bruising

Chédiak-Higashi Syndrome

Clinical Characteristics
Ocular Features: 

The ocular hypopigmentation and visual function deficits in Chediak-Higashi syndrome resembles that of other types of albinism.  The iris has transillumination defects and the retina is hypopigmented.  Patients are photophobic and often have nystagmus.  Due to the early mortality of many patients, vision is difficult to measure, but is said to range from normal to near normal.  Hair bulb incubations studies show normal pigmentation.

A  subset of patients with later onset of disease has been reported to have optic atrophy, thinning of the nerve fiber layer, and a central scotoma.

Systemic Features: 

This is a form of albinism with other systemic features such as adenopathy, hepatosplenomegaly, neutropenia, and susceptibility to infection (especially gram positive organisms).  The hypopigmentation is evident at birth but may be patchy.  The hair has been described as having a blue-green metallic sheen.  It may also be sparse.  Patients have an increased risk of leukemia and lymphoma-like disease.  Peripheral sensory-motor neuropathy and ataxia are common in older individuals.  Thrombocytopenia can lead to easy bruising and extensive bleeding.  Neutrophils are often few in number and deficient in chemotactic and bacterial activity.  Pyoderma and peridontitis can be severe.  Survival without treatment is between 3 and 4 years but those who survive eventually develop lymphohistiocytic infiltration of major organs, bone marrow and peripheral nerves as young adults.

Giant peroxidase-positive inclusions in white blood cells are diagnostic.

Genetics

This is an autosomal recessive disorder caused by mutations in the LYST gene (1q42.1-q42.2) causing defects in vesicle trafficking.

Hermansky-Pudlak syndrome (214500) is another form of hypopigmentation with serious systemic manifestations.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Bone marrow transplantation can prolong life but neurologic symptoms often develop in those who survive.  Low-vision aids can be helpful.  Infections, of course, should be promptly and vigorously treated.

References
Article Title: 

Optic neuropathy in late-onset neurodegenerative Chédiak-Higashi syndrome

Desai N, Weisfeld-Adams JD, Brodie SE, Cho C, Curcio CA, Lublin F, Rucker JC. Optic neuropathy in late-onset neurodegenerative Chediak-Higashi syndrome. Br J Ophthalmol. 2015 Aug 25. pii: bjophthalmol-2015-307012. doi: 10.1136/bjophthalmol-2015-307012. [Epub ahead of print].

PubMed ID: 
26307451

Chédiak-Higashi syndrome

Kaplan J, De Domenico I, Ward DM. Chediak-Higashi syndrome. Curr Opin Hematol. 2008 Jan;15(1):22-9. Review. PubMed PMID: 18043242.

PubMed ID: 
18043242

Ehlers-Danlos Syndrome, Type VIA

Clinical Characteristics
Ocular Features: 

The globe is thin and fragile and ruptures easily.  This results from scleral fragility which is in contrast to type VIB EDS  (229200) in which the cornea seems to be more fragile.  Retinal detachment is always a risk but no quantitative assessment can be made since early case reports did not always provide good classification of EDS types.  Other ocular abnormalities such as keratoconus and structural changes in the cornea are less common but frequent changes in classification and lack of genotyping in early cases make definitive clinical correlations difficult.

Systemic Features: 

The primary clinical manifestations of this form (VIA) of Ehlers-Danlos syndrome are extraocular.   The skin is soft, thin, easily extensible, and bruises easily.  The joints are highly flexible with a tendency to dislocate.  Arterial ruptures are not uncommon, often with severe consequences.  Scoliosis begins almost at birth and often progresses to severe kyphoscoliosis.  Patients are floppy (hypotonic).  Intellect is normal and there are generally no developmental delays.  Thirty per cent of infants have a club foot at birth.

Genetics

This an autosomal recessive disorder caused by molecular defects in the PLOD1 gene (1p36.3-p36.2).  The gene product is an enzyme, lysyl hydroxylase 1, important for the normal crosslinking of collagen. Mutations in PLOD1 may result in hydroxylase dysfunction with abnormal hydroxylation of lysine, weakened crosslinks, and fragile tissue.  

The classification of Ehlers-Danlos disease is under constant revision as new mutations and clinical subtypes are found (see 130000).

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Joint dislocations, ocular trauma and vascular ruptures require prompt attention.  Longevity is not impacted by this syndrome.

References
Article Title: 
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