Table 3. [Selected Chromatin-Modifying Disorders of Interest...]. - GeneReviews®

Gene	Disorder	MOI	Clinical Characteristics
ASXL3	Bainbridge-Ropers syndrome	AD	DD/ID w/speech & language delay &/or absent speech. Autistic features & issues w/feeding in some persons. Typically nonspecific dysmorphic facial features. Affected persons may have hypotonia that can transition to spasticity resulting in unusual posture w/flexion contractions of elbows, wrists, & fingers.
DNMT3A ¹	Tatton-Brown-Rahman syndrome	AD	Overgrowth/ID syndrome. Obesity / ↑ weight, joint hypermobility, hypotonia, behavioral/psychiatric issues, kyphoscoliosis, & seizures. Subtle dysmorphic features, incl round face w/coarse features, thick horizontal low-set eyebrows, narrow (as measured vertically) palpebral fissures, & prominent upper central incisors. (Facial gestalt is most easily recognizable in teenage yrs.)
Heyn-Sproule-Jackson syndrome (OMIM 618724)	AD	DD/ID; microcephaly; short stature; strabismus
FMR1	Fragile X syndrome (See FMR1 Disorders.)	XL	Characterized in males by DD & ID w/variety of behavioral issues. ASD in 50%-70%. Characteristic craniofacial features, hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, & recurrent otitis media.
KMT2D KDM6A	Kabuki syndrome	AD XL	Typical facial features (long palpebral fissures w/eversion of lateral 3rd of lower eyelid; arched, notched, & broad eyebrows; short columella w/depressed nasal tip; large, prominent, or cupped ears), minor skeletal anomalies, infantile hypotonia, persistence of fetal fingertip pads, ID, & postnatal growth deficiency.
NFIX	Malan syndrome (OMIM 614753)	AD	DD/ID; macrocephaly; tall stature; tall/broad forehead; long face; strabismus; nystagmus; hypotonia; anxiety
NSD1	Sotos syndrome	AD	Cardinal features (present in ≥90% of persons w/Sotos syndrome) are distinctive facial appearance (broad & prominent forehead w/dolichocephalic head shape; sparse frontotemporal hair; downslanting palpebral fissures; malar hypoplasia & flushing; long & narrow face; long chin), learning disability, & overgrowth.
SETD2	SETD2 neurodevelopmental disorder ± macrocephaly/ overgrowth (Luscan-Lumish syndrome) (See SETD2 Neurodevelopmental Disorders.)	AD	Macrocephaly/overgrowth. Can also include DD/ID, obesity, advanced bone age, & behavioral findings (most typically ASD). This spectrum also includes individuals who have normal growth.

Gene

Disorder

MOI

Clinical Characteristics

ASXL3

DD/ID w/speech & language delay &/or absent speech. Autistic features & issues w/feeding in some persons. Typically nonspecific dysmorphic facial features. Affected persons may have hypotonia that can transition to spasticity resulting in unusual posture w/flexion contractions of elbows, wrists, & fingers.

DNMT3A ¹

Tatton-Brown-Rahman syndrome

Overgrowth/ID syndrome. Obesity / ↑ weight, joint hypermobility, hypotonia, behavioral/psychiatric issues, kyphoscoliosis, & seizures. Subtle dysmorphic features, incl round face w/coarse features, thick horizontal low-set eyebrows, narrow (as measured vertically) palpebral fissures, & prominent upper central incisors. (Facial gestalt is most easily recognizable in teenage yrs.)

Heyn-Sproule-Jackson syndrome (OMIM 618724)

DD/ID; microcephaly; short stature; strabismus

FMR1

Fragile X syndrome (See FMR1 Disorders.)

Characterized in males by DD & ID w/variety of behavioral issues. ASD in 50%-70%. Characteristic craniofacial features, hypotonia, gastroesophageal reflux, strabismus, seizures, sleep disorders, joint laxity, pes planus, scoliosis, & recurrent otitis media.

KMT2D
KDM6A

Kabuki syndrome

AD
XL

Typical facial features (long palpebral fissures w/eversion of lateral 3rd of lower eyelid; arched, notched, & broad eyebrows; short columella w/depressed nasal tip; large, prominent, or cupped ears), minor skeletal anomalies, infantile hypotonia, persistence of fetal fingertip pads, ID, & postnatal growth deficiency.

NFIX

Malan syndrome (OMIM 614753)

DD/ID; macrocephaly; tall stature; tall/broad forehead; long face; strabismus; nystagmus; hypotonia; anxiety

NSD1

Sotos syndrome

Cardinal features (present in ≥90% of persons w/Sotos syndrome) are distinctive facial appearance (broad & prominent forehead w/dolichocephalic head shape; sparse frontotemporal hair; downslanting palpebral fissures; malar hypoplasia & flushing; long & narrow face; long chin), learning disability, & overgrowth.

SETD2

SETD2 neurodevelopmental disorder ± macrocephaly/
overgrowth (Luscan-Lumish syndrome) (See SETD2 Neurodevelopmental Disorders.)

Macrocephaly/overgrowth. Can also include DD/ID, obesity, advanced bone age, & behavioral findings (most typically ASD). This spectrum also includes individuals who have normal growth.

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