TABLE 2.
Genotype–phenotype correlations of patients with developmental delay/intellectual disability without congenital structural anomalies, compared with the family described by Willemsen et al. (2014)
| Patient 9 | Patient 10 | Patient 11 | Willemsen et al. family | |
|---|---|---|---|---|
| Gender | M | M | M | M |
| Ethnicities/Country of origin | Caucasian | Caucasian | Hispanic, Mexican, and Guatemalan ancestry | Caucasian |
| Age of examination | 9 years | 16 years | 2 years 9 months | Five affected males across three generations, specific ages not given |
| Prenatal history | Unremarkable | IUGR and placental insufficiency | Unremarkable | Unremarkable |
| Brain anomaly | Normal MRI at 9 years | Mild ventriculomegaly at birth, normal MRI at 15 years | Normal MRI at 3 years | Central atrophy of lateral hemispheres (III: 7 at age 53) and wide posterior horns (IV: 3 at age 7) |
| Eye anomaly | Not present | Retinopathy related to disease‐causing GPR143 variant (rs137852297) | Not present | Not present |
| Skeletal anomalies | Not present | Delay of osseous age; Perthes disease involving right hip | Not present | Not present |
| Other malformations | Not present | Cryptorchidism; Pelvic left kidney | Not present | Not present |
| Intellectual development | Intellectual disability, speech delay | Borderline intellectual functioning, speech delay, attention deficit, anxiety disturbance, depressive traits. | Intellectual disability, speech delay | Intellectual disability, speech delay |
| Motor development | Not present | Motor delay | Motor delay | ? |
| Global developmental delay | + | + | + | + |
| Autism spectrum disorder | + | Not present | + | Not present |
| Seizures | Not present | Not present | Isolated febrile seizure at 2 years of age | 4/5, developed in late childhood–adolescence, complex partial and generalized, absence and tonic–clonic |
| Other clinical features | Not present | Not present | Dysmorphic features including relative macrocephaly, upslanting palpebral fissures, prominent cupped ears, large forehead, plagiocephaly | Mild, nonspecific facial dysmorphisms |
| Variant description | c.1745T>A, p.(Leu582His) Hemizygous | c.2558G>T, p.(Arg853Leu) Hemizygous | c.3299G>A, p.(Arg1100 Lys) Hemizygous | c.1489‐8_delins10, Hemizygous |
| Inheritance | Maternal | Maternal | Maternal | Maternal |
| Other genetic findings | Chromosomal microarray: 13q31.3 duplication (93,281,466‐94,095,389x3), classified as a CNV of unclear significance by GeneDx, found to be maternally inherited. | Normal karyotype, chromosomal microarray, Methylation at IGF2‐H19, IC1 loci | Normal chromosomal microarray and FMR1 | Normal karyotyping, DNA analysis of FMR1 and ARX genes |
| Family history | Mother has history of anxiety and depression. | Unremarkable | Unremarkable | Five affected males across three generations |