Table 1.

Comparison of clinical features of POLE1 patients and other chromosome instability syndromes

Clinical features	TAR syndrome	Ataxia telangiectasia	RAD50 deficiency	Fanconi anemia	Seckel syndrome	NBS	RS/SC syndrome	Warsaw syndrome	Cernnos-XLF syndrome	Bloom syndrome	LIG4 syndrome2	FILS syndrome*	CMH812
MIM #	274000	208900	613078	227650	210600	251260	268300 /269000	613398	611291	210900	606593	615139	615139
Microcephaly	−	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν
Malar hypoplasia	−	n.a	ν	−	n.a	n.a	ν	ν	−	ν	n.a	ν	ν
Sloping head	ν	−	n.a	−	ν	ν	ν	ν	ν	−	ν	ν	ν
Palpebral fissures, upslanting	−	−	n.a	−	−	ν	−	ν	−	−	ν	ν	−
Palpebral fissures, down-slanting	−	−	ν	−	ν	−	ν	ν	ν	−	−	ν	ν
Epicanthic folds	−	−	ν	−	−	ν	ν	ν	ν	−	ν	ν	ν
Micrognathia	ν	−	n.a	−	ν	ν	ν	ν	ν	−	−	ν	−
External ear abnormalities	−	−	n.a	ν	ν	ν	ν	ν	ν	ν	−	ν	ν
Long/Large nose	ν	−	ν	−	−	ν	ν	ν	ν	ν	ν	ν	−
Long philtrum	−	−	n.a	−	−	ν	ν	ν	ν	−	−	ν	ν
Cleft palate/high arched palate	−	−	n.a	−	ν	ν	ν	ν	−	−	−	−	−
Polydactily	−	−	n.a	ν	−	ν	−	−	−	ν	−	−	−
Clinodactily	−	−	n.a	−	ν	ν	ν	ν	−	ν	ν	−	ν
Syndactily
Growth retardation	−	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν
Short stature	ν	ν	n.a	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν
Bone disease or anomalies	ν	−	n.a	ν	ν	−	ν	n.a	ν	−	−	ν	ν
Thumb apasia/radial ray anormalities	ν	−	n.a	ν	ν	−	−/ν	n.a	−	−	ν		−
Skin abnormalities	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν
Mental retardation	ν	ν	ν	ν	ν	ν	ν	ν	ν	−	ν	−	−
Developemental delay	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	−	ν
Malignancy	ν	ν	−	ν	ν	ν	ν	n.a	ν	ν	ν	−	−
Recurrent infections	−	ν	−	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν
Genital abnormalities	−	−	−	ν	ν	ν	ν	n.a	−	−	ν	−	−
Ataxia	−	ν	ν	−	ν	n.a	−	n.a	−	n.a	n.a	−	−
Brain anomalie/degeneration	CA, CH, aCC, S	CA, CH,T, S	ND	ν	CA, CH, PG, S	ND	S	n.a	PG	n.a	n.a	n.a	−
Endocrine	−	AZ, D, DP, HH	−	HH	D, DP	POF	n.a	n.a	−	AZ, D RF	−	−	−
Immunologic Features
Pancytopenia	−	n.a	n.a	ν	ν	−	n.a	n.a	ν	−	ν	−	ν
Thrombocytopenia	ν	n.a	−	ν	−	−	n.a	n.a	−	−	−	−	ν
CID	−	ν	−	−	n.a	−	n.a	n.a	ν	n.a	ν	2/14	ν
SCID	−	ν	−	−	ν	−	n.a	n.a	ν	n.a	ν	n.a	-
Neutropenia	−	n.a	n.a	ν	n.a	ν	n.a	n.a	ν	N	ν	n.a	-*
B cell lymphocytopenia	−	ν	N	ν	−	−	n.a	n.a	ν	−	2/17	ν	ν
T cell lymphocytopenia	−	ν	N	ν	ν	ν	n.a	n.a	ν	ν	N	ν	ν
IgA	n.a	↓	N	N	↓	n.a	n.a	n.a	↓	↓	↓	N	↑
IgE	n.a	↓	N	n.a	↓	n.a	n.a	n.a	n.a	N	n.a	N	N
IgG	n.a	↓	N	↓	↓	n.a	n.a	n.a	↓	↓	n.a	↓	↓**
IgM	n.a	↓	N	↓	↓	n.a	n.a	n.a	↓	↓	↓	↓	↓
Anti-pseudomonae	n.a	n.a	N	n.a	↓	n.a	n.a	n.a	ν	n.a	n.a	ν	ν
polysaccaride IgG
Auto-immunity	n.a	ν	−	n.a	↓	ν	n.a	n.a	1/17	n.a	0/17	−	-
Sister chromatide	n.a	−	n.a	n.a	↑ or N	ν	ν	ν	n.a	ν	n.a	N	N
DNA breakage studies	n.a	ν	ν	ν	ν	ν	ν	ν	ν	ν	n.a	−	N
Radiosensitivity	n.a	ν	ν	ν	ν	ν	ν	ν	ν	ν	ν	−	n.a.
Gene	RBM8A	ATM	RAD50	FANC	ATR	NBS1	ESCO2	DDX11	NHEJ1	BLM	LIG4	POLE1	POLE1
Mode of Inheritance	AR	AR	AR	AR	AR	AR	AR	AR	AR	AR	AR	AR	AR

Legend

n.a; not reported/applicable.

−; negative.

ν; positive.

N; normal range.

↓; decreased.

↑; increased.

NBS: Nijmegen breakage syndrome.

TAR: Thrombocytopenia-absent radius syndrome.

RS: Roberts syndrome.

SC: SC phocomelia syndrome.

aCC; absence of corpus collosum.

AR; autosomal recessive.

AZ; azoospermia.

CA; cerebellar ataxia.

CH; cerebellar hypoplasia.

CID; combined immunodeficiency.

D; diabetes.

DP; delayed puberty.

HH; hypergonadotropic hypogonadism.

NBS; Nijmegen breakage syndrome.

ND; neurodegenerative.

OA; oculomotor apraxia.

PG; polygyria.

POF; primary ovarian failure.

RF; reduced fertility.

S; seizures.

SCID; severe combined immunodeficiency.

T; Tremor.

*consanguineous family reported.

£ Ataxia-telangiectasia-like disorder.

- * Transient pancytopenia associated with CMV infection.

↓** IgG2 and IgG 4 ↓. Total IgG N.