Table 2.

Other Disorders to Consider in the Differential Diagnosis of ARID1B Coffin-Siris Syndrome (CSS)

Differential Diagnosis DisorderGene(s) /
Genetic Mechanism		MOIClinical Features of Differential Diagnosis Disorder
Overlapping w/ARID1B-CSSDistinguishing from ARID1B-CSS
Coffin-Siris syndrome caused by genes other than ARID1B ARID1A
DPF2
SMARCC2
SMARCA4
SMARCB1
SMARCE1
SOX11 		ADFrequently clinically indistinguishable from ARID1B-CSSMicrocephaly seen more frequently in individuals w/a heterozygous pathogenic variant in SMARCB1 or SMARCE1
Nicolaides-Baraitser syndrome SMARCA2 AD
  • Characteristic coarse facial features
  • Sparse scalp hair
  • ID
  • Prominence of interphalangeal joints & distal phalanges due to ↓ subcutaneous fat
  • Absence of 5th-digit nail / distal phalanx hypo/aplasia
Borjeson-Forssman-Lehmann syndrome
(OMIM 301900)		 PHF6 XLAffected females demonstrate some phenotypic overlap w/CSS, incl hypoplastic nails & fingers, sparse hair, & intellectual disability. 1, 2
  • Other digital anomalies incl tapering of digits, hammer toes, syndactyly of toes
  • Distinct facial gestalt incl prominent supraorbital ridges, deeply set eyes, prominent nasal bridge, short nose w/bulbous nasal tip
ARID2-ID
(OMIM 617808)		 ARID2 AD
  • Hypotonia
  • Behavior anomalies
  • Very mild hypoplasia of 5th fingernails & hypoplasia of 5th toenails in some individuals
  • Facies: coarse features, flat nasal bridge, slightly broad nose, prominent philtrum, & large mouth w/thick lower vermilion 3
  • ID
Birth defects not common
DOORS (deafness, onychodystrophy, osteodystrophy, mental retardation, & seizures) syndrome
(See TBC1D24-Related Disorders.)		 TBC1D24 AR
  • Hypoplastic terminal phalanges &/or nail anomalies
  • Deafness
  • Neurologic abnormalities
  • ID
  • Osteodystrophy
  • Profound hearing loss (can occasionally occur in ARID1B-CSS)
Mabry syndrome
(OMIM 239300)		 PIGV AR
  • Delayed development & ID
  • Seizures
  • Coarse facial features
  • Hypoplastic 5th digits
↑ serum concentrations of alkaline phosphatase
Cornelia de Lange syndrome HDAC8
NIPBL
RAD21
SMC1A
SMC3 		AD,
XL
  • Limb anomalies may incl 5th-finger hypoplasia.
  • ID
  • Other findings may incl cardiac defects, gastrointestinal anomalies, & genitourinary malformations.
Distinctive craniofacial features (arched eyebrows, synophrys, upturned nose, small teeth, & microcephaly)
4q21 deletion syndrome
(OMIM 613509)		Contiguous-gene deletionAD 1
  • Curved, volar, 5th-digit nail that may resemble a hypoplastic distal phalanx
  • ID
  • Facial gestalt may incl broad forehead, widely spaced eyes, & frontal bossing.
  • Postnatal growth restriction may be severe.

AD = autosomal dominant; AR = autosomal recessive; CSS = Coffin-Siris syndrome; ID = intellectual disability; MOI = mode of inheritance; XL = X-linked

1.

To date, all reported probands have had the disorder as the result of a de novo deletion.

2.
3.

While some of these features demonstrate overlap with CSS, an assessment of a larger cohort of individuals with ARID2 pathogenic variants will be needed to determine whether it is clinically similar to or distinct from CSS.

From: ARID1B-Related Disorder

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