii;ataxia with pigmentary retinopathy; cerebellar syndrome-pigmentary maculopathy syndrome; sca7

• Autosomal dominant inheritance
• Global developmental delay
• Generalized hypotonia
• Ataxia
• Nystagmus

SOURCES: DOID GARD ORPHANET MONDO SCTID UMLS OMIM NCIT