TaoMedAI/RareMedData huggingface dataset:
17q23.1q23.2 microdeletion syndrome (ORPHA:261279)
17q23.1q23.2 microdeletion syndrome is a recently described syndrome characterized by developmental delay, microcephaly, short stature, heart defects and limb abnormalities.
Epidemiology
It has been clinically and molecularly characterized in 7 patients.
Clinical description
All individuals had mild to moderate developmental delay, in particular speech delay. All except one had heart defects, including mainly patent ductus arteriosus or atrial septal defect. Limb abnormalities include long, thin fingers and toes, and hypoplasia of patellae. Scoliosis is also present. Patients had some mild and unspecific dysmorphic facial features.
Etiology
The syndrome is caused by an interstitial deletion encompassing 17q23.1q23.2. The deletions were characterized by comparative genomic hybridization (CGH) microarray and fluorescence in situ hybridization (FISH). The underlying mechanism is non-allelic homologous recombination (NAHR). Parental FISH testing in five of the seven cases confirmed a de novo origin. The minimal deletion region of 2.2 Mb encompasses 2 transcription factors, TBX2 and TBX4, which are good candidate genes for explaining the phenotype.

                            Last update: 
                            May 2011


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
17q24.2 microdeletion syndrome (ORPHA:529962)
A rare, genetic, multiple congenital anomalies/dysmorphic features-intellectual disability syndrome characterized by developmental and speech delay, intellectual disability, feeding difficulties, failure to thrive, growth retardation, and associated malformations such as abnormality of fingers and toes (i.e. clinodactyly of the 5th finger, 2-3 toe syndactyly), microcephaly, heart defects, and upper airways anomalies. Observed facial dysmorphism includes hypertelorism, small, narrow or downslanting palpebral fissures, ptosis, epicanthus, ear malformations, broad nasal bridge, bulbous/prominent nose, short philtrum, thin lips, retrognathia/micrognathia, arched/cleft palate, and dental anomalies. Additional variable manifestations include hearing and visual impairment, seizures, joint anomalies, obesity, and behavioral/psychiatric disorders.
19p13.12 microdeletion syndrome (ORPHA:254346)
19p13.12 microdeletion syndrome is a newly described syndrome characterized by moderate to severe developmental delay, language delay, bilateral sensorineural and/or conductive hearing loss and facial dysmorphism.
Epidemiology
It has been reported in 6 patients to date.
Clinical description
Facial dysmorphism includes brachycephaly, anteverted nares, and ear malformations. Cardiac defects and abnormal behavior characterized by auto- and hetero-aggressivity and hyperactivity can be observed.
Etiology
This interstitial microdeletion was identified by comparative genomic hybridization (CGH) microarray and its size is variable.

                            Last update: 
                            April 2011


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
19p13.13 microdeletion syndrome (ORPHA:357001)
A rare partial autosomal monosomy characterized by global developmental delay, moderate intellectual disability, macrocephaly, overgrowth, hypotonia, and facial dysmorphism (frontal bossing, down-slanting palpebral fissures). Other associated features variably include ataxia, seizures, ventriculomegaly, ocular abnormalities (strabismus, optic nerve hypoplasia) and gastrointestinal problems (abdominal pain, vomiting, constipation).
19p13.3 microduplication syndrome (ORPHA:447980)
A rare, genetic, syndromic intellectual disability characterized by intrauterine growth retardation, microcephaly, hypotonia, motor and neurodevelopmental delay, speech delay, intellectual disability, and mild dysmorphic features.
19q13.11 microdeletion syndrome (ORPHA:217346)
The 19q13.11 microdeletion is characterized by several major features including pre and postnatal growth retardation, slender habitus, severe postnatal feeding difficulties, microcephaly, intellectual deficit with speech disturbance, hypospadias and ectodermal dysplasia presented by scalp aplasia, thin and sparse hair, eyebrows and eyelashes, thin and dry skin and dysplasic nails.
Epidemiology
To date, the syndrome has been identified in five patients.
Clinical description
Minor dysmorphic features include a long face, high forehead, retrognathia, thin lips, V shaped nasal tip, hypoplastic alae nasi, prominent columella, and large and simple ears.
Etiology
The microdeletion was identified by microarray-based comparative genomic hybridization (aCGH). Haploinsufficiency of one or more genes in the 19q13.11 region could cause this microdeletion syndrome. The careful clinical examination and the molecular characterization of additional patients with a similar chromosomal anomaly are needed to further delineate the clinical features and refine the minimal critical region.

                            Last update: 
                            February 2010


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
1p21.3 microdeletion syndrome (ORPHA:293948)
1p21.3 microdeletion syndrome is an extremely rare chromosomal anomaly characterized by severe speech and language delay, intellectual deficiency, autism spectrum disorder(see this term).
Epidemiology
Less than 10 cases have been reported to date.
Clinical description
1p21.3 microdeletion syndrome is characterized by severe speech and language delay, a borderline-mild to mild-moderate intellectual deficiency, autism spectrum disorder (see this term) features, and minor dysmorphic facial features such as long ears, deep set eyes, a broad nasal tip and a thick lower lip. Affected individuals have normal gross motor development without major abnormalities, they are often very shy and friendly with a tendency to overeat.
Etiology
1p21.3 microdeletion syndrome is caused by a hemizygous interstitial microdeletion on the short arm of chromosome 1, occurring mostly de novo, that implicates DPYD (dihydropyrimidine dehydrogenase) and MIR137 genes associated with miRNA pathways.

                            Last update: 
                            November 2012


                            - Expert reviewer(s): 
                            Pr T. [Tjitske] KLEEFSTRA
1p31p32 microdeletion syndrome (ORPHA:401986)
1p31p32 microdeletion syndrome is a rare chromosomal anomaly syndrome, resulting from the partial deletion of the short arm of chromosome 1, characterized by developmental delay, corpus callosum agenesis/hypoplasia and craniofacial dysmorphism, such as macrocephaly (caused by hydrocephalus or ventriculomegaly), low-set ears, anteverted nostrils and micrognathia. Urinary tract defects (e.g. vesicoureteral reflux, urinary incontinence) are also frequently associated. Other reported variable manifestations include hypotonia, tethered spinal cord, Chiari type I malformation and seizures.
1p35.2 microdeletion syndrome (ORPHA:456298)
A rare chromosomal anomaly characterized by an intrauterine and postnatal growth retardation, short stature, developmental delay, learning difficulties, hearing loss, hypermetropia,and a recognisable facial dysmorphism including prominent forehead, long, myopathic facies, fine eyebrows, small mouth and micrognathia.
1q21.1 microdeletion syndrome (ORPHA:250989)
1q21.1 microdeletion syndrome is a newly described recurrent deletion syndrome with variable clinical manifestations but without the clinical picture of thrombocytopenia - absent radius (TAR) syndrome.
Epidemiology
It has been described in 46 patients to date.
Clinical description
The clinical phenotype is extremely variable; the most common but non-constant clinical findings include microcephaly, developmental delay or mild intellectual deficit, slight facial dysmorphic features and eye abnormalities. Congenital malformations are not common. Autism spectrum disorders, schizophrenia or attention deficit hyperactivity disorder have been noted occasionally.
Etiology
This syndrome is caused by a recurrent 1.35Mb deletion in the distal 1q21.1 region distinct from the deletion region implicated in TAR syndrome (see this term).
Diagnostic methods
This microdeletion was identified by comparative genomic hybridization (CGH) microarray and is only diagnosed by molecular cytogenetics. It cannot be identified by routine chromosome analysis.
Genetic counseling
The underlying mechanism is non-allelic homologous recombination (NAHR). Deletions appear de novo or can be inherited in an autosomal dominant manner from mildly affected or completely normal parents. This suggests that the distal 1q21.1 microdeletion has incomplete penetrance and variable expressivity.

                            Last update: 
                            March 2011


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
1q21.1 microduplication syndrome (ORPHA:250994)
1q21.1 microduplication syndrome is a rare partial autosomal trisomy/tetrasomy with incomplete penetrance and variable expression characterized by macrocephaly, developmental delay, intellectual disability, psychiatric disturbances (autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, mood disorders) and mild facial dysmorphism (high forehead, hypertelorism). Other associated features include congenital heart defects, hypotonia, short stature, scoliosis.
1q41q42 microdeletion syndrome (ORPHA:250999)
1q41q42 microdeletion syndrome is a chromosomal anomaly characterized by a severe developmental delay and/or intellectual disability, typical facial dysmorphic features, brain anomalies, seizures, cleft palate, clubfeet, nail hypoplasia and congenital heart disease.
1q44 microdeletion syndrome (ORPHA:238769)
1q44 microdeletion syndrome is a newly described syndrome associated with facial dysmorphism, developmental delay, in particular of expressive speech, seizures and hypotonia.
Epidemiology
It has been reported in four unrelated patients.
Clinical description
The most common facial features include microcephaly, hypertelorism and thin upper lip. An abnormal corpus callosum (agenesis, hypogenesis or slightly reduced thickness) is observed in all affected patients.
Etiology
This microdeletion was identified by array CGH (comparative genomic hybridization).

                            Last update: 
                            October 2010


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
2-aminoadipic 2-oxoadipic aciduria (ORPHA:79154)
A rare disorder of lysine and tryptophan metabolism characterized by 2-aminoadipic and 2-oxoadipic aciduria. Patients may also present with increased urinary excretion of alpha-hydroxyadipic acid. Variable clinical presentations have been found in patients including hypotonia, developmental delay, mild to severe intellectual disability, ataxia, epilepsy, and behavioral disorders (most commonly attention deficit hyperactivity disorder). However, many individuals with the biochemical phenotype are completely asymptomatic and thus the clinical significance of the condition is questionable.
2-hydroxyglutaric aciduria (ORPHA:19)
2-Hydroxyglutaric aciduria is a group of neurometabolic disorders with a wide clinical spectrum ranging from severe neonatal presentations to progressive forms, and asymptomatic cases, characterized biochemically by increased levels of 2-hydroxyglutaric acid in the plasma, cerebrospinal fluid and urine.
Epidemiology
The exact prevalence and incidence of the disorders are not known, but fewer than 300 patients have been reported to date.
Clinical description
There are two enantiomeric forms of 2-hydroxyglutaric acid, i.e. D-2-hydroxyglutaric acid and L-2-hydroxyglutaric acid. L-2-hydroxyglutaric aciduria (see this term) is characterized by psychomotor retardation, cerebellar ataxia and epilepsy, and D-2-hydroxyglutaric aciduria (see this term) is characterized by variable metabolic, neurological and dysmorphic manifestations.
Etiology
Mutations in the L2HGDH gene (14q22.1) gene have been implicated in L-2-hydroxyglutaric aciduria, and mutations in the D2HGDH (2q37.3) and IDH2 (15q26.1) genes in D-2-hydroxyglutaric aciduria.
Genetic counseling
L-2-hydroxyglutaric aciduria and D-2-hydroxyglutaric aciduria caused by mutations in the L2HGDH and D2HGDH genes, respectively, follow an autosomal recessive pattern of inheritance. In contrast, D-2-hydroxyglutaric aciduria caused by a specific heterozygous gain-of-function mutation in the IDH2 gene, is an autosomal dominant trait and is usually caused by de novo mutations.

                            Last update: 
                            June 2012


                            - Expert reviewer(s): 
                            Dr E.A. [Eduard] STRUYS
2-methylbutyryl-CoA dehydrogenase deficiency (ORPHA:79157)
A rare organic aciduria characterized by impaired isoleucine degradation with increased plasma or whole blood C5 acylcarnitine levels (typically observed in newborn screening) and increased urinary excretion of N-methylbutyrylglycine. The condition is usually clinically asymptomatic, although patients with muscular hypotonia, developmental delay, and seizures (among others) have been reported.
20p12.3 microdeletion syndrome (ORPHA:261295)
20p12.3 microdeletion syndrome is a recently described syndrome characterized by Wolff-Parkinson-White syndrome (see this term), variable developmental delay and facial dysmorphism.
Epidemiology
It has been clinically and molecularly characterized in 3 patients.
Clinical description
Dysmorphic features include macrocephaly, hypertelorism, down-slanting palpebral fissures and microstomia.
Etiology
This syndrome is caused by an interstitial deletion encompassing 20p12.3. All these deletions except one occurred de novo and were characterized by comparative genomic hybridization (CGH) microarray and fluorescence in situ hybridization (FISH). They have a variable size with the smallest region of overlap including only one gene, BMP2, which is a good candidate gene for explaining the phenotype of Wolff-Parkinson-White syndrome.

                            Last update: 
                            June 2011


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
20p13 microdeletion syndrome (ORPHA:313781)
20p13 microdeletion syndrome is a rare chromosomal anomaly characterized by developmental delay, mild to moderate intellectual disability, epilepsy, and unspecific dysmorphic signs. High palate, delayed permanent tooth eruption, hypoplastic fingernails, clinodactyly and short fingers have also been reported.
20q11.2 microdeletion syndrome (ORPHA:444051)
A rare, genetic, syndromic intellectual disability characterized by psychomotor delay, hypotonia, feeding difficulties, failure to thrive, anomalies of the hands and feet (clinodactyly, camptodactyly, brachydactyly, feet malposition), and craniofacial dysmorphism. Associated prenatal growth retardation, and gastrointestinal, heart and eye anomalies have been reported.
20q11.2 microduplication syndrome (ORPHA:363659)
20q11.2 microduplication syndrome is a rare chromosomal anomaly syndrome, due to partial duplication of the long arm of chromosome 20, characterized by psychomotor and developmental delay, moderate intellectual disability, metopic ridging/trigonocephaly, short hands and/or feet and distinctive facial features (epicanthus, hypoplastic supraorbital ridges, horizontal/downslanting palpebral fissures, small nose with depressed nasal bridge and anteverted nostrils, prominent cheeks, retrognathia and small, thick ears). Growth delay and cryptororchidism are often associated features.
20q13.33 microdeletion syndrome (ORPHA:261311)
A rare chromosomal anomaly syndrome resulting from the partial deletion of the long arm of chromosome 20 with a highly variable phenotype typically characterized by hypotonia, intellectual disability, cognitive and language deficits (including decreased or absent speech), pre and post-natal growth retardation, feeding difficulties, microcephaly, and malformed hands and feet. Neurodevelopmental disorders (including hyperactivity, social interactive problems and autism spectrum disorder), seizures and dysmorphic facial features (high forehead, hypertelorism, malformed ears, broad nasal bridge, bulbous nasal tip, thin upper lip, small chin) are frequently associated.
21q22.11q22.12 microdeletion syndrome (ORPHA:261323)
A rare, genetic, chromosomal anomaly syndrome resulting from a partial deletion of the long arm of chromosome 21 characterized by pre- and post-natal growth delay, short stature, intellectual disability, developmental delay with severe language impairment, thrombocytopenia, and craniofacial dysmorphism which may include microcephaly, downslanted palpebral ﬁssures, low-set ears, broad nose, thin upper vermillion, and downturned corners of the mouth. Brain MRI abnormalities (such as agenesis of the corpus callosum), behavioral problems and seizures may be associated.
2p13.2 microdeletion syndrome (ORPHA:363680)
A rare partial autosomal monosomy characterized by global development delay, intellectual disability, behavioral abnormalities (hyperactivity, attention deficit and autistic behaviors), brachycephaly and variable facial dysmorphism. Other associated features may include vertebral fusions, mild contractures of knees and elbows, and feeding difficulties during infancy.
2p15p16.1 microdeletion syndrome (ORPHA:261349)
2p15p16.1 microdeletion syndrome is a recently described syndrome characterized by developmental delay and facial dysmorphism.
Epidemiology
It has been clinically and molecularly characterized in 5 patients.
Clinical description
Dysmorphic features include receding forehead, telecanthus, epicanthic fold, short and down-slanting palpebral fissures, ptosis, broad and high nasal bridge, retrognathia, flat philtrum, small mouth with high, narrow palate and everted lower lip. Ophthalmologic examination in 4 patients revealed bilateral optic atrophy/hypoplasia. Microcephaly, short stature, genitourinary abnormalities and behavioral problems are common.
Etiology
This syndrome is caused by an interstitial deletion 2p15p16.1 (present in mosaic in one patient). These de novo deletions were characterized by comparative genomic hybridisation (CGH) microarray and fluorescence in situ hybridization (FISH). They have a variable size from 570 kb to 5.7 Mb and encompass several genes. Haploinsufficiency of these genes could contribute to the phenotype.

                            Last update: 
                            June 2011
2p21 microdeletion syndrome without cystinuria (ORPHA:369881)
2p21 microdeletion syndrome without cystinuria is a rare partial autosomal monosomy characterized by weak fetal movements, severe infantile hypotonia and feeding difficulties that spontaneously improve with time, urogenital abnormalities (hypospadias or hypoplastic labia majora), global development delay, mild intellectual disability and facial dysmorphism (dolichocephaly, frontal bossing, bilateral ptosis, midface retrusion, open mouth with tented upper lip vermilion). Affected individuals have borderline elevated serum lactate but no cystinuria.
2p21 microdeletion syndrome (ORPHA:163693)
The 2p21 microdeletion syndrome consists of cystinuria, neonatal seizures, hypotonia, severe growthand developmental delay, facial dysmorphism, and lactic acidemia.
Epidemiology
It has been described in seven patients from three families of a small Bedouin clan.
Clinical description
Dysmorphic features include frontal bossing, almond-shaped eyes, long eyelashes, depressed nasal bridge, and large, posteriorly rotated ears. Renal lithiasis occurs at an early age in all patients. Reduced activity of the respiratory chain complexes I, III, IV and V was found in patients examined.
Etiology
The syndrome is caused by homozygous deletion of at least four contiguous genes on chromosome 2: SLC3A1, PREPL, PPM1B and C2orf34 (2p21).

                            Last update: 
                            November 2010
2q23.1 microdeletion syndrome (ORPHA:228402)
The newly described 2q23.1 microdeletion syndrome includes severe intellectual deficit with pronounced speech delay, behavioral abnormalities including hyperactivity and inappropriate laughter, short stature and seizures.
Epidemiology
To date, fifteen patients have been reported.
Clinical description
Dysmorphic features include microcephaly, wide and open mouth, a tented upper lip, and prominent incisors. The majority of cases present with stereotypic repetitive behavior, a disturbed sleep pattern and a broad-based gait. Skeletal abnormalities include generalized brachydactyly with small hands and feet.
Etiology
The microdeletion was identified by microarray based comparative genomic hybridization (aCGH). The size of the deletions is variable; the critical region includes a single gene, MBD5. Another gene, EPC2, is deleted in patients who have a broader phenotype than those with a deletion of MBD5 only.

                            Last update: 
                            May 2010


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
2q23.1 microduplication syndrome (ORPHA:313947)
2q23.1 microduplication syndrome is a rare chromosomal anomaly syndrome, resulting from the partial duplication of the long arm of chromosome 2, primarily characterized by global developmental delay, hypotonia, autistic-like features and behavioural problems. Craniofacial dysmorphism (arched eyebrows, hypertelorism, bilateral ptosis, prominent nose, wide mouth, micro/retrognathia) and an affable personality are also commonly associated. Minor digital anomalies (fifth finger clinodactyly and large, broad first toe) have occasionally been reported.
2q31.1 microdeletion syndrome (ORPHA:251014)
2q31.1 microdeletion syndrome is a well-defined and clinically recognisable syndrome characterized by moderate to severe developmental delay, short stature, facial dysmorphism and variable limb defects.
Epidemiology
It has been reported in 20 patients.
Clinical description
Dysmorphic features include microcephaly, downslanting palpebral fissures, flat and long philtrum, micrognathia and low-set and dysplastic ears. The spectrum of limb defects ranges from monodactylous ectrodactyly, brachydactyly and syndactyly to camptodactyly. The lower limbs tend to be more often and more severely affected than the upper limbs.
Etiology
This microdeletion was identified by comparative genomic hybridization (CGH) microarray and its size is variable. The critical region encompasses the HOXD genes, haploinsufficiency of which results in the skeletal phenotype.

                            Last update: 
                            March 2011


                            - Expert reviewer(s): 
                            Dr Nicole MORICHON-DELVALLEZ
2q32q33 microdeletion syndrome (ORPHA:251019)
A rare autosomal monosomy characterized by a variable phenotype with moderate to severe intellectual disability, behavioral problems, short stature, microcephaly, dysplastic nails, sparse hair, cleft palate and dysmorphic craniofacial features.
3-hydroxy-3-methylglutaryl-CoA synthase deficiency (ORPHA:35701)
3-hydroxy-3-methylglutaryl-CoA synthase deficiency (HMG-CoA synthase deficiency) is a rare autosomal recessively inherited disorder of ketone body metabolism (see this term), reported in less than 20 patients to date, characterized clinically by episodes of decompensation (often associated with gastroenteritis or fasting) that present with vomiting, lethargy, hepatomegaly, non ketotic hypoglycemia and, in rare cases, coma. Patients are mostly asymptomatic between acute epidodes. HMG-CoA synthase deficiency requires an early diagnosis in order to avoid hypoglycemic crises that can lead to permanent brain damage or death.