Table 1 Deep dysmorphological phenotyping after clinical evaluation of the 5 patients presented here
Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Total | |
|---|---|---|---|---|---|---|
Variant’s genomic position | 8:41792353 | 8:41792098 | 8:41792310 | 8:41834814 | 8:41791480 | |
cDNA change | c.3385C > T | c.3640A > T | c.3427_3428insTA | c.1075G > A | c.4254_4257 delTGAG | |
Protein change | p.(Arg1129*) | p.(Lys1214*) | p.(Ser1143 Leufs*5) | p.Gly359Ser (p.Pro509 Thrfs*11) | p.(Glu1419 Trpfs*12) | |
Exon | 17/17 | 17/17 | 17/17 | 7/17 | 17/17 | |
Inheritance | De novo | De novo | De novo | De novo | De novo | 5 de novo |
dbSNP | rs786200960 | – | – | – | – | |
GnomAD | – | – | – | 1/250564 | – | |
ClinVar | – | – | – | – | Pathogenic | |
Current age (years) | 16 | 11 | 9 | 8 | 6 | 10 av |
Gender | Male | Male | Female | Male | Female | 2F/3M |
Ethnicity (country of origin) | Caucasian (Spain) | Caucasian (Spain) | Caucasian (Spain) | Caucasian (Spain) | Chinese (China) | |
Neurological | ||||||
Global developmental delay (HP:0001263)/ Intellectual disability (HP:0001249) | + (severe) | + | + | + | + | 5/5 |
Autistic behaviour (HP:0007229) | NE | + | – | + | + | 3/4 |
Speech delay (HP:0000750) | + | + | + | + | + | 5/5 |
Seizures (HP:0001250) | + | + | – | + | – | 3/5 |
Sleep disturbance (HP:0002360) | – | + | – | + | – | 2/5 |
Hypotonia (HP:0001290) | – | – | – | + | + | 2/5 |
Stereotypy (HP:0000733) | + | + | + | – | + | 4/5 |
Lower limb hypertonia (HP:0006895) | + | + | + | – | – | 3/5 |
Unstable gait (HP:0002141) | + | + | + | + | + | 5/5 |
Craniofacial | ||||||
Microcephaly (HP:0000252) | + | + | + | + | + | 5/5 |
Triangular face (HP:0000325) | + | + | + | – | + | 4/5 |
Long face (HP:0000276) | + | – | + | + | + | 4/5 |
Facial asymmetry (HP:0000324) | + | – | – | + (mild) | – | 2/5 |
Frontal bossing (HP:0002007) | + | – | – | + (central) | – | 2/5 |
Midface retrusion (HP:0011800) | – | + | + | – | + | 3/5 |
Sparse medial eyebrows (HP:0025325) | + | + | + | + | + | 5/5 |
Arched eyebrows (HP:0002553) | + | + | + | + | + | 5/5 |
Thin eyebrows (HP:0045074) | + | + | + | – | – | 3/5 |
Swollen skin on the upper eyelids (HP:0012724) | – | – | – | + | – | 1/5 |
Epicanthal folds (HP:0000286) | + (mild) | – | – | + | + | 3/5 |
Proptosis (HP:0000520) | + | – | + (mild) | – | – | 2/5 |
Deep set eyes (HP:0000490) | – | – | + | + | – | 2/5 |
High nasal bridge (HP:0000426) | + | – | – | – | + | 2/5 |
Broad nasal tip (HP:0000455) | + | + | + | – | + | 4/5 |
Bifid nasal tip (HP:0000456) | + | + | + | – | – | 3/5 |
Prominent columella (HP:0009765) | + | – | – | – | – | 1/5 |
Low-set ears (HP:0000369) | + | + | + | – | + | 4/5 |
Anteverted ears (HP:0040080) | – | – | – | + | + | 2/5 |
Prominent antihelix (HP:0000395) | + | + | + | + | + | 5/5 |
Prominent antitragus (HP:0008593) | – | – | + | + (mild) | + | 3/5 |
Hypoplastic tragus (HP:0011272) | – | + | – | + | – | 2/5 |
Small earlobe (HP:0000385) | + | – | + (mild) | + (mild) | – | 3/5 |
Short philtrum (HP:0000322) | – | – | + | + (mild) | – | 2/5 |
Small mouth (HP:0000160) | + | – | – | – | + | 2/5 |
Wide mouth (HP:0000154) | – | – | + | + | – | 2/5 |
Prognathism (HP:0000303) | – | + | + | – | – | 2/5 |
Pointed chin (HP:0000307) | + | + (mild) | + | – | – | 3/5 |
Ocular | ||||||
Convergent strabismus (HP:0000565) | + (left eye) | + | + (left eye) | – | + | 4/5 |
Astigmatism (HP:0000483) | – | + | + | – | – | 2/5 |
Myopia (HP:0000545) | + | + | – | – | – | 2/5 |
Amblyopia (HP:0000646) | + | – | + | – | – | 2/5 |
Nasolacrimal stenosis (HP:0000579) | + | – | + | – | – | 2/5 |
Conjunctivitis (HP:0000509) | – | – | + | – | – | 1/5 |
Thorax & Abdomen | ||||||
Long thorax (HP:0100818) | + | + | + | + | + | 5/5 |
Narrow thorax (HP:0000774) | + | + | + | + | + | 5/5 |
Asymmetric chest (HP:0001555) | pectus excavatum | – | – | – | – | 0/5 |
Wide intermamillary distance (HP:0006610) | + | + | + (mild) | + (mild) | + | 5/5 |
Low-set nipples (HP:0002562) | – | + | NE | + (mild) | + | 3/4 |
Inverted nipple (HP:0003186) | + (left) | – | NE | – | – | 1/4 |
Bulging abdomen (HP:0001538) | – | – | + | – | + | 2/5 |
Prominent umbilicus (HP:0001544) | – | – | + | – | – | 1/5 |
Limbs | ||||||
Skin syndactyly between 3rd and 4th fingers (HP:0011939) | + (mild) | – | – | – | – | 1/5 |
Upper limb amyotrophy (HP:0009129) | + | + | + | + | – | 4/5 |
Lower limb amyotrophy (HP:0007210) | + | + | + | + | – | 4/5 |
Lower limb asymmetry (HP:0100559) | – | – | + | NE | – | 1/4 |
Genu valgum (HP:0002857) | + | – | + (mild) | – | – | 2/5 |
Genu varum (HP:0002970) | – | – | – | + (mild) | – | 1/5 |
Enlargement of the proximal interphalangeal joints (HP:0006185) | + | + (mild) | – | – | – | 2/5 |
Pes planus (HP:0001763) | + | + | + | + | – | 4/5 |
Deviation of the hallux (HP:0010051) | + | – | + | – | – | 2/5 |
Short halluces (HP:0010109) | – | – | + (mild) | + | – | 2/5 |
Sandal gap (HP:0001852) | – | – | – | + | – | 1/5 |
Hammertoe (HP:0001765) | – | – | – | + | – | 1/5 |
Other | ||||||
Prenatal problems (HP:0001197) | IUGR | – | Mild pyelectasis in left kidney; IUGR | – | – | 2/5 |
Cardiovascular problems (HP:0001626) | + | + (atrial septal defect) | + (pulmonary stenosis) | – | + (atrial septal defect) | 4/5 |
Respiratory problems (HP:0002795) | – | + | – | – | – | 1/5 |
Genitourinary problems (HP:0000119) | Small testis and penis; No sphincter control | – | – | Abnomal sphincter control | – | 2/5 |
Feeding problems (HP:0011968) | + | + | + | + | + | 5/5 |
Freckling (HP:0001480) | Freckles on the thorax | Numerous freckles (face and body) | – | – | – | 2/5 |
Webbed neck (HP:0000465) | – | – | – | – | – | 0/5 |