Ptosis: A Clinical Sign of Many Dimensions

Background/Purpose: Blepharoptosis (ptosis) is a common, easily appreciated sign which can occurred isolated or as a feature of syndromal disorders. Ptosis has many dimensions, ranging from hereditary to sporadic, acute to chronic, unilateral to bilateral, and progressive to nonprogressing.

Methods: Here, we describe a male infant from Bosnia with bilateral ptosis, dysphagia, and recurring airway infections. He was born at term, small for gestational age (birth weight 2,920 g, P. 4). Neurological (including cerebral MRI) and metabolic assays were performed without pathologic findings.

Upon initial presentation (7 months), we saw an infant with muscular hypotonia, failure to thrive [weight 6.38 kg (P. 5), length 66 cm (P. 50), head circumference: 44 cm (P. 44)], bilateral ptosis, and deep set ears comparable to the Noonan spectrum.

Results: Comprehensive genetic diagnostics including karyogram (ISCN 550), Microarray (Infinium CytoSNP-850K), PTPN11 (complete sequencing), Noonan Panel (BRAF, KRAS, RAF1, RIT1, SOS1, and SPRED1) were all without pathological findings. Sequencing of congenital myasthenic syndromes genes (CMS) revealed a pathological, homozygous variant in CHRNE c.1327del p.(GIu443Lysfs*64). Acetylcholine receptors (AChR) at neuromuscular junctions are pentameric protein complexes. CHRNE codes for an epsilon subunit of AChR. Mutations in the epsilon subunit are associated with congenital myasthenic syndromes (Croxen et al 1998). Neonatal presentation comprises stridor, respiratory insufficiency with sudden onset of apnea, generalized weakness and difficulties feeding (Kinali et al 2008).

Conclusion: Ptosis is a clinical sign of several disorders with overlapping phenotypes. Accurate molecular diagnostics identifies distinct syndromes and informs therapeutic strategies, e.g., patients with CMS benefit from AChE inhibitors and/or the potassium channel blockers.

Publication History

Article published online:
28 October 2021