Case Reports in Genetics

Case Report

Mechanism of Disease: Recessive ADAMTSL4 Mutations and Craniosynostosis with Ectopia Lentis

Table 1

Patients with craniosynostosis and ectopia lentis reported to date.


Publication	Sex	Age CS	Age EL	Race/ethnicity	CS phenotype	EL phenotype	Gene affected	Nucleotide variant (s)	Protein variant (s)	Gnomad MAF
Patients described in this paper
Patient 1	M	1 mo	4 mo	Caucasian	Bilateral coronal	Bilateral EL	ADAMTSL4	c.767_786del, c.2177 + 3_2177 + 6delGAGT	p.Gln256Profs38, (intronic - splice acceptor deletion)	0.001219, 0.000009137
Patient 2⁺	M	5 mo	Birth	Swedish	Sagittal	Bilateral EL/P	ADAMTSL4	c.767_786del, c.767_786del	p.Gln256Profs38, p.Gln256Profs38	0.001219

Previously published ADAMTSL4-associated CS/EL patients
[28]	M	ND	ND	Norwegian	Sagittal⁺⁺	EL/P	ADAMTSL4	c.767_786del, c.767_786del	p.Gln256Profs38, p.Gln256Profs38	0.001219
[27]	F	10 wk	10 mo	ND	Right coronal	Bilateral EL	ADAMTSL4	c.767_786del, c.767_786del	p.Gln256Profs38, p.Gln256Profs38	0.001219
[29, 32]	F	<2 yr	3 yr	Dutch	Metopic	Bilateral EL	ADAMTSL4	c.767_786del, c.2254C > T	p.Gln256Profs38, p.Gln752	0.001219, 0.000004059
[29, 32]	F	7 mo	3 yr	Dutch	Sagittal	Bilateral EL	ADAMTSL4	c.767_786del, c.2254C > T	p.Gln256Profs38, p.Gln752	0.001219, 0.000004059

Previously published, genotypically unsolved (non-Marfanoid) patients with CS/EL
[36]	M	<6 yr	23 yr	ND	Coronal	Bilateral EL	Unknown
[35]	F	Birth	4 mo	ND	Left coronal	Bilateral EL	Unknown
[33]	ND	<6 yr	<6 yr	Turkish	Parietal/tempoparietal	Bilateral EL	Unknown
[34]	M	<6 yr	<6 yr	French	Sagittal (scaphocephaly)	Bilateral EL	Unknown

Previously published patients with CS/EL as features of early-onset Marfan syndrome
[26]	F	<7 yr	<7 yr	ND	Scaphocephaly with craniosynostosis	EL	FBN1	c.3668G > A	p.C1223Y	Not listed
[25]	M	8 mo	6 yr	ND	Sagittal	Bilateral EL	FBN1	c.3302G > A	p.Y1101C	Not listed

M, male; F, female; ND, not described; CS, craniosynostosis; EL, ectopia lentis; EL/P, ectopia lentis et pupillae; MAF, minor allele frequency. Age indicates age at diagnosis of CS and EL, respectively. ⁺Sister of patient 2 has the same genotype but presents only with EL/P. ⁺⁺Detail ascertained through personal correspondence with author.