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Table 1 Phenotypic data in individuals with TCF20 mutations

From: De novo and inherited TCF20 pathogenic variants are associated with intellectual disability, dysmorphic features, hypotonia, and neurological impairments with similarities to Smith–Magenis syndrome

Subject Age/sex ID Neurobehavioral abnormalities Dysmorphic facial features Sleep disturbance Macrocephaly Overgrowth Digital anomalies Seizures Motor delay Hypotonia Movement disorder Language delay Structural brain abnormalities Other features, additional variants detected
#1 3 y
+ NR Coarse facies, wide nasal bridge, long eyelashes, tented upper lip NR NR Nocturnal epilepsy + NR NR + NR Duplicated left kidney, atrial septal defect, tethered spinal cord, dilated coronary artery
14.3 y
+ NR Frontal bossing, full cheeks NR + Long fingers with contracture of 5th finger, long toes NR + NR NR + NR Joint hypermobility, increased carrying angle
#3 20 y
NR ASD, ADHD, anxiety NR NR Borderline + NR NR + Congenital Dyspraxia + NR NR
#4 3.25 y
NR ASD Frontal bossing, triangular face + + NR NR NR + NR Visuo spatial perception difficulty, dyspraxia NR NR NR
# 5
8.5 y
Moderate NR Mild dysmorphic facial features with depressed nasal bridge NR NR NR Severe + NR Severe NR Feeding difficulties (tube fed)
#6 10.2 y
+ ASD NR NR NR NR Complex partial intractable + Congenital Ataxia Severe expressive/mild receptive Mild cerebellar atrophy Growth retardation, short stature, type 2 fiber muscular atrophy, laryngeal cleft, recurrent otitis media
#7b 10 y
+ ASD, ADHD, anxiety, self-harming behavior Mild Tapered 5th fingers with minor cutaneous 2–3 to syndactyly Epileptic disorder with multifocal origin + Congenital generalized NR + NR De novo
c.1189C>T, p.Gln397* in SLC6A1
6.9 y
+ ADHD Abnormal hair whorl + NR NR + + NR NR + NR NR
11.9 y
+ ADHD, obsessive–compulsive trait Brachycephaly, low-set ears NR Finger-tip pads, sandal gap, clinodactyly of the 5th toe NR NR Abnormal movement NR Inverted nipples, feeding difficulties, microcephaly
11.5 y
Moderate Obsessive compulsive, food-seeking, aggression Abnormal facial shape + + Overweight NR NR Moderate + NR Severe receptive and expressive NR NR
#11 3.9 y
+ ASD Deep-set eyes, hypertelorism, long philtrum, tented upper lips, wide mouth, full lips, mild coarsening + + NR NR + Congenital generalized Distal spasticity Severe expressive/receptive NR
3 y
NR ASD USPFs, epicanthus, short nose, depressed nasal bridge, short lingual frenulum + NR NR + NR NR + NR NR
#13 1.2 y
+ NR Plagiocephaly, epicantal folds, depressed nasal roots, tented upper lip + NR NR 5th finger clinodactyly NR + NR NR + NR NR
# 14
7.9 y
Mild Hyperactivity USPFs, anteverted nares NR 5th finger clinodactyly Febrile seizures Mild Mild Motor coordination disorder Mild NR Oligohydramnios on 20 weeks scan, ptosis, drooling, fatigue
# 15
2.5 y
NR NR Brachycephaly, myopathic facies, depressed nasal bridge, anteverted nares, open mouth with downturned angles NR NR NR + + Gait ataxia + NR NR
6.5 y
Mild ASD, ADHD NR NR NR NR Moderate + Moderate + NR
#17b 5.4 y
+ ASD, self-injurious, aggression, hyperactivity, food-seeking behavior Midface hypoplasia, bulbous nose, tented upper lips + NR NR + Congenital generalized NR Severe expressive/receptive NR De novo
c.1307G>T (p.R436L) in ZBTB18
9 y
+ Hyperactivity High anterior hairline, large and tall forehead, temporal hypotrichosis, low-set, posteriorly rotated ears, broad philtrum, narrow mouth NR Broad hallux, 2–3 toe syndactyly NR + + NR + NR Strabismus, joint hypermobility, drooling
10.2 y
NR ASD, hyperactivity Brachycephaly NR Tall stature Contracture of 5th finger + + NR Paroxysmal dyskinesia + NR High-pitched voice, ichthyosis (due STS deficiency)
#20 8.1 y
+ NR + NR NR NR NR Mild Congenital generalized Impaired coordination, increased tone at the elbows Expressive NR NR
33.3 y M Moderate NR NR NR Tall stature NR NR NR NR NR NR NR High-pitched voice
9.9 y
Severe NR Deep-set eyes, full cheeks, long face, tall forehead, prominent lower lip and chin, sunken eyes NR + + Slender fingers NR + + Jerky movements + NR Hypermetropia, amblyopia
4 y
NR ASD Broad forehead, short nose, depressed nasal bridge NR NR NR + NR NR + + Inverted nipples
7.8 y
NR ASD Low-set ears NR NR + + NR NR + NR NR
#25 5.3 y
+ ASD Mild + NR NR Mild Congenital generalized NR Severe expressive NR Hypohidrosis
#26 a
3.1 y
NR ASD Long eyelashes, DSPFs, epicanthic folds, everted lower lip, open mouth NR Tapered fingers NR + + NR NR Delayed CNS myelination and lack of cerebral white matter NR
17 y
Moderate Plagiocephaly, bilateral ptosis, horizontal crus of helix, malar flattening, narrow mouth NR Truncal obesity Short, tapering fingers with incurved 5th fingers, mild bilateral hallux valgus Mild + Motor coordination difficulties + Right posterior plagiocephaly Inverted nipples
17 y
Moderate Plagiocephaly, bilateral ptosis, horizontal crus of helix, malar flattening, narrow mouth NR Truncal obesity Short, tapering fingers with incurved 5th fingers, mild bilateral hallux valgus Mild + Motor coordination difficulties + Right posterior plagiocephaly Inverted nipples, High arched palate
#29 4 y
+ Repetitive behavior, ASD,ADHD NR + NR NR Mild Congenital generalized NR Mixed severe expressive/receptive NR NR
#30 14 y
+ active autistic disorder + + + NR NR NR Mild Congenital generalized NR + NR Scoliosis
#31 5 y
+ NR NR NR + + NR + + Congenital generalized Balance disorder + NR NR
#32 1.1 y
+ Autistic features, food-seeking behavior Midface hypoplasia, long eyelashes, thick lips, occipital groove + + NR NR NR + Mild generalized Mild spasticity in ankle dorsiflexors Significant expressive/receptive Cavum septum pellucidum and vergae Dysphagia, GERD, renal cyst, delayed visual maturation
Schafgen et al. [14];
Babbs et al. [6];
Lelieveld et al. [15];
McRae et al. [16]*
n = 2 (12–14 y, M);
n = 4 (n = 3F, 1 M);
n = 6 (NR)
Mild to moderate (n = 8/12) Autistic features (n = 5/12), stereotypic behavior (n = 1/12), aggression (n = 1/12) n = 4/12 NR n = 3/12 n = 2/12 n = 1/12 n = 1/12 n = 5/12 n = 3/12 NR n = 5/12 Abnormality of the cerebrum n = 2/12 Inverted nipples (n = 2/12), tapered fingers (n = 1/12), small penis (n = 1/12), abnormal eye physiology (n = 1/12), abnormality of the mouth (n = 1/12)
  1. Abbreviations: ID intellectual disability, M male, F female, y year old, NR not reported, N/A not applicable, + present feature, − absent feature, ASD autism spectrum disorder, ADHD attention-deficit hyperactivity disorder, FTT failure to thrive, USPF upslanting palpebral fissures, DSPF downslanting palpebral fissures, IUGR, intrauterine growth retardation, GERD gastro-esophageal reflux disorder
  2. aFive patients from the original McRae et al. DDD cohort [16] (individual #2, #8, #10, #19, and #26) were included in this study
  3. bThe clinical phenotype in subjects #7 and #17 might result from a combination of TCF20 variants and additional contributions in variants detected in SLC6A1 and ZBTB18, respectively
  4. *Two additional patients from this study were included in the meta-analysis from previous studies