Raynaud phenomenon

Angiopathy, Hereditary, with Nephropathy, Aneurysms, and Muscle Cramps

Clinical Characteristics
Ocular Features: 

Tortuosity of second and third order arterioles is usually present bilaterally but does not involve first order branches.  Intraretinal hemorrhages may also be seen and are sometimes associated with minor stress and trauma.  No fluorescein leakage is present.  Vision usually remains good but transient vision loss may be reported if the retinal hemorrhages involve the fovea and parafoveal areas.

Systemic Features: 

Nail bed capillaries may appear tortuous.  Aneurysms of the internal carotid and middle cerebral arteries can be present and cerebrovascular accidents sometimes occur.  Brain imaging may show degrees of leukoencephalopathy.  Large renal cysts, mild hematuria both microscopic and gross, and mild renal failure are sometimes seen.  Some patients experience Raynaud phenomena.  Muscle cramps lasting seconds to hours are not uncommon.  Some patients have supraventricular cardiac arrhythmias.

Alterations in basement membrane morphology can be seen on electron microscopy in many areas of the body but that of the glomeruli is normal even though the filtration rate is decreased.

Genetics

This is an autosomal dominant condition as the result of heterozygous mutations in COL4A1 (13q34).  Mutations in the same gene have also been found in a simpler autosomal dominant disease known as Retinal Arteriolar Tortuosity (180000).  The latter may be an allelic condition or the same disorder.

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is available for the underlying disease although symptomatic relief for cramps, arrhythmias, and renal failure may be beneficial.

References
Article Title: 

Tenorio Syndrome

Clinical Characteristics
Ocular Features: 

The eyebrows appear bushy.  Inflammation of the limbus and keratoconjunctivitis sicca are often present and reported to resemble Sjogren syndrome.

Systemic Features: 

Infants appear large at birth with a large forehead and macrocephaly.  Birth weight, length, and head circumference are usually above the 97th percentile. The mandible appears large and the lips are full and ‘fleshy’.  Dentition is delayed.  Recurrent stomatitis and gastroesophageal reflux have been noted.  Closure of the fontanels is delayed.  Hypotonia and hyperflexible joints can be a feature.

Multiple brain anomalies have been described including cortical atrophy, dilated and asymmetrical ventricles, and mild hydrocephalus.  Psychomotor development and milestones are delayed.  Intellectual disabilities, syncope, hypoglycemia, seizures, apneic episodes, mood anomalies, abnormal gait, and general clumsiness may be present.  There was considerable clinical variation among the six reported patients. 

Genetics

Heterozygous mutations in RNF125 (18q12.1) are responsible for this syndrome. 

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 

A new overgrowth syndrome is due to mutations in RNF125

Tenorio J, Mansilla A, Valencia M, Martinez-Glez V, Romanelli V, Arias P, Castrejon N, Poletta F, Guillen-Navarro E, Gordo G, Mansilla E, Garcia-Santiago F, Gonzalez-Casado I, Vallespin E, Palomares M, Mori MA, Santos-Simarro F, Garcia-Minaur S, Fernandez L, Mena R, Benito-Sanz S, del Pozo A, Silla JC, Ibanez K, Lopez-Granados E, Martin-Trujillo A, Montaner D; SOGRI Consortium, Heath KE, Campos-Barros A, Dopazo J, Nevado J, Monk D, Ruiz-Perez VL, Lapunzina P. A new overgrowth syndrome is due to mutations in RNF125. Hum Mutat. 2014 Dec;35(12):1436-41.

PubMed ID: 
25196541
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