Strømme Syndrome Clinical CharacteristicsOcular Features: The core complex of Stromme syndrome consists of intestinal atresia and ocular abnormalities of the anterior segment. The ocular anomalies consist of variable amounts of angle dysgenesis, anterior synechiae, corneal leukoma, iris colobomas and hypoplasia, sclerocornea, cataracts, and sometimes microcornea. However, microphthalmia, tortuous retinal vessels, and optic nerve hypoplasia may also be present. Hypertelorism and deep-set eyes have been described. Glaucoma has not been reported. Only about 10 cases have been reported since Stromme 's first report in 1993. Most patients have been too young for reliable acuity testing. Systemic Features: The phenotype is highly variable. The ears are often large and low-set. Microcephaly is often present along with a cleft palate and micrognathia. The intestinal atresia seems to involve the jejunum primarily and is usually surgically correctable. The duodenum may also be involved and intestinal malrotation has been described. Myopathic changes in the myocardium have been seen along with small cardiomyoctes. Microcephaly seems to be progressive. Short stature has been noted and the amount of developmental delay is highly variable. Renal hypodysplasia and hydronephrosis have been described. Some patients seem to develop and function almost normally while more severely affected individuals may not live beyond early infancy or childhood. GeneticsCompound heterozygous mutations in the CENPF gene (1q41) segregate with this condition. Pedigree: Autosomal recessiveTreatmentTreatment Options: Infants do well following intestinal surgery. Ocular surgery has not been reported. ReferencesArticle Title: Stromme Syndrome: New Clinical Features Stromme Syndrome: New Clinical Features Bayram Ali Dorum, Irmak Tanal Sambel, Hilal Ozkan, Irfan Kiristioglu, Nilgun Koksal APSP J Case Rep. 2017 Mar-Apr; 8(2): 14. Published online 2017 Mar 18. PubMed ID: 5371687 Stromme Syndrome is a Ciliary Disorder Caused by Mutations in CENPF Filges I, Bruder E, Brandal K, Meier S, Undlien DE, Waage TR, Hoesli I, Schubach M, de Beer T, Sheng Y, Hoeller S, Schulzke S, Rosby O, Miny P, Tercanli S, Oppedal T, Meyer P, Selmer KK, Stromme P. Stromme Syndrome is a Ciliary Disorder Caused by Mutations in CENPF. Hum Mutat. 2016 Jan 28. doi: 10.1002/humu.22960. [Epub ahead of print]. PubMed ID: 26820108 Jejunal atresia and anterior chamber anomalies: Further delineation of the Stromme syndrome Castori M, Laino L, Briganti V, Pedace L, Zampini A, Marconi M, Grammatico B, Buffone E, Grammatico P. Jejunal atresia and anterior chamber anomalies: Further delineation of the Stromme syndrome. Eur J Med Genet. 2010 May-Jun;53(3):149-52. PubMed ID: 20219704 Exclusion of a PAX6, FOXC1, PITX2, and MYCN mutation in another patient with apple peel intestinal atresia, ocular anomalies and microcephaly and review of the literature van Bever Y, van Hest L, Wolfs R, Tibboel D, van den Hoonaard TL, Gischler SJ. Exclusion of a PAX6, FOXC1, PITX2, and MYCN mutation in another patient with apple peel intestinal atresia, ocular anomalies and microcephaly and review of the literature. Am J Med Genet A. 2008 Feb 15;146A(4):500-4. Review. PubMed ID: 18203155 Apple peel intestinal atresia in siblings with ocular anomalies and microcephaly Stromme P, Dahl E, Flage T, Stene-Johansen H. Apple peel intestinal atresia in siblings with ocular anomalies and microcephaly. Clin Genet. 1993 Oct;44(4):208-10. PubMed ID: 8261651 Read more about Strømme Syndrome
Stromme Syndrome: New Clinical Features Stromme Syndrome: New Clinical Features Bayram Ali Dorum, Irmak Tanal Sambel, Hilal Ozkan, Irfan Kiristioglu, Nilgun Koksal APSP J Case Rep. 2017 Mar-Apr; 8(2): 14. Published online 2017 Mar 18. PubMed ID: 5371687
Stromme Syndrome is a Ciliary Disorder Caused by Mutations in CENPF Filges I, Bruder E, Brandal K, Meier S, Undlien DE, Waage TR, Hoesli I, Schubach M, de Beer T, Sheng Y, Hoeller S, Schulzke S, Rosby O, Miny P, Tercanli S, Oppedal T, Meyer P, Selmer KK, Stromme P. Stromme Syndrome is a Ciliary Disorder Caused by Mutations in CENPF. Hum Mutat. 2016 Jan 28. doi: 10.1002/humu.22960. [Epub ahead of print]. PubMed ID: 26820108
Jejunal atresia and anterior chamber anomalies: Further delineation of the Stromme syndrome Castori M, Laino L, Briganti V, Pedace L, Zampini A, Marconi M, Grammatico B, Buffone E, Grammatico P. Jejunal atresia and anterior chamber anomalies: Further delineation of the Stromme syndrome. Eur J Med Genet. 2010 May-Jun;53(3):149-52. PubMed ID: 20219704
Exclusion of a PAX6, FOXC1, PITX2, and MYCN mutation in another patient with apple peel intestinal atresia, ocular anomalies and microcephaly and review of the literature van Bever Y, van Hest L, Wolfs R, Tibboel D, van den Hoonaard TL, Gischler SJ. Exclusion of a PAX6, FOXC1, PITX2, and MYCN mutation in another patient with apple peel intestinal atresia, ocular anomalies and microcephaly and review of the literature. Am J Med Genet A. 2008 Feb 15;146A(4):500-4. Review. PubMed ID: 18203155
Apple peel intestinal atresia in siblings with ocular anomalies and microcephaly Stromme P, Dahl E, Flage T, Stene-Johansen H. Apple peel intestinal atresia in siblings with ocular anomalies and microcephaly. Clin Genet. 1993 Oct;44(4):208-10. PubMed ID: 8261651
Peters-Plus Syndrome Clinical CharacteristicsOcular Features: Peters anomaly (306229) usually occurs as an isolated ocular malformation and is often unilateral. However, in some patients with bilateral involvement it is part of a systemic syndrome or other congenital conditions such as chromosomal deletions and the fetal alcohol syndrome. It is called Peters Plus syndrome in the condition described here because of the association of a specific combination of systemic features. The ocular features are consistent with dysgenesis of the anterior chamber. The clinical picture is highly variable but generally consists of iris adhesions to the cornea centrally (classical Peters anomaly), occasionally lenticular adhesions as well, and thinning of the central corneal stroma. As a result, the cornea may become edematous, cataracts may develop, and glaucoma is common. Systemic Features: Peters-plus syndrome consists of Peters anomaly plus various degrees of developmental delays and intellectual deficits, short digits and short stature, and cleft lip and palate. The facies is said to be characteristic due to a prominent forehead, narrow palpebral fissures, and a cupid's bow-shaped upperlip. There may be preauricular pits present and the neck is often broad. The ears may be prominent. Congenital heart defects are present in a third of patients and a few have genitourinary anomalies. GeneticsThis is an autosomal recessive disorder of glycosylation caused by a mutation in the B3GALTL gene on chromosome 13 (13q12.3). At least some patients have a splicing mutation in this gene leading to a skipping of exon 8. Pedigree: Autosomal recessiveTreatmentTreatment Options: Treatment is directed at sight preservation by correcting the major ocular defects such as glaucoma and iridocorneal adhesions. Corneal transplants and cataract removal are sometimes required. Releasing the anterior synechiae can lead to significant clearing of the corneal edema. Growth hormone replacement therapy may be beneficial. ReferencesArticle Title: First functional analysis of a novel splicing mutation in the B3GALTL gene by an ex vivo approach in Tunisian patients with typical Peters plus syndrome Mahmoud AB, Siala O, Mansour RB, Driss F, Baklouti-Gargouri S, Mkaouar-Rebai E, Belguith N, Fakhfakh F. First functional analysis of a novel splicing mutation in the B3GALTL gene by an ex vivo approach in Tunisian patients with typical Peters plus syndrome. Gene. 2013 Aug 14. [Epub ahead of print]. PubMed ID: 23954224 Novel B3GALTL mutations in classic Peters Plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes Weh E, Reis LM, Tyler RC, Bick D, Rhead WJ, Wallace S, McGregor TL, Dills SK, Chao MC, Murray JC, Semina EV. Novel B3GALTL mutations in classic Peters Plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes. Clin Genet. 2013 Jul 24. [Epub ahead of print]. PubMed ID: 23889335 Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase Lesnik Oberstein SA, Kriek M, White SJ, Kalf ME, Szuhai K, den Dunnen JT, Breuning MH, Hennekam RC. Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase. Am J Hum Genet. 2006 Sep;79(3):562-6. Erratum in: Am J Hum Genet. 2006 Nov;79(5):985. PubMed ID: 16909395 The Peters' plus syndrome: a review Maillette de Buy Wenniger-Prick LJ, Hennekam RC. The Peters' plus syndrome: a review. Ann Genet. 2002 Apr-Jun;45(2):97-103. Review. PubMed ID: 12119218 Peters' anomaly and associated congenital malformations Traboulsi EI, Maumenee IH. Peters' anomaly and associated congenital malformations. Arch Ophthalmol. 1992 Dec;110(12):1739-42. PubMed ID: 1463415 Read more about Peters-Plus Syndrome
First functional analysis of a novel splicing mutation in the B3GALTL gene by an ex vivo approach in Tunisian patients with typical Peters plus syndrome Mahmoud AB, Siala O, Mansour RB, Driss F, Baklouti-Gargouri S, Mkaouar-Rebai E, Belguith N, Fakhfakh F. First functional analysis of a novel splicing mutation in the B3GALTL gene by an ex vivo approach in Tunisian patients with typical Peters plus syndrome. Gene. 2013 Aug 14. [Epub ahead of print]. PubMed ID: 23954224
Novel B3GALTL mutations in classic Peters Plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes Weh E, Reis LM, Tyler RC, Bick D, Rhead WJ, Wallace S, McGregor TL, Dills SK, Chao MC, Murray JC, Semina EV. Novel B3GALTL mutations in classic Peters Plus syndrome and lack of mutations in a large cohort of patients with similar phenotypes. Clin Genet. 2013 Jul 24. [Epub ahead of print]. PubMed ID: 23889335
Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase Lesnik Oberstein SA, Kriek M, White SJ, Kalf ME, Szuhai K, den Dunnen JT, Breuning MH, Hennekam RC. Peters Plus syndrome is caused by mutations in B3GALTL, a putative glycosyltransferase. Am J Hum Genet. 2006 Sep;79(3):562-6. Erratum in: Am J Hum Genet. 2006 Nov;79(5):985. PubMed ID: 16909395
The Peters' plus syndrome: a review Maillette de Buy Wenniger-Prick LJ, Hennekam RC. The Peters' plus syndrome: a review. Ann Genet. 2002 Apr-Jun;45(2):97-103. Review. PubMed ID: 12119218
Peters' anomaly and associated congenital malformations Traboulsi EI, Maumenee IH. Peters' anomaly and associated congenital malformations. Arch Ophthalmol. 1992 Dec;110(12):1739-42. PubMed ID: 1463415
Alagille Syndrome Clinical CharacteristicsOcular Features: The ocular findings in Alagille syndrome are often of little functional significance but can be sufficient to suggest the diagnosis without further study of the systemic features. Posterior embryotoxon is found in 95% of individuals while iris abnormalities such as ectopic pupils are seen in 45%, abnormal fundus pigmentation is common (hypopigmentation in 57%, diffuse pigment speckling in 33%), and optic disc anomalies have been reported in 76%. One study found that 90% of individuals have optic disk drusen by ultrasonography. The anterior chamber anomalies are considered by some to be characteristic of Axenfeld anomaly. The presence of these ocular findings in children with cholestasis should suggest Alagille syndrome. Ocular examination of the parents can also be helpful in this autosomal dominant disorder as some of the same changes are present in one parent in more than a third of cases. Systemic Features: A variety of systemic features, some of them serious malformations, occur in Alagille syndrome. Among the most common is a partial intrahepatic biliary atresia leading to cholestasis and jaundice. Skeletal malformations include 'butterfly' vertebrae, shortened digits, short stature, a broad forehead, and a pointed chin. The tip of the nose may appear bulbous. These features have suggested to some that there is a characteristic facial dysmorphology. Vascular malformations are common including aneurysms affecting major vessels, valvular insufficiency, coarctation of the aorta, and stenosis and these are often responsible for the most serious health problems. In fact, vascular events have been reported to be responsible for mortality in 34% of one cohort. Chronic renal insufficiency develops in a minority of patients. This disorder should always be considered in children with cholestasis, especially when accompanied by cystic kidney disease. Brain MRIs may show diffuse or focal hyperintensity of white matter even in the absence of hepatic encephalopathy. GeneticsThis is an autosomal dominant condition secondary to various mutations in the JAG1 gene located on chromosome 20 (20p12). Penetrance is nearly 100% but there is considerable variation in expression. A far less common variant of this disorder, ALGS2 (610205), is caused by a mutation in the NOTCH2 gene (1p13-p11). Pedigree: Autosomal dominantTreatmentTreatment Options: No cure is available but individual organ disease may be treatable. The ocular abnormalities generally do not cause vision difficulties. Reversible of white matter changes has been noted in a single child following liver transplantation. ReferencesArticle Title: Alagille Syndrome: An Overview Jesina D. Alagille Syndrome: An Overview. Neonatal Netw. 2017 Nov 1;36(6):343-347. PubMed ID: 29185945 Anterior Chamber Pathology in Alagille Syndrome Ho DK, Levin AV, Anninger WV, Piccoli DA, Eagle RC Jr. Anterior Chamber Pathology in Alagille Syndrome. Ocul Oncol Pathol. 2016 Oct;2(4):270-275. PubMed ID: 27843908 CT-defined phenotype of pulmonary artery Rodriguez RM, Feinstein JA, Chan FP. CT-defined phenotype of pulmonary arterystenoses in Alagille syndrome. Pediatr Radiol. 2016 Apr 4. [Epub ahead of print]. PubMed ID: 27041277 Reversible diffuse white matter lesion in Alagille syndrome Takenouchi T, Shimozato S, Kosaki K, Momoshima S, Takahashi T. Reversible diffuse white matter lesion in Alagille syndrome. Pediatr Neurol. 2011 Jul;45(1):54-6. PubMed ID: 21723462 Alagille syndrome: clinical and ocular pathognomonic features El-Koofy NM, El-Mahdy R, Fahmy ME, El-Hennawy A, Farag MY, El-Karaksy HM. Alagille syndrome: clinical and ocular pathognomonic features. Eur J Ophthalmol. 2010 Jul 28. pii: 192165A5-8631-4C06-9C47-9AD63688B02A. [Epub ahead of print] PubMed ID: 20677167 Medical management of Alagille syndrome Kamath BM, Loomes KM, Piccoli DA. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010 Jun;50(6):580-6. PubMed ID: 20479679 Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, Krantz ID. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004 Mar 23;109(11):1354-8. PubMed ID: 14993126 Ocular abnormalities in Alagille syndrome Hingorani M, Nischal KK, Davies A, Bentley C, Vivian A, Baker AJ, Mieli-Vergani G, Bird AC, Aclimandos WA. Ocular abnormalities in Alagille syndrome. Ophthalmology. 1999 Feb;106(2):330-7. PubMed ID: 9951486 Read more about Alagille Syndrome
Alagille Syndrome: An Overview Jesina D. Alagille Syndrome: An Overview. Neonatal Netw. 2017 Nov 1;36(6):343-347. PubMed ID: 29185945
Anterior Chamber Pathology in Alagille Syndrome Ho DK, Levin AV, Anninger WV, Piccoli DA, Eagle RC Jr. Anterior Chamber Pathology in Alagille Syndrome. Ocul Oncol Pathol. 2016 Oct;2(4):270-275. PubMed ID: 27843908
CT-defined phenotype of pulmonary artery Rodriguez RM, Feinstein JA, Chan FP. CT-defined phenotype of pulmonary arterystenoses in Alagille syndrome. Pediatr Radiol. 2016 Apr 4. [Epub ahead of print]. PubMed ID: 27041277
Reversible diffuse white matter lesion in Alagille syndrome Takenouchi T, Shimozato S, Kosaki K, Momoshima S, Takahashi T. Reversible diffuse white matter lesion in Alagille syndrome. Pediatr Neurol. 2011 Jul;45(1):54-6. PubMed ID: 21723462
Alagille syndrome: clinical and ocular pathognomonic features El-Koofy NM, El-Mahdy R, Fahmy ME, El-Hennawy A, Farag MY, El-Karaksy HM. Alagille syndrome: clinical and ocular pathognomonic features. Eur J Ophthalmol. 2010 Jul 28. pii: 192165A5-8631-4C06-9C47-9AD63688B02A. [Epub ahead of print] PubMed ID: 20677167
Medical management of Alagille syndrome Kamath BM, Loomes KM, Piccoli DA. Medical management of Alagille syndrome. J Pediatr Gastroenterol Nutr. 2010 Jun;50(6):580-6. PubMed ID: 20479679
Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality Kamath BM, Spinner NB, Emerick KM, Chudley AE, Booth C, Piccoli DA, Krantz ID. Vascular anomalies in Alagille syndrome: a significant cause of morbidity and mortality. Circulation. 2004 Mar 23;109(11):1354-8. PubMed ID: 14993126
Ocular abnormalities in Alagille syndrome Hingorani M, Nischal KK, Davies A, Bentley C, Vivian A, Baker AJ, Mieli-Vergani G, Bird AC, Aclimandos WA. Ocular abnormalities in Alagille syndrome. Ophthalmology. 1999 Feb;106(2):330-7. PubMed ID: 9951486
