Cutis marmorata telangiectatica congenita: a focus on its diagnosis, ophthalmic anomalies, and possible etiologic factors.

Purpose: Cutis marmorata telangiectatica congenita (CMTC) is a rare congenital disorder typified by localized or generalized cutaneous vascular anomalies, which dissipate over time. We review the diagnostic approach to CMTC and present a comprehensive examination of its ocular manifestations. Additionally, we offer recommendations for the ophthalmologic workup for patients with CMTC. Finally, we examine the possible causes of CMTC and summarize the current efforts to establish an etiologic mechanism for this disease.Methods: Thirty-three published cases of CMTC with ocular anomalies are examined in detail.Results: CMTC is diagnosed based on a specific set of congenital cutaneous symptoms, principally congenital reticular erythema that is unresponsive to local warming and absence of venectasia within the skin lesions. Ocular findings are not currently employed in this diagnostic process, likely due to an incomplete understanding into their presentation, frequency, and natural history. We show that the majority of ophthalmic manifestations are congenital, with glaucoma and posterior segment anomalies, consisting of retinal perfusion defects and vascular abnormalities, as the most frequently reported findings. Typical ophthalmic medical and surgical interventions appear to be effective for management of these CMTC-related pathology. Unfortunately, the etiology and pathophysiology of CMTC remains unknown, which obfuscates efforts to identify, examine, and initiate treatment in patients.Conclusions: While the ophthalmic community has traditionally viewed glaucoma as the classic ocular anomaly of CMTC, this dataset advocates for the prompt investigation of posterior segment abnormalities as well. However, our understanding of CMTC's ocular anomalies is complicated by a lack of reporting and/or incomplete (or nonexistent) ophthalmic examinations, and we strongly encourage comprehensive ophthalmic examinations for all CMTC patients at the time of diagnosis, followed by appropriate screening and surveillance throughout life. We believe these recommendations will spur additional data and disease insights that may be useful for future refinements to CMTC diagnostic algorithms.

Genetics of syndromic and nonsyndromic aortopathies.

PURPOSE OF REVIEW: To review the literature and provide a summary of management of syndromic and nonsyndromic aortopathies. RECENT FINDINGS: The number of newly identified genetic causes for aortopathies have continued to increase over the past 10 years. The number of reported individuals with most hereditary aneurysm genes is small but increasing with more publications focusing describing the natural history caused by each gene. SUMMARY: Aortopathy can present as an isolated finding or present as part of a larger genetic syndrome. Advances in genetic testing technology has shed light on the increasing importance of molecular diagnostics in the evaluation and management of patients with hereditary aortic disease. Molecular diagnostics and family phenotyping can aide in the diagnosis and management of pediatric patients with aortic disease.

Evolving Approaches to Genetic Evaluation of Specific Cardiomyopathies.

The understanding of the genetic basis of cardiomyopathy has expanded significantly over the past 2 decades. The increasing availability, shortening diagnostic time, and lowering costs of genetic testing have provided researchers and physicians with the opportunity to identify the underlying genetic determinants for thousands of genetic disorders, including inherited cardiomyopathies, in effort to improve patient morbidities and mortality. As such, genetic testing has advanced from basic scientific research to clinical application and has been incorporated as part of patient evaluations for suspected inherited cardiomyopathies. Genetic evaluation framework of inherited cardiomyopathies typically encompasses careful evaluation of family history, genetic counseling, clinical screening of family members, and if appropriate, molecular genetic testing. This review summarizes the genetics, current guideline recommendations, and evidence supporting the genetic evaluation framework of five hereditary forms of cardiomyopathy: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), restrictive cardiomyopathy (RCM), and left ventricular noncompaction (LVNC).

Midterm results of David reimplantation in patients with connective tissue disorder.

BACKGROUND: Few series have examined follow-up risks of the David reimplantation operation in patients with connective tissue disorder. Hence, we assessed its midterm safety and effectiveness for Marfan syndrome and other connective tissue disorders, such as Ehlers-Danlos, Loeys-Dietz, and marfanoid syndromes. METHODS: Of 313 patients who underwent modified David reimplantation, 178 identified as having connective tissue disorders underwent operation from January 1, 1991, to December 31, 2010. These disorders included Marfan (84%), marfanoid (8.4%), Loeys-Dietz (5.6%), Ehlers-Danlos (1.1%), and other syndromes (1.1%). Concomitant procedures included mitral valve repair in 7.3% and an atrial fibrillation procedure in 3.4%. RESULTS: There were no operative or 30-day deaths. Complications included prolonged ventilation (3%), renal failure (3%), reoperation for bleeding (2.2%), and permanent stroke (0.56%). Eight-year survival was 94% and freedom from aortic valve reoperation at 6 years was 92%. Of the 7 aortic valve reoperations, 3 were attributable to endocarditis and 3 to technical failure. One reoperation was performed at another hospital, and the reason could not be determined. There were no late strokes or hemorrhagic events. At 4 years, approximately 70% of patients had no aortic valve regurgitation, and 18% were in grade 1+. CONCLUSIONS: Prophylactic root and valve preservation using David reimplantation is safe and provides excellent midterm effectiveness and low risk of late events except for endocarditis.

Genetic counselors: your partners in clinical practice.

As our understanding of the human genome has grown, so too has the need for health care providers who can help patients and families understand the implications of these new discoveries for their health care. Increasingly, genetic counselors are working in partnership with physicians to provide a continuum of care from risk assessment to diagnosis. In this article, we explain the process of genetic counseling and its value for patients who have a personal or family history of a hereditary condition.

Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25.

Reports of individuals with deletions of 1q24→q25 share common features of prenatal onset growth deficiency, microcephaly, small hands and feet, dysmorphic face and severe cognitive deficits. We report nine individuals with 1q24q25 deletions, who show distinctive features of a clinically recognizable 1q24q25 microdeletion syndrome: prenatal-onset microcephaly and proportionate growth deficiency, severe cognitive disability, small hands and feet with distinctive brachydactyly, single transverse palmar flexion creases, fifth finger clinodactyly and distinctive facial features: upper eyelid fullness, small ears, short nose with bulbous nasal tip, tented upper lip, and micrognathia. Radiographs demonstrate disharmonic osseous maturation with markedly delayed bone age. Occasional features include cleft lip and/or palate, cryptorchidism, brain and spinal cord defects, and seizures. Using oligonucleotide-based array comparative genomic hybridization, we defined the critical deletion region as 1.9 Mb at 1q24.3q25.1 (chr1: 170,135,865-172,099,327, hg18 coordinates), containing 13 genes and including CENPL, which encodes centromeric protein L, a protein essential for proper kinetochore function and mitotic progression. The growth deficiency in this syndrome is similar to what is seen in other types of primordial short stature with microcephaly, such as Majewski osteodysplastic primordial dwarfism, type II (MOPD2) and Seckel syndrome, which result from loss-of-function mutations in genes coding for centrosomal proteins. DNM3 is also in the deleted region and expressed in the brain, where it participates in the Shank-Homer complex and increases synaptic strength. Therefore, DNM3 is a candidate for the cognitive disability, and CENPL is a candidate for growth deficiency in this 1q24q25 microdeletion syndrome.