Table 2. Comparison of BDCS and FTHS clinical features.

	Borrone Dermato-Cardio-Skeletal Syndrome					Frank-ter haar Syndrome
Family	BDCS 1	BDCS 31	BDCS 3	BDCS 22	BDCS 2	FTHS 22	FTHS 2	FTHS 612, 16	FTHS 712, 17	FTHS 7
Patient	1–17	3–3	3–4	2–2	2–3	1	2	1	1	2
Gender	M	M	M	M	M	M	M	F	M	F
Max. age of symptom report	8 years	36 years	23 years	19 years	17 years	5.5 years	1 yr	6.4 years	13 months	34 days
Age at death (years)	8	−	24	−	−	−	1	−	−	−
Mutation detected
SH3PXD2B	c.401+1G>A	c.1188+1773_2733+6592del	c.1188+1773_2733+6592del	−	−	c.147insT	c.147insT	c.969delG	Deletiona	Deletiona
Protein alteration	p.(Glu134Glufs*1)	LP	LP	−	−	p.(F49*)	p.(F49*)	p.(G323fs*19)	LP	LP
Developmental anomalies
Motor retardation	−	−	−	−	−	+	+	+	+	+
Craniofacial abnormalities
Acne	−	+	+	+	+	NR	NR	NR	NR	NR
Coarse face and thick skin	+	+	+	+	+	NR	NR	+	NR	NR
Gingival enlargement	+	+	+	−	−	+	NR	NR	+	+
Prominent forehead	+	+	+	+	+	+	+	+	+	+
Brachycephaly	+	+	NR	NR	NR	+	+	+	+	+
Wide anterior fontanel	NR	NR	NR	NR	NR	+	+	+	+	+
Hypertelorism	+	+	+	+	+	+	NR	+	+	+
Congenital glaucoma	−	NR	NR	NR	NR	+	NR	−	+	+
Large cornea	−	NR	NR	NR	NR	+	NR	+	+	+
Prominent eyes	+	NR	NR	−	−	+	+	+	+	+
Full cheeks	+	+	+	+	+	+	+	+	+	+
Anteverted nostrils	−	+	+	−	−	NR	+	−	+	+
Broad mouth	+	+	+	+	+	+	+	+	+	+
Broad alveolar ridges	+	NR	NR	NR	NR	NR	NR	+	+	+
Micrognathia	+	+	+	−	−	+	+	−	+	+
Protruding ears	−	+	NR	−	−	+	+	+	−	−
Cardiac deficiencies
Mitral valve anomaly	+	+	+	+	+	+	NR	+	NR	NR
Double right outlet	−	−	−	−	−	NR	+	−	NR	NR
Ventricular septal defect	−	−	−	−	−	NR	NR	+	−	+
Skeletal abnormalities
Vertebral anomalies	+	+	+	+	−	+	−	−	NR	NR
Prominent coccyx	−	−	−	−	−	+	+	+	+	+
Bowing of long bones	+	+	−	−	−	+	+	−	+	+
Short hands	+	+	+	+	+	+	+	+	+	+
Flexion deformity	+	+	+	+	+	−	−	+	+	+
Club feet	+	−	−	−	−	+	−	PA	+	+
Bone abnormalities
	Osteopenia	Cortical erosions	Cortical erosions	Cortical erosions	NR	Cortical anomalies	Cortical anomalies	Osteopenia	Osseous defects	Osseous defects
		Osteoporosis	Osteoporosis
		Osteolytic lesions
		Arthropathy
Additional clinical features
	Genu valgum	Irregular tongue		Gynecomastia	Umbilical hernia	Muscle weakness Irregular contoured ribs	Hypotonia	Gall stones	Pectus excavatum	Pectus excavatum
	Radial head dislocation	Inguinal hernia		Thickening of interphalangeal joints	Thickening of interphalangeal joints			Joint hypermobility	Small pituitary
	Thoracic wall deformity	Genu recurvatum						Inguinal hernia	Wormian bones
	Thickened interphalangeal joints							Loose skin
								Digital fetal pads
								Hirsutism

Abbreviations: LP, loss of protein; M, male; NR, not reported; PA, pes adductus.

The reported clinical features of BDCS and FTHS cases affected by an SH3PXD2B mutation were tabulated for comparison; only cases with a published report describing the patient phenotype were included. The table highlights the phenotypic variability reported in BDCS/FTHS despite the common occurrence of truncating loss of protein mutations. This variability may be partially accounted for by the documentation of follow-up consultations to monitor the disease progression, indicated by the maximum (Max.) age of symptom reports and also the patients age at death.

^aThe deletion occurring in FTHS family 7 incorporated SH3PXD2B and UBTD2. The deletion of the two genes did not obviously alter the phenotype in comparison with patients carrying only a SH3PXD2B truncating mutation.¹⁷