Longitudinal ophthalmic findings in a child with Helsmoortel-Van der Aa Syndrome

Abstract

PurposeWe present the first detailed ophthalmic description of a child with Helsmoortel-Van der Aa Syndrome (HVDAS), including longitudinal follow-up and analysis.ObservationsAfter extensive workup, a young child with poor visual behavior, hypotonic cerebral palsy, intellectual disability, and global developmental delay was found to have a heterozygous de novo mutation in the ADNP gene and diagnosed with HVDAS. Ophthalmic findings were remarkable for progressive nystagmus, macular pigment mottling, mild foveal hypoplasia with abnormal macular laminations, persistent rod dysfunction with electronegative waveform, and progressive cone degeneration.Conclusions and importancePatients with HVDAS are known to have abnormal visual behavior due to refractive or cortical impairment. However, we present the first description, to our knowledge, of an association with retinal mal-development and degeneration. Thus, patients with HVDAS should be referred for ophthalmic genetics evaluation, and HVDAS should be on the differential diagnosis for young children with global developmental delay who present with nystagmus, rod and cone dysfunction with electronegative waveform, and relative lack of severe structural degeneration on optical coherence tomography.

Activity-Dependent Neuroprotective Protein (ADNP): An Overview of Its Role in the Eye

“…In another paper, a detailed description of the ophthalmologic condition of an HVDAS-affected child bearing an ADNP gene mutation, was provided. This patient showed various eye dysfunctions mainly affecting the retina [ 92 ]. This evidence, thus, further supports the important protective and regenerative effects of ADNP in the eye.…”

Inherited Eye Diseases with Retinal Manifestations through the Eyes of Homeobox Genes

“…ADNP is classified as one of three most prevalent autism-causing genes [67]. Ophthalmic findings were remarkable for progressive nystagmus, macular pigment mottling, mild foveal hypoplasia with abnormal macular laminations, persistent rod dysfunction with electronegative waveform, and progressive cone degeneration [68]. HVDAS with ocular anomalies is associated with specific mutations clustering within the "bipartite nuclear localization signal" [69].…”

Le syndrome ADNP (protéine neuroprotectrice dépendante de l’activité) lié à la déficience intellectuelle et aux troubles du spectre autistique : une revue de la littérature

“…Des comportements de recherche sensorielle sont également retrouvés, ainsi que des troubles du sommeil. Le syndrome ADNP peut s'accompagner d'une hypotonie ou, rarement, d'une hypertonie, d'épilepsie, de malformations cranio-cérébrales, d'une dysmorphie faciale distincte (front proéminent, ligne capillaire haute, fentes palpébrales orientées en haut ou en bas, ptosis voire parfois blépharophimosis (27)(28)31), ensellure nasale marquée, lèvre supérieure fine, pavillons des oreilles déformés), de problèmes sensoriels, principalement visuels (trouble de la réfraction, strabisme, nystagmus, colobome, anomalies rétiniennes (11,26)) et occasionnellement auditifs (21). Des troubles gastro-intestinaux sont très fréquents (difficultés à s'alimenter dans la petite enfance, reflux gastro-oesophagien, constipation).…”