Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children.

This corrects the article DOI: 10.1038/tp.2017.27.

Premature primary tooth eruption in cognitive/motor-delayed ADNP-mutated children.

A major flaw in autism spectrum disorder (ASD) management is late diagnosis. Activity-dependent neuroprotective protein (ADNP) is a most frequent de novo mutated ASD-related gene. Functionally, ADNP protects nerve cells against electrical blockade. In mice, complete Adnp deficiency results in dysregulation of over 400 genes and failure to form a brain. Adnp haploinsufficiency results in cognitive and social deficiencies coupled to sex- and age-dependent deficits in the key microtubule and ion channel pathways. Here, collaborating with parents/caregivers globally, we discovered premature tooth eruption as a potential early diagnostic biomarker for ADNP mutation. The parents of 44/54 ADNP-mutated children reported an almost full erupted dentition by 1 year of age, including molars and only 10 of the children had teeth within the normal developmental time range. Looking at Adnp-deficient mice, by computed tomography, showed significantly smaller dental sacs and tooth buds at 5 days of age in the deficient mice compared to littermate controls. There was only trending at 2 days, implicating age-dependent dysregulation of teething in Adnp-deficient mice. Allen Atlas analysis showed Adnp expression in the jaw area. RNA sequencing (RNAseq) and gene array analysis of human ADNP-mutated lymphoblastoids, whole-mouse embryos and mouse brains identified dysregulation of bone/nervous system-controlling genes resulting from ADNP mutation/deficiency (for example, BMP1 and BMP4). AKAP6, discovered here as a major gene regulated by ADNP, also links cognition and bone maintenance. To the best of our knowledge, this is the first time that early primary (deciduous) teething is related to the ADNP syndrome, providing for early/simple diagnosis and paving the path to early intervention/specialized treatment plan.

Autosomal recessive blepharophimosis, ptosis, V-esotropia, syndactyly and short stature.

A recessively inherited syndrome of blepharophimosis and ptosis with weakness of extraocular and frontal muscles is reported in six members of three related kindreds. Prognathism, synophrys and thick eyebrows added to a typical facial appearance. Additional findings included short stature, borderline head circumference and toe syndactyly. Borderline mental retardation and anosmia were found in one patient. The clinical features and the mode of inheritance distinguish this syndrome from other blepharophimosis and ptosis syndromes.

Long-term follow-up of traumatic unilateral superior oblique palsy.

Twenty-four cases of traumatic unilateral superior oblique palsy were followed-up during a mean period of 5.3 years. Hypertropia in the primary position and a positive Bielschowsky test were present in 100% of the cases, compensating head posture in 71%, and excyclotorsion in 25%. Six patients needed surgical correction; 18 were cured spontaneously during a mean period of 9.2 months.

Retinal damage after argon laser iridotomy.

We conducted a prospective clinical study to evaluate potential retinal damage after argon laser iridotomy in 25 eyes of 22 patients with primary chronic angle-closure glaucoma. Kinetic perimetry and ophthalmoscopy showed no detectable damage. Iridotomy required a mean of 11.4 +/- 10 joules to achieve a patent coloboma of 200 micron after one to three sessions. Dark-prone and mydriasis tests were performed one month after surgery. Pilocarpine was discontinued in all cases. Both static perimetry and fluorescein angiography of the midperiphery corresponding to the meridian of laser coloboma done six months after surgery showed focal damage. There was no damage in control tests of the same eyes in an opposite area of the retina.

Evaluation of laser iridectomy in angle-closure glaucoma: provocative tests.

An argon laser iridectomy was performed on 18 eyes of 14 patients with closed-angle glaucoma. The intraocular pressure (IOP) was controlled in all but one eye within normal limits. Variable amounts of pigment were found on gonioscopy in all cases. The mydriasis test was positive in one eye (5.5%) after homatropine and in 5 eyes (28%) after tropicamide drops. 80% of the positive results occurred in lightly pigmented irides. The dark-prone position test was positive in 7 eyes (38%), 71% of the positive results occurring in heavily pigmented irides. Tomography was also performed; the possibility of trabecular damage is discussed.

Bilateral optic neuropathy due to combined ethambutol and isoniazid treatment.

The case of a 40-year-old patient who underwent an unsuccessful cadaver kidney transplantation and was treated with ethambutol and isoniazid is reported. A bilateral retrobulbar neuropathy with an unusual central bitemporal hemianopic scotoma was found. Ethambutol was stopped and only small improvement of the visual acuity followed. Isoniazid was discontinued later, followed by a dramatic improvement in the visual acuity. The hazards of optic nerve toxicity due to ethambutol are known. We emphasize the potential danger in the use of ethambutol and isoniazid.