Clinical features, factor VIII levels and chromosome X-inactivation results for subjects with int22h-1/int22h-2-mediated Xq28 duplications and deletions
| ID | Facial features | Behavioural abnormalities | Other clinical manifestations | FVIII (%) | Chromosome X-inactivation | ||||
| AR locus | FMR1 locus | ||||||||
| Allele size (nt) | Ratio | Allele size (nt) | Ratio | ||||||
| Xq28 duplication | |||||||||
| Family 1 | |||||||||
| Older brother 11 years | + | High forehead, long face, upper eyelid fullness, open mouth, thick lower lip, narrow high arch palate, teeth crowding and overbite (figure 1A). | Asperger syndrome, aggressive behaviours and difficulty sleeping. | Recurrent pneumonias and ear infections, nosebleed, reactive airway disease and toe-walking. | 124 | 248 | NA | 281 | NA |
| Younger brother 3 years | + | High forehead, upper eyelid fullness, broad nasal bridge, sparse eyebrows, small ears with simple helices, thick lower lip and tongue tie with lingual frenulum (figure 1B) | – | Bilateral metatarsus adductus, recurrent ear infections, hearing loss, and patent foramen ovale and ductus arteriosus. | 286 | 248 | NA | 380 | NA |
| Mother 32 years | + | High forehead, broad nasal bridge, sparse eyebrows and thick lower lip (figure 1C). | – | – | NA | 239 /248 | 89:11 | 281/380 | 13:87 |
| Family 2 | |||||||||
| Son 3 years | + | High forehead, upper eyelid fullness, deep-seated eyes, broad nasal bridge, thick lower lip and retrognathia (figure 1D). | Hyperactivity and aggression. | Pneumonia and recurrent ear infections. | 268 | 242 | NA | 278 | NA |
| Mother 19 years | + | NA | NA | NA | NA | 242/254 | 12:88 | 278/308 | 13:87 |
| Family 3 | |||||||||
| Son 15 years | + | High forehead, upper eyelid fullness, deep-seated eyes, broad nasal bridge and retrognathia (figure 1E). | Motor tics, anxiety and attention deficit hyperactivity disorder. | Recurrent ear infections, asthma, allergic rhinitis, joint pains, mild proximal muscle weakness, hypotonia, flat feet, recurrent nosebleed, easy bruising and prolonged bleeding. | 24 | 242 | NA | 314 | NA |
| Mother 41 years | + | NA | Depression. | Hypothyroidism. | NA | 242/242 | NI | 308/314 | 6:94 |
| Xq28 deletion | |||||||||
| Family 4 | |||||||||
| Daughter 6 years | – | High forehead (figure 1F). | Hyperactivity, inattentive, impulsiveness, stereotypic movements and sensory integration difficulties. | Clinodactyly and café-au-lait spot. | 60 | 254/257 | 0:100 | Not done | NA |
| Mother 39 years | – | NA | – | NA | NA | 233/257 | 0:100 | Not done | NA |
The preferentially inactive alleles in females are in bold.
Chromosome X-inactivation assays were performed at the AR (androgen receptor) and FMR1 (fragile X mental retardation 1) loci.
ID, intellectual disability or developmental delay; FVIII, factor VIII levels with normal range 50%–200%; NA, not available or applicable; NI, non-informative; nt, nucleotides.