alacrima

HELIX Syndrome

Clinical Characteristics
Ocular Features: 

Alacrimia has been confirmed with Schirmer test strips but the ocular examination has been described as otherwise normal.

Systemic Features: 

All patients have anhidrosis resulting in alacrima and xerostomia with heat intolerance.  Nails and hair are normal.  Muscle weakness, heart palpitations, and post-exertional cramping may be experienced with mild exercise beginning in the first decade.  Polydipsia and polydipsia may be additional complaints.  Severe dental enamel wear is often evident.  The skin has a fine, white scaliness.  Adolescent-onset nephrocalcinosis has been reported in some patients.

The majority of patients have elevated serum Mg++ levels.  Mild renal failure occurs with loss of NaCl and secondary hyperaldosteronism and hypokalemia.

Genetics

Homozygous mutations in the CLDN10 gene (13q32.1) are responsible for this disorder.  Consanguinity is present in some families.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Dental resins has been reported to be beneficial as a protective coating of the teeth.  Ocular evaluations for corneal damage from alacrima have not been reported but moisturizing preparations should be used as indicated. 

References
Article Title: 

Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome

Hadj-Rabia S, Brideau G, Al-Sarraj Y, Maroun RC, Figueres ML, Leclerc-Mercier S, Olinger E, Baron S, Chaussain C, Nochy D, Taha RZ, Knebelmann B, Joshi V, Curmi PA, Kambouris M, Vargas-Poussou R, Bodemer C, Devuyst O, Houillier P, El-Shanti H. Multiplex epithelium dysfunction due to CLDN10 mutation: the HELIX syndrome. Genet Med. 2017 Aug 3. doi: 10.1038/gim.2017.71. [Epub ahead of print].

PubMed ID: 
28771254

Dysautonomia, Familial

Clinical Characteristics
Ocular Features: 

Decreased lacrimation is the major ocular feature in this syndrome and it may be sufficiently severe to result in corneal damage.  Decreased corneal sensation as part of the generalized neuropathy likely plays a role.  Epithelial defects are slow to heal and their chronic presence along with neurotrophic ulcers often leads to corneal thinning.  The blink rate is reduced, especially during crises.  The lid fissures are abnormally wide contributing further to corneal drying.  The pupillary light response time may be prolonged.  Miosis follows administration of methacholine chloride.  Optic neuropathy with pallor is often present.

Systemic Features: 

Vasomotor instability and sensory neuropathy are among the outstanding signs in familial dysautonomia.  Episodic hypertension alternating with hypotension, hyperhidrosis, cyclic vomiting, and skin blotching are common.  Deep tendon reflexes are often diminished or absent and there is a general indifference to pain and temperature.  The lingual fungiform papillae are missing resulting in taste disturbances.  Emotional instability and impaired coordination are frequently seen.  Emotional or physical stress can precipitate dysautonomic crises with nausea, vomiting, agitation, tachycardia, and hypertension.  Physical growth may be slow and scoliosis is common.  Patients are susceptible to self-injury.

Arrested development in the sensory and autonomic nervous systems results in a reduction in nonmyelinated nerve fibers as well as a reduction in small diameter myelinated axons.  Sympathetic ganglia are abnormally small in size.  There is hypersensitivity to both sympathomimetic and parasympathomimetic drugs.

Genetics

Hereditary sensory and autonomic neuropathy type III results from mutations in the IKBKAP gene (9q31).  It is an autosomal recessive condition.

A brief report describes 4 sibs with a clinical picture similar to familial dysautonomia with a mutation in DST (6p12.1).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for the general disease but therapies are available for specific problems.  Good hydration, assisted ventilation during sleep, and liberal use of tear substitutes can be helpful.  Lacrimal ointments and lid taping during sleep are advised.  Punctal occlusion should be considered in selected cases.  Corneal ulcers or slow healing epithelial defects can be treated with a temporary tarsorrhaphy.   

Patients with familial dysautonomia are at increased risk of intraoperative cardiorespiratory complications which can be reduced by adequate hydration, reduced use of volatile anesthetic agents, and attention to postoperative ventilation.

References
Article Title: 
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