Congenital malformations, deformations and chromosomal abnormalities
Other congenital malformations
Autosomal recessive
22q11.21
Mental retardation is a leading feature of many mendelian syndromes. In addition, studies in mental institutions show that mental retardation of unclassified type occurs in multiple sibs in a considerable number of cases. Some of these doubtless represent rare recessive disorders. [From OMIM]
| Subject ID | Country | Sex | Family History | Parental Consanguinity | HPO Terms | Variant | Zygosity | Mode of Inheritance | Reference | Remarks |
|---|---|---|---|---|---|---|---|---|---|---|
| 600237.1 | Saudi Arabia | Male | No | Yes | Global developmental delay; Severe postn... Global developmental delay; Severe postnatal growth retardation; Strabismus; Cryptorchidism; Hirsutism; Scoliosis; Abnormality of brain morphology; Abnormal facial shape  | NM_003325.4:c.41A>G | Homozygous | Autosomal, Recessive | Anazi et al. 2017a | |
| 604020.1 | Jordan | Male | No | Yes | Intellectual disability; Macrocephaly; A... Intellectual disability; Macrocephaly; Astigmatism; Short stature; Strabismus | NM_003458.4:c.10988G>T, NM_003458.4:c.11489G>A | Compound heterozygous | Autosomal, Recessive | Froukh. 2017 | |
| 611251.1.1 | Jordan | Male | Yes | Yes | Intellectual disability, mild; Seizure; ... Intellectual disability, mild; Seizure; Delayed gross motor development | NM_020780.2:c.3555C>T | Homozygous | Autosomal, Recessive | Froukh. 2017 | |
| 611251.1.2 | Jordan | Male | Yes | Yes | Intellectual disability, mild; Seizure Intellectual disability, mild; Seizure | NM_020780.2:c.3555C>T | Homozygous | Autosomal, Recessive | Froukh. 2017 | Sibling of 611251.1.... |
| 611251.1.3 | Jordan | Male | Yes | Yes | Intellectual disability, mild; Seizure; ... Intellectual disability, mild; Seizure; Delayed gross motor development; Delayed speech and language development | NM_020780.2:c.3555C>T | Homozygous | Autosomal, Recessive | Froukh. 2017 | Sibling of 611251.1.... |
| 612830.1 | Jordan | Female | Yes | Intellectual disability; Motor delay; Ag... Intellectual disability; Motor delay; Aggressive behavior | NM_004753.7:c.328G>A | Homozygous | Autosomal, Recessive | Has three similarly ... | ||
| 613610.1.1 | Saudi Arabia | Female | Yes | Yes | Strabismus; Renal insufficiency; Hepatic... Strabismus; Renal insufficiency; Hepatic fibrosis; Global developmental delay; Depressed nasal bridge; Cerebellar atrophy | NM_001013663.2:c.365G>A | Homozygous | Autosomal, Recessive | Maddirevula et al. 2018; Maddirevula et al. 2020 | |
| 613610.1.2 | Saudi Arabia | Female | Yes | Yes | Strabismus; Renal insufficiency; Hepatic... Strabismus; Renal insufficiency; Hepatic fibrosis; Global developmental delay | NM_001013663.2:c.365G>A | Homozygous | Autosomal, Recessive | Maddirevula et al. 2018; Maddirevula et al. 2020 | Sister of 613610.1.1 |
| 617342.1.1 | Saudi Arabia | Female | Yes | Yes | Intellectual disability; Global developm... Intellectual disability; Global developmental delay; Hypotonia; Hyperactivity; Absent speech; Abnormal facial shape | NM_001013663.2:c.365G>A | Homozygous | Autosomal, Recessive | Maddirevula et al. 2020 | |
| 617342.1.2 | Saudi Arabia | Male | Yes | Yes | Intellectual disability; Hyperactivity; ... Intellectual disability; Hyperactivity; Abnormal facial shape; Global developmental delay; Delayed speech and language development; Bilateral tonic-clonic seizure | NM_001013663.2:c.365G>A | Homozygous | Autosomal, Recessive | Maddirevula et al. 2020 | Brother of 617342.1.... |
| 617342.1.3 | Saudi Arabia | Male | Yes | Yes | Intellectual disability; Hyperactivity; ... Intellectual disability; Hyperactivity; Global developmental delay; Delayed speech and language development; Bilateral tonic-clonic seizure | NM_001013663.2:c.365G>A | Homozygous | Autosomal, Recessive | Maddirevula et al. 2020 | Brother of 617342.1.... |
| 617342.2.1 | Saudi Arabia | Male | Yes | Yes | Intellectual disability; Aggressive beha... Intellectual disability; Aggressive behavior | NM_001013663.2:c.365G>A | Homozygous | Autosomal, Recessive | Maddirevula et al. 2020 | |
| 617342.2.2 | Saudi Arabia | Female | Yes | Yes | Intellectual disability Intellectual disability | NM_001013663.2:c.365G>A | Homozygous | Autosomal, Recessive | Maddirevula et al. 2020 | Sister of 617342.2.1 |
Megarbane et al. 2002d reported on monozygotic twin brothers exhibiting intellectual disability, short stature, macrocephaly, brachydactyly, clinodactyly, cryptorchidism, and prelingual sensorineural deafness. One of the brothers passed away from a cradiac arrest following acute respiratory infection. A cryptic chromosomal rearrangement involving a partial 6p trisomy and partial 11q monosomy was identified in the surviving brother. The father exhibited a balanced reciprocal translocation.
Delague et al. 2006 screened for subtelomeric rearrangements in 45 patients from 34 independent families, exhibiting intellectual disability with normal karyotype and negative biochemical tests. The patients exhibited one or more of the following: growth abnormalities, dysmorphic features, and/or malformations. 85 fluorescently labelled STR markers were genotyped in each patient and their parents. 5 cryptic rearrangements were identified, 3 of which were confirmed using FISH.
Haddad et al. 2009 reported on a female patient with mild intellectual disability and dysmorphic features. A de novo balanced translocation t(5;18)(q21.3;q21.32) was identified in the patient. The tyrosine kinase gene FER was identified as a candidate gene at the translocation break point; however molecular analysis and RT-qPCR showed that the gene was uninterrupted by the break and showed no modififed expression in lymphoblastoid cell cultures.
Makrythanasis et al. (2014) studied 50 families using WES analysis to diagnose patients with recessive disorders. The cohort included a Lebanese family with syndromic ID and developmental delay and another with syndromic ID and neurological deficit.
Choucair et al. (2015) studied a cohort of 149 Lebanese patients with Intellectual disability or develomental delay and identified a total of 20 pathogenic and six likely pathogenic CNVs.