apnea

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

Homocystinuria, MTHFR Deficiency

Clinical Characteristics
Ocular Features: 

The ocular signs in MTHFR deficiency are likely similar to those found in beta-synthase deficiency (236200) but no comparative study has been reported.  Ectopia lentis is common and the high mobility of the lens carries a significant risk of pupillary block glaucoma and migration into the anterior chamber.

Systemic Features: 

There is a wide range in clinical disease in MTHFR deficiency but the neurological signs and the progressive of disease seem to be more aggressive than in beta-synthase deficiency (236200) . Neonates may have seizures and failure to thrive but other affected patients may live to adulthood without symptoms.  Early death from neurological complications is more common and the mental retardation is apparently more severe.  There is a serious risk for thromboembolic events which may be life-threatening.  Hyperhomocyteinemia and low plasma methionine are present as is increased homocystine in urine.

Genetics

Mutations in MTHFR (1p36.3) are responsible for this form of homocystinuria.  Another form, beta-synthase deficiency (236200), is caused by a mutation in the CBS  gene (21q22.3).  This is an autosomal recessive disorder.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Administration of betaine has been reported to reduce the neurological disease but it must be started early before brain damage occurs.  It does not correct hyperhomocysteinemia nor does it correct CNS MTHFR deficiency.  It has also been reported that betaine in combination with folic acid and cobalamin can prevent symptoms.

References
Article Title: 

Mutation Update and Review of Severe MTHFR

Froese DS, Huemer M, Suormala T, Burda P, Coelho D, Gueant JL, Landolt MA,
Kozich V, Fowler B, Baumgartner MR. Mutation Update and Review of Severe MTHFR
Deficiency. Hum Mutat. 2016 Feb 13.

PubMed ID: 
2687264
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