Entry - #616078 - INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 29; MRD29 - OMIM

 
ICD+
# 616078

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 29; MRD29


Alternative titles; symbols

MENTAL RETARDATION, AUTOSOMAL DOMINANT 29


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
18q12.3 Intellectual developmental disorder, autosomal dominant 29 616078 AD 3 SETBP1 611060
Clinical Synopsis
 
Phenotypic Series
 

INHERITANCE
- Autosomal dominant
HEAD & NECK
Head
- Brachycephaly
- Dolichocephaly
Face
- Dysmorphic facies, variable
- Long face
- Pointed chin
Ears
- Low-set ears
Eyes
- Downslanting palpebral fissures
- Hypertelorism
- Ptosis
- Synophrys
Nose
- Full nasal tip
Mouth
- High palate
- Narrow palate
- Thin upper lip
Teeth
- Crowded teeth
NEUROLOGIC
Central Nervous System
- Impaired intellectual development, mild to moderate (IQ 30-76)
- Delayed speech
- Absent speech
- Delayed motor development
- Seizures (uncommon)
Behavioral Psychiatric Manifestations
- Attention deficit hyperactivity disorder
MISCELLANEOUS
- Variable dysmorphic features
MOLECULAR BASIS
- Caused by mutation in the SET-binding protein 1 gene (SETBP1, 611060.0006)
▲ Close
Intellectual developmental disorder, autosomal dominant - PS156200 - 66 Entries
Location Phenotype Inheritance Phenotype
mapping key 		Phenotype
MIM number 		Gene/Locus Gene/Locus
MIM number
1p36.11 Coffin-Siris syndrome 2 AD 3 614607 ARID1A 603024
1q21.3 White-Sutton syndrome AD 3 616364 POGZ 614787
1q21.3 GAND syndrome AD 3 615074 GATAD2B 614998
1q22 Intellectual developmental disorder, autosomal dominant 52 AD 3 617796 ASH1L 607999
1q44 Intellectual developmental disorder, autosomal dominant 22 AD 3 612337 ZBTB18 608433
2p25.3 Intellectual developmental disorder, autosomal dominant 39 AD 3 616521 MYT1L 613084
2q11.2 ?Intellectual developmental disorder, autosomal dominant 69 3 617863 LMAN2L 609552
2q23.1 Intellectual developmental disorder, autosomal dominant 1 AD 3 156200 MBD5 611472
3p25.3 Intellectual developmental disorder, autosomal dominant 23 AD 3 615761 SETD5 615743
3p21.31 Intellectual developmental disorder, autosomal dominant 70 AD 3 620157 SETD2 612778
3q22.3 Intellectual developmental disorder, autosomal dominant 47 AD 3 617635 STAG1 604358
3q26.32 Intellectual developmental disorder, autosomal dominant 41 AD 3 616944 TBL1XR1 608628
3q27.1 Intellectual developmental disorder 60 with seizures AD 3 618587 AP2M1 601024
4q31.1 Intellectual developmental disorder, autosomal dominant 50, with behavioral abnormalities AD 3 617787 NAA15 608000
5p15.2 Intellectual developmental disorder, autosomal dominant 63, with macrocephaly AD 3 618825 TRIO 601893
5p15.2 Intellectual developmental disorder, autosomal dominant 44, with microcephaly AD 3 617061 TRIO 601893
5q13.3 Intellectual developmental disorder, autosomal dominant 34 AD 3 616351 COL4A3BP 604677
5q32 Intellectual developmental disorder, autosomal dominant 53 AD 3 617798 CAMK2A 114078
5q33.2 Intellectual developmental disorder, autosomal dominant 67 AD 3 619927 GRIA1 138248
6p21.32 Intellectual developmental disorder, autosomal dominant 5 AD 3 612621 SYNGAP1 603384
6q13 Intellectual developmental disorder, autosomal dominant 46 AD 3 617601 KCNQ5 607357
6q14.3 Intellectual developmental disorder, autosomal dominant 64 AD 3 619188 ZNF292 616213
6q22.1 Intellectual developmental disorder, autosomal dominant 55, with seizures AD 3 617831 NUS1 610463
6q24.2 Intellectual developmental disorder, autosomal dominant 43 AD 3 616977 HIVEP2 143054
6q25.3 Coffin-Siris syndrome 1 AD 3 135900 ARID1B 614556
7p22.1 Intellectual developmental disorder, autosomal dominant 48 AD 3 617751 RAC1 602048
7p13 Intellectual developmental disorder, autosomal dominant 54 AD 3 617799 CAMK2B 607707
7q11.22 Intellectual developmental disorder, autosomal dominant 26 AD 3 615834 KIAA0442 607270
7q36.2 Intellectual developmental disorder, autosomal dominant 33 AD 3 616311 DPP6 126141
9p24 Intellectual developmental disorder, autosomal dominant 2 AD 4 614113 MRD2 614113
9q34.11 Intellectual developmental disorder, autosomal dominant 58 AD 3 618106 SET 600960
9q34.3 Kleefstra syndrome 1 AD 3 610253 EHMT1 607001
10p15.3 Intellectual developmental disorder, autosomal dominant 30 AD 3 616083 ZMYND11 608668
10q22.2 Intellectual developmental disorder, autosomal dominant 59 AD 3 618522 CAMK2G 602123
11p15.5 Vulto-van Silfout-de Vries syndrome AD 3 615828 DEAF1 602635
11q13.1 Coffin-Siris syndrome 7 AD 3 618027 DPF2 601671
11q13.1-q13.2 Schuurs-Hoeijmakers syndrome AD 3 615009 PACS1 607492
11q13.2 Intellectual developmental disorder, autosomal dominant 51 AD 3 617788 KMT5B 610881
11q24.2 Intellectual developmental disorder, autosomal dominant 4 AD 2 612581 MRD4 612581
12p13.1 Intellectual developmental disorder, autosomal dominant 6, with or without seizures AD 3 613970 GRIN2B 138252
12q12 Coffin-Siris syndrome 6 AD 3 617808 ARID2 609539
12q13.12 Intellectual developmental disorder, autosomal dominant, FRA12A type AD 3 136630 DIP2B 611379
12q13.2 Coffin-Siris syndrome 8 AD 3 618362 SMARCC2 601734
12q21.33 Intellectual developmental disorder, autosomal dominant 66 AD 3 619910 ATP2B1 108731
14q11.2 Intellectual developmental disorder, autosomal dominant 74 AD 3 620688 HNRNPC 164020
15q21.3 Intellectual developmental disorder, autosomal dominant 71, with behavioral abnormalities AD 3 620330 RFX7 612660
16p13.3 Intellectual developmental disorder, autosomal dominant 72 AD 3 620439 SRRM2 606032
16q22.1 Intellectual developmental disorder, autosomal dominant 21 AD 3 615502 CTCF 604167
16q24.3 Intellectual developmental disorder, autosomal dominant 3 AD 3 612580 CDH15 114019
17p13.1 Intellectual developmental disorder, autosomal dominant 62 AD 3 618793 DLG4 602887
17q21.2 Coffin-Siris syndrome 5 AD 3 616938 SMARCE1 603111
17q21.31 Koolen-De Vries syndrome AD 3 610443 KANSL1 612452
17q23.1 Intellectual developmental disorder, autosomal dominant 56 AD 3 617854 CLTC 118955
17q23.2 Intellectual developmental disorder, autosomal dominant 61 AD 3 618009 MED13 603808
17q23.2 Intellectual developmental disorder, autosomal dominant 57 AD 3 618050 TLK2 608439
18q12.3 Intellectual developmental disorder, autosomal dominant 29 AD 3 616078 SETBP1 611060
19p13.3 Intellectual developmental disorder, autosomal dominant 65 AD 3 619320 KDM4B 609765
19p13.2 Coffin-Siris syndrome 4 AD 3 614609 SMARCA4 603254
19q13.12 Intellectual developmental disorder, autosomal dominant 68 AD 3 619934 KMT2B 606834
19q13.2 Intellectual developmental disorder, autosomal dominant 45 AD 3 617600 CIC 612082
20q11.23 ?Intellectual developmental disorder, autosomal dominant 11 AD 3 614257 EPB41L1 602879
20q13.33 Intellectual developmental disorder, autosomal dominant 73 AD 3 620450 TAF4 601796
20q13.33 Intellectual developmental disorder, autosomal dominant 38 AD 3 616393 EEF1A2 602959
21q22.13 Intellectual developmental disorder, autosomal dominant 7 AD 3 614104 DYRK1A 600855
22q11.23 Coffin-Siris syndrome 3 AD 3 614608 SMARCB1 601607
22q12.3 ?Intellectual developmental disorder, autosomal dominant 10 AD 3 614256 CACNG2 602911
▲ Close

▼ TEXT

A number sign (#) is used with this entry because of evidence that autosomal dominant intellectual developmental disorder-29 (MRD29) is caused by heterozygous mutation in the SETBP1 gene (611060) on chromosome 18q12.

▼ Clinical Features

Coe et al. (2014) reported 9 patients, including 1 reported by Rauch et al. (2012), with frameshift or nonsense mutations in SETBP1 who had a cognitive phenotype ranging from normal with impaired speech to profound intellectual disability (ID). The majority of patients had speech and motor delays, mild dysmorphic features, and behavioral difficulties. Two of the patients had seizures or EEG abnormalities. In addition, the authors reported 1 patient with a deletion encompassing the SETBP1 gene. Coe et al. (2014) also reported on 1 patient studied by Marseglia et al. (2012) and 2 patients studied by Filges et al. (2011). These patients had mild or moderate ID, speech and motor delays, and facial dysmorphisms. Two of the 3 patients had seizures or EEG abnormalities. In patients positive for mutation in SETBP1, Coe et al. (2014) observed a dysmorphism typified by a long face, characteristic eyebrows, and, in a few patients, low-set ears and cafe-au-lait spots. In 7 of 13 patients for whom brain MRI was available, no abnormalities were found; in 1 additional patient, MRI showed no major anomalies but minimal signal of the peritrigonal white matter.


▼ Molecular Genetics

Coe et al. (2014) created an expanded copy number variant (CNV) morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. They then resequenced 26 candidate genes in 4,716 additional cases with developmental delay or autism and 2,193 controls. An integrated analysis of CNV and single-nucleotide variant (SNV) data pinpointed 10 genes enriched for putative loss of function. Among these was SETBP1, haploinsufficiency of which was associated with intellectual disability and loss of expressive language. Coe et al. (2014) reported 4 nonsense mutations in SETBP1 (e.g., 611060.0007), 2 of which were confirmed to be de novo, as well as 4 frameshift mutations (e.g., 611060.0006), of which 1 was confirmed to be de novo.


▼ REFERENCES

  1. Coe, B. P., Witherspoon, K., Rosenfeld, J. A., van Bon, B. W. M., Vulto-van Silfhout, A. T., Bosco, P., Friend, K. L., Baker, C., Buono, S., Vissers, L. E. L. M., Schuurs-Hoeijmakers, J. H., Hoischen, A., and 26 others. Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nature Genet. 46: 1063-1071, 2014. [PubMed: 25217958, images, related citations] [Full Text]

  2. Filges, I., Shimojima, K., Okamoto, N., Rothlisberger, B., Weber, P., Huber, A. R., Nishizawa, T., Datta, A. N., Miny, P., Yamamoto, T. Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome. J. Med. Genet. 48: 117-122, 2011. [PubMed: 21037274, related citations] [Full Text]

  3. Marseglia, G., Scordo, M. R., Pescucci, C., Nannetti, G., Biagini, E., Scandurra, V., Gerundino, F., Magi, A., Benelli, M., Torricelli, F. 372 kb microdeletion in 18q12.3 causing SETBP1 haploinsufficiency associated with mild mental retardation and expressive speech impairment. Europ. J. Med. Genet. 55: 216-221, 2012. [PubMed: 22333924, related citations] [Full Text]

  4. Rauch, A., Wieczorek, D., Graf, E., Wieland, T., Endele, S., Schwarzmayr, T., Albrecht, B., Bartholdi, D., Beygo, J., Di Donato, N., Dufke, A., Cremer, K., and 27 others. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 380: 1674-1682, 2012. [PubMed: 23020937, related citations] [Full Text]


Creation Date:
Ada Hamosh : 10/30/2014
Edit History:
alopez : 04/06/2022
alopez : 06/28/2017
carol : 11/05/2014
alopez : 10/30/2014

# 616078

INTELLECTUAL DEVELOPMENTAL DISORDER, AUTOSOMAL DOMINANT 29; MRD29


Alternative titles; symbols

MENTAL RETARDATION, AUTOSOMAL DOMINANT 29


ORPHA: 436151;   DO: 0070059;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number 		Inheritance Phenotype
mapping key 		Gene/Locus Gene/Locus
MIM number
18q12.3 Intellectual developmental disorder, autosomal dominant 29 616078 Autosomal dominant 3 SETBP1 611060

TEXT

A number sign (#) is used with this entry because of evidence that autosomal dominant intellectual developmental disorder-29 (MRD29) is caused by heterozygous mutation in the SETBP1 gene (611060) on chromosome 18q12.

Clinical Features

Coe et al. (2014) reported 9 patients, including 1 reported by Rauch et al. (2012), with frameshift or nonsense mutations in SETBP1 who had a cognitive phenotype ranging from normal with impaired speech to profound intellectual disability (ID). The majority of patients had speech and motor delays, mild dysmorphic features, and behavioral difficulties. Two of the patients had seizures or EEG abnormalities. In addition, the authors reported 1 patient with a deletion encompassing the SETBP1 gene. Coe et al. (2014) also reported on 1 patient studied by Marseglia et al. (2012) and 2 patients studied by Filges et al. (2011). These patients had mild or moderate ID, speech and motor delays, and facial dysmorphisms. Two of the 3 patients had seizures or EEG abnormalities. In patients positive for mutation in SETBP1, Coe et al. (2014) observed a dysmorphism typified by a long face, characteristic eyebrows, and, in a few patients, low-set ears and cafe-au-lait spots. In 7 of 13 patients for whom brain MRI was available, no abnormalities were found; in 1 additional patient, MRI showed no major anomalies but minimal signal of the peritrigonal white matter.


Molecular Genetics

Coe et al. (2014) created an expanded copy number variant (CNV) morbidity map from 29,085 children with developmental delay in comparison to 19,584 healthy controls, identifying 70 significant CNVs. They then resequenced 26 candidate genes in 4,716 additional cases with developmental delay or autism and 2,193 controls. An integrated analysis of CNV and single-nucleotide variant (SNV) data pinpointed 10 genes enriched for putative loss of function. Among these was SETBP1, haploinsufficiency of which was associated with intellectual disability and loss of expressive language. Coe et al. (2014) reported 4 nonsense mutations in SETBP1 (e.g., 611060.0007), 2 of which were confirmed to be de novo, as well as 4 frameshift mutations (e.g., 611060.0006), of which 1 was confirmed to be de novo.


REFERENCES

  1. Coe, B. P., Witherspoon, K., Rosenfeld, J. A., van Bon, B. W. M., Vulto-van Silfhout, A. T., Bosco, P., Friend, K. L., Baker, C., Buono, S., Vissers, L. E. L. M., Schuurs-Hoeijmakers, J. H., Hoischen, A., and 26 others. Refining analyses of copy number variation identifies specific genes associated with developmental delay. Nature Genet. 46: 1063-1071, 2014. [PubMed: 25217958] [Full Text: https://doi.org/10.1038/ng.3092]

  2. Filges, I., Shimojima, K., Okamoto, N., Rothlisberger, B., Weber, P., Huber, A. R., Nishizawa, T., Datta, A. N., Miny, P., Yamamoto, T. Reduced expression by SETBP1 haploinsufficiency causes developmental and expressive language delay indicating a phenotype distinct from Schinzel-Giedion syndrome. J. Med. Genet. 48: 117-122, 2011. [PubMed: 21037274] [Full Text: https://doi.org/10.1136/jmg.2010.084582]

  3. Marseglia, G., Scordo, M. R., Pescucci, C., Nannetti, G., Biagini, E., Scandurra, V., Gerundino, F., Magi, A., Benelli, M., Torricelli, F. 372 kb microdeletion in 18q12.3 causing SETBP1 haploinsufficiency associated with mild mental retardation and expressive speech impairment. Europ. J. Med. Genet. 55: 216-221, 2012. [PubMed: 22333924] [Full Text: https://doi.org/10.1016/j.ejmg.2012.01.005]

  4. Rauch, A., Wieczorek, D., Graf, E., Wieland, T., Endele, S., Schwarzmayr, T., Albrecht, B., Bartholdi, D., Beygo, J., Di Donato, N., Dufke, A., Cremer, K., and 27 others. Range of genetic mutations associated with severe non-syndromic sporadic intellectual disability: an exome sequencing study. Lancet 380: 1674-1682, 2012. [PubMed: 23020937] [Full Text: https://doi.org/10.1016/S0140-6736(12)61480-9]


Creation Date:
Ada Hamosh : 10/30/2014

Edit History:
alopez : 04/06/2022
alopez : 06/28/2017
carol : 11/05/2014
alopez : 10/30/2014



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OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2024 Johns Hopkins University.

NOTE: OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine. While the OMIM database is open to the public, users seeking information about a personal medical or genetic condition are urged to consult with a qualified physician for diagnosis and for answers to personal questions.
OMIM® and Online Mendelian Inheritance in Man® are registered trademarks of the Johns Hopkins University.
Copyright® 1966-2024 Johns Hopkins University.
Printed: April 25, 2024