Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome

van Rahden, Vanessa A; Rau, Isabella; Fuchs, Sigrid; Kosyna, Friederike K; de Almeida, Hiram Larangeira; Fryssira, Helen; Isidor, Bertrand; Jauch, Anna; Joubert, Madeleine; Lachmeijer, Augusta M A; Zweier, Christiane; Moog, Ute; Kutsche, Kerstin

doi:10.1186/1750-1172-9-53

Orphanet Journal of Rare Diseases

Table 1 Collection of molecular and clinical data of 6 patients with MLS syndrome

From: Clinical spectrum of females with HCCS mutation: from no clinical signs to a neonatal lethal form of the microphthalmia with linear skin defects (MLS) syndrome

Patients	HCCS mutation	XCI^a	Dermatologic findings	Ocular findings			Cardiac defects	CNS anomalies	Microcephaly	Developmental delay/intellectual disability	Facial dysmorphism	Short stature	Other anomalies
Patients	HCCS mutation	XCI^a	Dermatologic findings	Microphthalmia/anophthalmia	Sclerocornea/corneal opacity	Others	Cardiac defects	CNS anomalies	Microcephaly	Developmental delay/intellectual disability	Facial dysmorphism	Short stature	Other anomalies
1	ish del(X)(p22.2p22.2), interstitial deletion of ~850 kb including HCCS inherited	100:0	―	bilateral microphthalmia	bilateral sclerocornea	gracile optic nerves and chiasma, bilateral microcornea, ectopic pupil (right), coloboma iris (right), anterior eye chamber defect	―	very mild delay in myelination	―	―	small deep-set eyes	―	―
7 years Dutch		100:0	―	bilateral microphthalmia	bilateral sclerocornea		―	very mild delay in myelination	―	―	small deep-set eyes	―	―
2	c.589C > T (p.R197) de novo*	98:2	linear skin defects on the neck	microphthalmia (Peter’s anomaly with adherence of iris on cornea and anterior chamber) (right), anophthalmia (left)	unilateral sclerocornea and corneal opacity (right)	optic nerve hypoplasia (left)	ventricular tachycardia, poor contraction of left ventricle, histiocytoid cardiomyopathy, eosinophilic cell infiltration	abnormal myelination, hypoplastic corpus callosum, absence of septum pellucidum	―	n.a.	―	-3 SD^b	―
Died at 4 months French	c.589C > T (p.R197) de novo*	98:2	linear skin defects on the neck		unilateral sclerocornea and corneal opacity (right)	optic nerve hypoplasia (left)			―	n.a.	―	-3 SD^b	―
3	c.[=/524_525delAG] (p.[=/E175Vfs30]) de novo*	82:18	―	unilateral microphthalmia (left)	unilateral sclerocornea (left)	unilateral cornea plana (left)	―	n.d.	―	mild motor delay^c	mild facial asymmetry, prominent philtrum	―	mild muscular hypotonia, sacral dimple
3 years German	c.[=/524_525delAG] (p.[=/E175Vfs30]) de novo*	82:18	―	unilateral microphthalmia (left)	unilateral sclerocornea (left)	unilateral cornea plana (left)	―	n.d.	―	mild motor delay^c	mild facial asymmetry, prominent philtrum	―	mild muscular hypotonia, sacral dimple
4	46,X,del(X)(p22) de novo	100:0	linear skin defects on the face, neck, hand (right) and foot (left)	severe bilateral microphthalmia	corneal opacity	aphakia	―	agenesis of corpus callosum	-4.86 SD^d	+	mild prognathism	48 cm (0.1 cm <3rd centile)^e; -3.33 SD^d	―
4 years German	46,X,del(X)(p22) de novo	100:0		severe bilateral microphthalmia	corneal opacity	aphakia	―	agenesis of corpus callosum	-4.86 SD^d	+	mild prognathism	48 cm (0.1 cm <3rd centile)^e; -3.33 SD^d	―
5	46,X,del(X)(p22) de novo	100:0	linear skin defects on the face, small hemangiomas on face, neck and right hand	microphthalmia (left), anophthalmia (right)	unilateral sclerocornea (left)	―	―	―	49 cm (3rd centile)^f	+	long thin face, mild prognathism, depressed nasal bridge, microdontia, high palate, low-set and posteriorly rotated ears	105 cm (3rd centile)^g	deafness (right), anal atresia with ectopic anus and fistula, clinodactyly of the fifth finger
10 years Greek	46,X,del(X)(p22) de novo	100:0		microphthalmia (left), anophthalmia (right)	unilateral sclerocornea (left)	―	―	―	49 cm (3rd centile)^f	+		105 cm (3rd centile)^g
6	interstitial deletion of ≥3 Mb including HCCS^h	100:0	linear skin defects on the face	bilateral microphthalmia	bilateral sclerocornea	―	―	―	―	―	―	67 cmⁱ	intralesional absence of sebaceous glands (dermatoscopic examination)
1 year Brazilian	interstitial deletion of ≥3 Mb including HCCS^h	100:0	linear skin defects on the face	bilateral microphthalmia	bilateral sclerocornea	―	―	―	―	―	―	67 cmⁱ

Legends: n.a.: not applicable; n.d.: not determined; SD: standard deviation; ―: absent; +: present; ^a: determined in leukocytes; ^b: at the age of 3 months; ^c: at the age of 11 months; ^d: at the age of 3 years; ^e: at birth; ^f: at the age of 7 years; ^g: at the age of 6 years; ^h: inheritance of the interstitial microdeletion could not be determined as the father was not available. ⁱ: at the age of 9 months.

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ISSN: 1750-1172

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