Introduction
Methods
Results
Clinical features | Pariani et al. [9] | Hamdan et al. [10] | Horn et al. [14] | Carr et al. [15] | Ţuţulan-Cunită et al. [16] | Palumbo et al. [17] | Le Fevre et al. [18] | Lloveras et al. [19] | Dimitrov et al. [20] | Song et al. [21] | Sollis et al., [22]a | Sollis et al. [23] | Siper et al. [24] | Meerschaut et al. [11] | Myers et al. [25]b | Johnson et al. [26]c | Yamamoto et al [27]. | Vuillaume et al. [28] | Urreizti et al. [30] | Mutlu-Albayrak et al. [29] | Total (%) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Number of indviduals | 1 | 2 | 3 | 1 | 1 | 1 | 1 | 1 | 3 | 1 | 2 | 3 | 9 | 25 | 1 | 1 | 3 | 1 | 1 | 1 | 62 |
Age | 1 y 11 m | 9 y 11 m, 15 y 11 m | 7 y, 5 y 6 m, 6 y | 3 y 5 m | 5 y | 20 y | 6 y | 2 y 6 m | 4 y, 4 m, 1 y | 22 y | 7 y, 15 y | 2 y, 3 y 8 m, 7 y 11 m | 5 y - 17 y | 5 m - 23 y | 4 y 5 m | 2 y 11 m | 5 y, 8 y, 5 m | 31 y | 23 y | 4 y | mean = 11.4 y; SD = 7.1 |
Sex | M | 1 M, 1F | 2 M, 1 F | M | M | M | M | F | 1 M, 2 F | F | 1 M, 1 F | 2 M, 1 F | 2 M, 7 F | 20 M, 5 F | F | M | 2 M, 1 F | F | M | M | 41 M:21 F |
Deletion (D) or mutation (Mu) | 1 D | 1 D:1 Mu | 3 D | 1 D | 1 D | 1 D | 1 D | 1 D | 3 D | 1 Mu | 2 Mu | 3 Mu | 9 Mu | 25 Mu | 1 Mu | 1 Mu | 3 D | 1 D | 1 Mu | 1 D | 44 Mu:18 D |
History of hypotonia | - | - | - | 1/1 | - | 1/1 | - | - | - | - | 2/2 | 1/3 | 8/9 | - | 1/1 | 1/1 | 2/3 | 1/1 | - | - | 18/62 (29%) |
Motor delays | 1/1 | 2/2 | 3/3 | 1/1 | 1/1 | 1/1 | 1/1 | 1/1 | 3/3 | 1/1 | 2/2 | 3/3 | 9/9 | 22/24 | 1/1 | 1/1 | 3/3 | 1/1 | 1/1 | 1/1 | 59/61 (97%) |
Gait abnormalities | - | - | - | - | - | - | - | - | - | - | - | - | 7/9 | - | - | 1/1 | - | - | 1/1 | - | 9/62 (15%) |
Speech delays | 1/1 | 2/2 | 3/3 | 1/1 | 1/1 | 1/1 | 1/1 | 1/1 | 3/3 | 1/1 | 2/2 | 3/3 | 9/9 | 23/23 | 1/1 | 1/1 | 2/3 | 1/1 | 1/1 | 1/1 | 60/60 (100%) |
Swallowing or feeding problems | 1/1 | - | 2/3 | - | - | - | 1/1 | - | 3/3 | - | - | - | 3/9 | - | 1/1 | - | 2/3 | - | - | - | 13/62 (21%) |
Articulation problems | - | 2/2 | 3/3 | 1/1 | - | - | 1/1 | - | - | - | 2/2 | 3/3 | 9/9 | 9/11 | - | - | 1/3 | - | 1/1 | - | 32/48 (67%) |
ID or GDD | 1/1 | 2/2 | 3/3 | 1/1 | 1/1 | 1/1 | 1/1 | 1/1 | 2/3 | 1/1 | 2/2 | 3/3 | 8/9 | 23/24 | - | - | 2/2 | 1/1 | 1/1 | 1/1 | 55/61 (90%) |
ASD features | - | 2/2 | - | - | - | 1/1 | - | - | 3/3 | - | 2/2 | - | 4/8 | 14/20 | - | - | - | 1/1 | 1/1 | - | 28/56 (50%) |
Behavioral problems | - | 2/2 | - | - | - | 1/1 | - | - | - | - | 2/2 | 2/2 | 9/9 | 12/19 | - | 1/1 | 2/3 | - | 1/1 | - | 32/56 (57%) |
Dysmorphic features | Pariani et al. [9] | Horn et al. [14] | Carr et al. [15] | Ţuţulan-Cunită et al. [16] | Palumbo et al. [17] | Le Fevre et al. [18] | Lloveras et al. [19] | Blanco Sánchez et al. [31] | Dimitrov et al. [20] | Song et al. [21] | Sollis et al. [22] | Sollis et al. [23] | Siper et al. [24] | Meerschaut et al. [11] | Myers et al. [25] | Johnson et al. [26] | Yamamoto et al. [27] | Vuillaume et al. [28] | Urreizti et al. [30] | Mutlu-Albayrak et al. [29] | Total (%) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Head and facial features | |||||||||||||||||||||
Macrocephaly | - | - | - | - | - | 1/1 | - | - | - | - | - | 1/3 | 4/8 | - | - | 1/1 | - | - | 1/1 | 1/1 | 9/59 (15%) |
Frontal hair upsweep | - | 2/3 | - | - | - | - | - | - | - | 1/1 | - | - | 2/8 | 10/24 | 1/1 | - | - | - | - | - | 16/59 (27%) |
Prominent forehead | - | 2/3 | 1/1 | 1/1 | 1/1 | 1/1 | - | 1/1 | 2/3 | 1/1 | 1/2 | 2/3 | 6/8 | 23/24 | - | 1/1 | 3/3 | - | 1/1 | 1/1 | 48/59 (81%) |
Flat midface | - | - | - | - | - | 1/1 | - | - | 1/3 | - | - | - | - | - | - | - | - | - | 1/1 | - | 3/59 (5%) |
Long philtrum | - | - | - | - | - | - | - | - | - | - | - | - | 3/8 | - | - | - | - | - | - | - | 3/59 (5%) |
Short philtrum | - | - | - | 1/1 | - | - | - | - | 1/3 | - | - | - | - | - | - | - | 2/3 | - | - | - | 4/59 (7%) |
Pointed chin | - | - | - | 1/1 | - | - | - | - | - | - | - | 1/8 | 9/22 | - | 1/1 | - | - | - | - | 12/57 (21%) | |
Eyes | |||||||||||||||||||||
Epicanthal folds | 1/1 | - | - | 1/1 | - | - | - | - | - | - | - | - | 3/8 | - | - | - | - | - | - | - | 5/59 (8%) |
Down slanted palpebral fissures | - | 1/3 | 1/1 | - | 1/1 | 1/1 | - | 1/1 | 1/3 | - | 1/2 | 1/3 | - | 14/24 | - | - | - | - | 1/1 | 1/1 | 24/59 (41%) |
Short palpebral fissures | 1/1 | - | - | 1/1 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | 2/59 (3%) |
Ptosis | 1/1 | - | 1/1 | - | 1/1 | - | - | - | - | - | - | - | 1/8 | 16/24 | - | - | - | - | 1/1 | 1/1 | 22/59 (37%) |
Hypertelorism | - | - | 1/1 | - | 1/1 | - | - | - | 3/3 | - | 2/2 | 1/3 | 4/8 | - | - | - | 3/3 | - | 1/1 | 1/1 | 17/59 (29%) |
Blepharophimosis | 1/1 | - | - | - | - | - | - | - | - | - | - | - | - | 4/24 | - | - | - | - | - | - | 5/59 (8%) |
Coloboma | - | - | - | - | - | - | - | - | 2/3 | - | - | - | - | - | - | - | - | - | - | - | 2/59 (3%) |
Ears | |||||||||||||||||||||
Malformed ears | - | - | - | 1/1 | - | - | - | - | 2/3 | - | - | 1/3 | - | - | 1/1 | 1/1 | 2/3 | - | 1/1 | 1/1 | 10/59 (17%) |
Nose | |||||||||||||||||||||
Short nose with broad tip | 1/1 | 1/3 | 1/1 | - | 1/1 | 1/1 | - | 1/1 | 2/3 | 1/1 | 2/2 | 2/3 | 5/8 | 19/24 | - | - | 2/3 | - | 1/1 | 1/1 | 41/59 (69%) |
Broad nasal bridge | - | - | - | 1/1 | - | - | - | - | 1/3 | - | - | - | 6/8 | - | - | - | - | - | - | - | 8/59 (14%) |
Mouth | |||||||||||||||||||||
Thick vermillion | - | - | - | - | 1/1 | - | - | - | - | - | - | - | 3/8 | 14/24 | - | - | - | - | - | - | 18/59 (31%) |
High-arched palate | - | - | - | - | - | - | - | 1/1 | 1/3 | - | - | - | 4/8 | - | - | - | 2/3 | 1/1 | 1/1 | - | 10/59 (17%) |
Malocclusion | - | - | - | - | 1/1 | - | - | - | - | - | - | - | 3/8 | - | - | - | - | - | - | - | 4/59 (7%) |
Extremities | |||||||||||||||||||||
Hyperflexibility of joints | - | - | - | - | - | - | - | - | - | 1/1 | - | - | 1/8 | - | - | - | - | - | - | 1/1 | 3/59 (5%) |
Clinodactyly | 1/1 | - | - | - | - | 1/1 | - | - | - | - | - | - | 4/8 | 6/21 | - | - | - | - | 1/1 | - | 13/56 (23%) |
Single palmar crease | 1/1 | - | - | - | - | - | - | - | 3/3 | - | - | - | 2/8 | 8/21 | - | - | - | - | - | - | 14/56 (25%) |
Prominent finger pads | - | - | 1/1 | - | - | 1/1 | - | - | - | - | - | 1/3 | - | 2/22 | 1/1 | - | - | - | - | - | 6/57 (11%) |
Partial syndactyly 2nd and 3rd toes | - | - | - | - | - | - | 1/1 | - | - | - | - | - | 1/8 | - | - | - | - | - | - | 1/1 | 3/59 (5%) |
Sandal gap | - | - | - | - | - | - | - | - | 2/3 | - | - | - | - | - | - | - | - | - | - | - | 2/59 (3%) |
Other | |||||||||||||||||||||
Sacral dimple | - | - | - | - | - | - | - | - | 2/3 | - | 1/2 | - | 1/8 | - | - | - | - | - | - | - | 4/59 (7%) |
Medical Features | Pariani et al. [9] | Hamdan et al. [10] | Horn et al. [14] | Carr et al. [15] | Ţuţulan-Cunită et al. [16] | Palumbo et al. [17] | Fevre et al. [18] | Lloveras et al. [19] | Dimitrov et al. [20] | Song et al. [21] | Sollis et al. [22] | Sollis et al. [23] | Siper et al. [24] | Meerschaut et al. [11] | Myers et al. [25] | Johnson et al. [26] | Yamamoto et al [27]. | Vuillaume et al. [28] | Urreizti et al. [30] | Mutlu-Albayrak et al. [29] | Total (%) |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Neurology | |||||||||||||||||||||
Spinal defects | - | - | - | - | 1/1 | - | - | - | - | - | - | - | 1/9 | 2/23 | - | - | - | - | - | - | 2/60 (3%) |
Hypertonia/muscle spasms | 1/1 | - | - | 1/1 | - | - | - | - | 3/3 | - | - | - | - | 14/21 | - | - | - | - | 1/1 | - | 20/58 (34%) |
Abnormal reflexes | - | - | - | 1/1 | 1/1 | - | - | - | 3/3 | - | - | - | - | - | - | - | - | - | - | - | 5/60 (8%) |
Spastic/contractures | 1/1 | - | - | - | 1/1 | - | - | - | 3/3 | - | - | - | - | 10/19 | - | - | - | - | 1/1 | - | 16/56 (29%) |
Seizures | - | - | - | 1/1 | - | - | - | - | 1/3 | - | - | 1/3 | 0/9 | 3/22 | - | - | - | 1/1 | - | - | 7/59 (12%) |
Brain abnormalities | 1/1 (a) | - | - | 1/1 (b) | 1/1 (c) | - | 1/1 (d) | - | 3/3 (e) | - | - | 1/2 (f) | 6/7 (g) | 11/23 (h) | - | 1/1 (i) | 1/3 (j) | 1/1 (k) | - | 1/1 (l) | 29/58 (50%) |
Abnormal EEG | - | - | - | 1/1 | - | 1/1 | - | - | - | - | - | - | 2/4 | - | - | - | - | - | - | - | 4/55 (7%) |
Endocrinology | |||||||||||||||||||||
Short stature | 1/1 | - | - | - | - | - | - | - | 3/3 | 1/2 | - | - | - | - | - | - | 3/3 | - | - | - | 8/60 (13%) |
Obesity | - | - | 2/3 | - | - | - | - | - | - | - | - | - | 1/9 | - | - | - | - | - | - | - | 3/60 (5%) |
Hypothyroidism | - | - | - | - | - | - | - | - | - | - | - | - | 1/9 | - | - | - | - | - | - | 1/3 | 2/60 (3%) |
Diabetes | - | - | - | - | - | - | - | - | - | - | - | - | 1/9 | - | - | - | - | - | - | - | 1/60 (2%) |
Cardiac | |||||||||||||||||||||
Congenital heart defect | - | - | - | - | 1/1 (i) | - | - | 1/1 (ii) | 3/3 (iii) | - | - | - | 2/9 (iv) | 9/19 (v) | - | - | 1/3 (vi) | - | - | - | 17/56 (30%) |
Nephrology/urology | |||||||||||||||||||||
Renal abnormalities | - | - | - | - | - | - | - | - | - | - | - | - | - | 1/9 (HK) | - | 1/1 (HK) | - | - | 1/1 (HK) | - | 3/46 (7%) |
Micropenis | - | - | - | - | 1/1 | - | - | - | 1/3 | - | - | 1/3 | - | - | - | - | - | - | - | - | 3/41 (7%) |
Cryptorchidism | 1/1 | - | - | - | 1/1 | - | - | - | 1/3 | - | - | 2/3 | - | - | - | 1/1 | 1/3 | - | 1/3 | 1/3 | 9/41 (22%) |
Ophthalmology | |||||||||||||||||||||
Visual refractive error | 1/1 | - | 1/3 | - | - | - | - | - | - | - | 1/2 | 3/3 | 5/9 | 17/21 | - | - | - | - | 1/1 | - | 29/58 (50%) |
Strabismus | - | - | - | - | 1/1 | - | - | - | - | - | 1/2 | 3/3 | 5/9 | - | - | - | - | - | - | 1/1 | 11/60 (18%) |
Other eye abnormalities | - | - | - | - | - | - | - | - | 1/3 | - | - | 1/3 | - | - | - | - | 1/3 | - | - | - | 3/60 (5%) |
Other medical problems | |||||||||||||||||||||
Recurrent infections (ear) | - | - | - | - | - | - | - | - | - | - | - | 1/3 | 6/9 | - | - | - | - | - | - | - | 7/60 (12%) |
Hypoacusis, hearing loss | - | - | - | - | 1/1 | - | - | - | 1/3 | - | - | - | 1/9 | 2/11 | - | - | 3/3 | - | - | - | 8/48 (17%) |
Recurrent upper respiratory tract infections | - | - | - | - | - | - | - | - | 2/3 | - | - | - | 4/9 | - | 1/1 | - | - | - | - | - | 7/60 (12%) |
Neuroendocrine hyperplasia of infancy | - | - | - | - | - | - | - | - | - | - | - | - | 1/9 | - | - | - | - | - | - | - | 1/60 (2%) |
Pulmonary hypertension | - | - | - | - | - | - | - | - | 2/3 | - | - | - | 1/9 | - | - | - | 1/3 | - | - | - | 4/60 (7%) |
Obstructive sleep apnea | 1/1 | - | - | - | - | - | - | - | 1/3 | - | - | - | - | - | - | - | - | - | - | - | 2/60 (3%) |
Asthma | - | - | - | - | - | - | 1/1 | - | - | - | - | - | - | - | - | - | - | - | - | - | 1/60 (2%) |
Gut atresia | - | 1/2 | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | 1/60 (2%) |
Constipation | - | - | - | - | - | - | - | - | - | - | - | - | 4/9 | - | 1/1 | - | - | - | - | - | 5/60 (8%) |
Skin infections | - | - | - | - | - | - | - | - | - | - | - | - | 2/9 | - | - | - | - | - | - | - | 2/60 (3%) |
Allergies | - | - | - | - | - | - | - | - | - | - | - | - | 2/9 | - | - | - | - | - | - | - | 2/60 (3%) |
Iron deficiency | - | - | - | - | - | - | - | - | - | - | - | - | 2/9 | - | - | - | - | - | - | - | 2/60 (3%) |
Sleep issues | - | - | - | - | - | - | - | - | - | - | - | 1/3 | - | - | - | - | 1/3 | 1/1 | - | - | 3/60 (5%) |
Congenital hip dislocation | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | - | 1/3 | - | - | 1/1 | 2/60 (3%) |
Clinical genetics
Recommendations
Psychology and psychiatry
Recommendations
Neurology
Recommendations
Seizure assessment
Recommendations
Brain imaging
Recommendations
Endocrinology
Recommendations
Cardiology
Recommendations
Nephrology
Recommendations
Ophthalmology and hearing
Recommendations
Other medical problems
Recommendations
Discussion
Conclusions
Medical specialty | Clinical features | Assessments |
---|---|---|
Clinical genetics | Autism spectrum disorder (ASD), intellectual disability (ID), or developmental delay | For affected individuals, chromosomal microarray to identify 3p14 microdeletions; whole exome, whole genome sequencing, or next-generation sequencing panels for ASD and ID For parents, chromosome analysis and fluorescence in situ hybridization to identify rearrangements |
Prominent forehead | Dysmorphology exam and specialty referrals | |
Frontal hair upsweep | ||
Down slanting palpebral fissures | ||
Ptosis | ||
Single palmar crease | ||
Clinodactyly | ||
Psychiatry and psychology | Autism spectrum disorder | Gold-standard diagnostic testing |
Intellectual disability | Cognitive and adaptive behavior testing | |
Delayed speech, articulation problems | Speech and language evaluation and therapy | |
Maladaptive behaviors | Psychiatric evaluation, medication management | |
Neurology | Seizures | Electroencephalography |
Structural brain abnormalities | Brain imaging and head circumference monitoring | |
Feeding difficulties | Feeding therapy evaluation | |
Hypotonia | Occupational and physical therapy evaluations | |
Motor skill deficits | Physical therapy | |
Endocrinology | Short stature and obesity | Monitor height, weight, body mass index, and pubertal development |
Cardiology | Mild congenital heart defects | Referral to cardiology for echocardiography and electrocardiography |
Nephrology | Mild genitourinary malformations | If urinary tract infection or voiding dysfunction, renal ultrasound |
Otolaryngology | Recurring ear infections and hearing problems | Hearing test and consider ear tube placement |
Ophthalmology | Vision problems | Eye exam |
Primary care/pediatrics | Upper respiratory tract infections, gastroesophageal reflux, and constipation | Careful and consistent monitoring and management |
Dentistry | High arched palate and malocclusion | Routine dental exams |