cardiac defects

Schurrs-Hoeijmakers Syndrome

Clinical Characteristics
Ocular Features: 

Mild structural variants are common among the periocular structures.  There is marked hypertelorism in many individuals, the eyebrows are full and highly arched, the eyelashes are long, and the lid fissures slant downward.  Ptosis is often evident.  Myopia, nystagmus, and strabismus are frequently noted.  Colobomas have been reported.

Systemic Features: 

There is general psychomotor delay in development.  Intellectual disability (with IQs in the 50s) and hypotonia are common.  Speech is poor and sometimes absent.   Behavioral anomalies such as aggression and features of autism have been reported.  The anterior hairline is low, the mouth is wide with downturned corners, the nose is bulbous, the ears are large and low-set, and the teeth are often widely-spaced.  Cryptorchidism is common among males.

Renal and cardiac defects are common.  Brain MRIs often show cerebellar hypoplasia, enlarged ventricles, and nonspecific white matter changes.

Genetics

No treatment for the general disorder has been published.  Physical and speech therapy might be helpful

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

No treatment for the general disorder has been published.  Physical and speech therapy might be helpful.

References
Article Title: 

Clinical delineation of the PACS1-related syndrome--Report on 19 patients

Schuurs-Hoeijmakers JH, Landsverk ML, Foulds N, Kukolich MK, Gavrilova RH, Greville-Heygate S, Hanson-Kahn A, Bernstein JA, Glass J, Chitayat D, Burrow TA, Husami A, Collins K, Wusik K, van der Aa N, Kooy F, Brown KT, Gadzicki D, Kini U, Alvarez S, Fernandez-Jaen A, McGehee F, Selby K, Tarailo-Graovac M, Van Allen M, van Karnebeek CD, Stavropoulos DJ, Marshall CR, Merico D, Gregor A, Zweier C, Hopkin RJ, Chu YW, Chung BH, de Vries BB, Devriendt K, Hurles ME, Brunner HG; DDD study. Clinical delineation of the PACS1-related syndrome--Report on 19 patients. Am J Med Genet A. 2016 Mar;170(3):670-5.

PubMed ID: 
26842493

Spondyloocular Syndrome

Clinical Characteristics
Ocular Features: 

Cataracts have been noted in several patients in the first and second decades of life.  Nystagmus and ‘amblyopia’ have also been reported.  Several individuals have had retinal detachments.

Systemic Features: 

Only a small number of families have been reported.  Poor bone mineralization with frequent fractures in long bones and vertebral compression seem to be consistent features often noted in the first and second decades of life.  Moderate osteoporosis and advanced bone age with platyspondyly may be present.  The vertebral fractures lead to abnormal spinal curvature and may result in shortened stature. 

Some sensorineural hearing loss is sometimes detected in the first decade.  The ears have been described as low-set and posteriorly rotated.  A variety of cardiac defects have been reported including mitral valve prolapse, septal defects, and anomalies of the aortic valve. 

Genetics

This is an autosomal recessive disorder secondary to homozygous mutations in the XYLT2 gene located at 17q21.33. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Pamidronate given intravenously seems to have little therapeutic value.  Hearing aids can be beneficial.  Lensectomy may be of benefit although no reports of cataract surgery have been reported.  Fractures need immediate attention.  Patient may become wheelchair-bound by the second decade.  Special education may be helpful for those with learning difficulties.

References
Article Title: 

Oculootofacial Dysplasia

Clinical Characteristics
Ocular Features: 

Many patients have lower lid colobomas, sometimes with malformations of the zygoma.  The palpebral fissures may appear narrow while some patients have a suggestion of hypertelorism.

Systemic Features: 

Neural development is normal but patients have significant facial dysmorphism. A variety of organ and bony malformations have been described.  Cardiac septal defects and sometimes renal malformations may be present.  The ears are large and are sometimes associated with preauricular tags.  Cleft lip and/or palate with bifid uvula, micrognathia, high nasal bridge, large nose, a short philtrum, choanal atresia, and mixed hearing loss are often present.  Choanal atresia is common.

Genetics

Biallelic loss-of-function mutations in the TXNL4A gene have been found in this presumed autosomal recessive condition. 

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

Individual malformations can often be surgically corrected.

References
Article Title: 

Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome

Wieczorek D, Newman WG, Wieland T, Berulava T, Kaffe M, Falkenstein D, Beetz C, Graf E, Schwarzmayr T, Douzgou S, Clayton-Smith J, Daly SB, Williams SG, Bhaskar SS, Urquhart JE, Anderson B, O'Sullivan J, Boute O, Gundlach J, Czeschik JC, van Essen AJ, Hazan F, Park S, Hing A, Kuechler A, Lohmann DR, Ludwig KU, Mangold E, Steenpass L, Zeschnigk M, Lemke JR, Lourenco CM, Hehr U, Prott EC, Waldenberger M, Bohmer AC, Horsthemke B, O'Keefe RT, Meitinger T, Burn J, Ludecke HJ, Strom TM. Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome. Am J Hum Genet. 2014 Dec 4;95(6):698-707.

PubMed ID: 
25434003

Temtamy Syndrome

Clinical Characteristics
Ocular Features: 

Bilateral chorioretinal colobomas may be present and involve the optic nerve in one-third of patients.  Visual acuity is not measureable but significant vision impairment is evident in most patients and may be progressive in some individuals.  Several have been reported with dislocated lenses, ptosis, microcornea, cataracts, microphthalmia, myopia, and posterior staphylomas.

Systemic Features: 

Mild, nonspecific craniofacial dysmorphism is often present.  Some form of macrocephaly, with an elongated face, low-set ears, and micrognathia has been reported.  Short stature is of the proportionate type.  Significant developmental delay is evident during childhood and patients are nonverbal. A variety of cardiovascular anomalies such as septal defects, aortic dilation, and patent ductus arteriosus have been described. MRI shows mild hypoplasia of the corpus callosum.   The gait may be ataxic and some (59%) individuals have spasticity of limb muscles with or without contractures.  Seizures develop in early childhood, usually before the age of 3 years, and are difficult to control. 

Genetics

The inconsistent and highly variable phenotype hints that this is a genetically heterogeneous condition.  Many patients seem to have an autosomal recessive condition secondary to mutations in C12orf57 (12p13.31).

A syndrome consisting primarily of colobomas, ptosis, hypertelorism, and global delay (243310) has some similar clinical features but is caused by mutations in ACTG1.

Treatment
Treatment Options: 

No therapy is available for the syndrome but attempts to control the seizures should be made. 

References
Article Title: 

Exome sequencing identifies compound heterozygous mutations in C12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures

Platzer K, Huning I, Obieglo C, Schwarzmayr T, Gabriel R, Strom TM, Gillessen-Kaesbach G, Kaiser FJ. Exome sequencing identifies compound heterozygous mutations in C12orf57 in two siblings with severe intellectual disability, hypoplasia of the corpus callosum, chorioretinal coloboma, and intractable seizures. Am J Med Genet A. 2014 May 5. [Epub ahead of print].

PubMed ID: 
24798461

Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia

Akizu N, Shembesh NM, Ben-Omran T, Bastaki L, Al-Tawari A, Zaki MS, Koul R, Spencer E, Rosti RO, Scott E, Nickerson E, Gabriel S, da Gente G, Li J, Deardorff MA, Conlin LK, Horton MA, Zackai EH, Sherr EH, Gleeson JG. Whole-exome sequencing identifies mutated c12orf57 in recessive corpus callosum hypoplasia. Am J Hum Genet. 2013 Mar 7;92(3):392-400.

PubMed ID: 
23453666

New autosomal recessive multiple congenital abnormalities/mental retardation syndrome with craniofacial dysmorphism absent corpus callosum, iris colobomas and connective tissue dysplasia

Temtamy SA, Salam MA, Aboul-Ezz EH, Hussein HA, Helmy SA, Shalash BA. New autosomal recessive multiple congenital abnormalities/mental retardation syndrome with craniofacial dysmorphism absent corpus callosum, iris colobomas and connective tissue dysplasia. Clin Dysmorphol. 1996 Jul;5(3):231-40. Review.

PubMed ID: 
8818452

Microphthalmia, Syndromic 8

Clinical Characteristics
Ocular Features: 

Microphthalmia is a consistent feature and short palpebral fissures have been described in one patient.  Microcornea has also been noted.  At least one patient was blind.

Systemic Features: 

The skull is small and mental retardation is usually a feature.  Other variable abnormalities include cardiac defects, prognathism, split-feet, cryptorchidism, and cleft lip and palate.  Few patients have been reported and the full phenotype is unknown.

Genetics

The gene remains unidentified in this rare syndrome but a locus has been identified at 6p21.  In at least one patient with a balanced translocation of t(6;13)(q21;q12) a disruption in the SNX3 gene at 6q21 was identified.  Most cases occur sporadically and have cytogenetic abnormalities.

Treatment
Treatment Options: 

No treatment is known.

References
Article Title: 
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