Family Genetic Testing Research Articles

Doenças raras: o que o pediatra necessita saber

Rare disease or an orphan disease is a disease that affects a small percentage of the population. Most of these diseases are present throughout the patients life, even if the symptoms do not appear immediately. They are often fatal or chronically debilitating and the impact on the quality of life of patients and their families is significant. Patients with rare diseases often experience delays in diagnosis, which can negatively impact management and delay treatment. Familial genetic testing or cascade genotyping of all newly diagnosed individuals can speed up the diagnosis of these diseases and allow more patients to be identified at a younger age. Care for patients with chronic and rare diseases is complex, mainly due to lack of knowledge about the disease, which makes accurate and early diagnosis difficult, in addition to the need to perform specific tests, which are sometimes highly complex and costly. Added to these factors are difficulties in obtaining adequate treatment when available, raising awareness of the patient and family about the disease and adherence to treatment. A multidisciplinary approach is very important: care provided by a doctor, nurse, psychologist, nutritionist and social worker. These professionals, in addition to medical care, address the particularities of the disease and treatment, the impact on the life of the patient and his family, the approach to psychological and social issues, and guidance regarding medications and diets.

A novel autism-associated KCNB1 mutation dramatically slows Kv2.1 potassium channel activation, deactivation and inactivation.

KCNB1, on human chromosome 20q13.3, encodes the alpha subunit of the Kv2.1 voltage gated potassium channel. Kv2.1 is ubiquitously expressed throughout the brain and is critical in controlling neuronal excitability, including in the hippocampus and pyramidal neurons. Human KCNB1 mutations are known to cause global development delay or plateauing, epilepsy, and behavioral disorders. Here, we report a sibling pair with developmental delay, absence seizures, autism spectrum disorder, hypotonia, and dysmorphic features. Whole exome sequencing revealed a heterozygous variant of uncertain significance (c. 342 C>A), p. (S114R) in KCNB1, encoding a serine to arginine substitution (S114R) in the N-terminal cytoplasmic region of Kv2.1. The siblings' father demonstrated autistic features and was determined to be an obligate KCNB1 c. 342 C>A carrier based on familial genetic testing results. Functional investigation of Kv2.1-S114R using cellular electrophysiology revealed slowing of channel activation, deactivation, and inactivation, resulting in increased net current after longer membrane depolarizations. To our knowledge, this is the first study of its kind that compares the presentation of siblings each with a KCNB1 disorder. Our study demonstrates that Kv2.1-S114R has profound cellular and phenotypic consequences. Understanding the mechanisms underlying KCNB1-linked disorders aids clinicians in diagnosis and treatment and provides potential therapeutic avenues to pursue.

Perception of genomic newborn screening among peripartum mothers.

Advances in genomic technology have generated possibilities for expanding newborn screening from traditional procedures to genomic newborn screening (gNBS). However, before the implementation of gNBS, it is crucial to address various aspects, including parental attitudes, at the national level. With this aim, we analyzed the attitudes and expectations of Slovenian peripartum mothers regarding gNBS and the acceptability of its implementation into the Slovenian health system. A questionnaire-based study was conducted on a convenience sample of 1136 peripartum mothers (a response rate of 84.1%) in a hospital setting in Slovenia. We measured participants' level of general genetic knowledge, motivation to undergo gNBS, attitude toward its benefits and drawbacks, willingness to participate financially, and factors that would influence their decision to undergo gNBS. Most participants exhibited a positive attitude (83.2%) and were motivated to undertake gNBS (63.4%). They were willing to share genetic data and also contribute to the testing costs. Mothers with better genetic literacy and higher education level, and those with the familial genetic testing experiences were more supportive of gNBS. However, several emotional and socio-ethical concerns were raised regarding how the genetic information would influence family and social life.

Genotype–phenotype correlations in paediatric and adolescent phaeochromocytoma and paraganglioma: a cross-sectional study

Phaeochromocytoma (PC) and paraganglioma (PGL) syndromes associated with germline pathogenic variants are associated with high morbidity and mortality. Establishing genotype–phenotype correlations within a young population is challenging due to their...

Abstract 14479: Compound Heterozygosity With Two Novel Mutations in MYBPC3 as a Cause of Severe and Early-Onset Hypertrophic Cardiomyopathy

Case presentation: A 8-year-old male was diagnosed with severe hypertrophic cardiomyopathy (HCM) after a cardiac arrest from which he was successfully defibrillated. Maximal wall thickness was 23 mm (z-score 6.36) on echocardiography. An implantable cardioverter defibrillator (ICD) was implanted and atenolol was started. After 4 ventricular fibrillation-terminating ICD shocks in the following 2 months, further treatment is under consideration. A genetic test identified the likely pathogenic intronic variant (c.1927+337G>T) in the MYBPC3 gene. An additional variant in the same gene (p.Arg817Gly), of uncertain significance but potentially relevant for the phenotype, was also found. His 10-year-old sister was also diagnosed with severe HCM, genetic test identified the two previously referred variants and ICD was also implanted. In the 4-year-old one sister, who is apparently healthy, only the likely pathogenic intronic variant (c.1927+337G>T) was found. Regarding their parents, both with no evidence of cardiomyopathy, c.1927+337G>T variant was identified in the father, while p.Arg817Gly was present in the mother. Discussion: This clinical case is noteworthy as an example of compound heterozygosity in which each parent donates one alternate allele, being these alleles located at different loci within the same gen, which emphasizes the importance of family genetic testing. The variant of uncertain significance p.Arg817Gly appears to be a disease modifier, causing the phenotype to be expressed early and severely in the presence of the probably pathogenic intronic variant c.1927+337G>T in MYBPC3. This deep intronic variant has not been described previously but was found in thirteen index cases referred for HCM and a history of familial sudden death at an early age, being overrepresented in the cohort of HCM in the north of Spain. Being a carrier of both these two novel variants appears to cause an extremely aggressive childhood-onset phenotype.

Abstract 285: Intraventricular And Subarachnoid Hemorrhage Secondary To Arteriovenous Malformation, A Diagnostic Neurologic Manifestation Of Osler‐Weber‐Rendu Disease

Introduction Osler‐Weber‐Rendu disease, also known as hereditary hemorrhagic telangiectasia (HTT), is a developmental vascular disease characterized by multiple arteriovenous malformations (AVMs) due to genetic defects in endothelial angiogenesis pathways. HHT is a clinical diagnosis based on the fulfillment of the Curacao Diagnostic Criteria, including involvement of internal organs with AVMs, significant recurrent nosebleeds, telangiectasias, and family history of HHT. HHT has a prevalence of 1.5 to 2 people/10,000, although this is considered a falsely low representation due to missed diagnosis and variable penetrance. Autosomal dominantly inherited heterozygous mutations disrupt the TGF‐beta‐mediated pathways causing aberrant blood vessel development with fragility and AVM formation. There are two forms of HHT: (HHT1) has a higher incidence in women and typically involves pulmonary and cerebral arteriovenous malformations (AVM). Mutations in the endoglin gene are thought to be responsible for HTT1 and comprise approximately 61% of the cases. HTT2 is associated with a higher rate of liver AVMs, involves a mutation in Activin A Receptor‐Like Type 1 (ACVRL1), and is responsible for approximately 37% of cases. Other genetic mutations include SMAD4 and GDF2, which are transmitter and binding proteins and occur about 2% of the time. Methods Case report and review of literature Results Case:A 52‐year‐old woman with a large frontoparietal arteriovenous malformation originally found at the age of 17, with a history of frequent epistaxis, mucocutaneous telangiectasias and two children with epistaxis and telangiectasias. Her diagnosis of HHT was made at her third hjospitalization due to a non‐traumatic subarachnoid hemorrhage. A Chest CT angiography and a CT angiography of the intra and extracranial vasculature demonstrated an extensive right holohemispheric cerebral AVM, an unruptured 8‐mm basilar artery aneurysm, and multiple enlarged pulmonary arteries with narrow inlet and outlets concerning for pulmonary AVMs. A subsequent digital subtraction angiogram (DSA) of the brain confirmed the extensive holohemispheric AVM, unruptured basilar artery aneurism with subarachnoid hemorrhage originating from the AVM. On examination she had multiple lingual, and hard/soft palate telangiectasias and an extensive anterior pedal telangiectasia. Given the heavy cerebral AVM burden with multiple cerebral artery feeders, the AVM angiosclerosis and basilar artery aneurysm embolization were deferred. The patient proceeded under medical management alone with a plan for personal and familial genetic testing. Conclusion HHT is a rare cause of cerebral AVMs at high risk of spontaneous bleeding. Managing these AVMs can be a challenge, given the extent and location of these. However, diagnosis of HHT can inform prognosis and guide medical management due to improved prognosis for HHT‐related AVMs and aneurysms compared to non‐HHT AVMs.

RAF1 mutation leading to hypertrophic cardiomyopathy in a Chinese family with a history of sudden cardiac death: A diagnostic insight into Noonan syndrome.

Hypertrophic cardiomyopathy (HCM) is predominantly caused by mutations in sarcomeric genes. However, a subset of cases is attributed to genetic disorders unrelated to sarcomeric genes, such as Noonan syndrome (NS) and other RASopathies. In this study, we present a family with a history of sudden cardiac death (SCD) and focus on two adults with syndromic left ventricular hypertrophy (LVH). Clinical evaluations, including echocardiography, were conducted to assess cardiac manifestations. Whole-exome sequencing was performed to identify potential genetic variants underlying syndromic LVH in the study participants. Whole-exome sequencing revealed a missense variant in the RAF1 gene, c.782C>T (p.Pro261Leu). This variant confirmed the diagnosis of NS in the affected individuals. The findings of this study underscore the importance of family history investigation and genetic testing in diagnosing syndromic LVH. By identifying the underlying genetic cause, clinicians can better understand the etiology of RAS-HCM and its association with SCD in young adults.

More than just mild thrombocytopenia: Clinical clues in the diagnosis of germline predisposition to malignancy from a rare ETV6 variant

Key Clinical MessageIn the evaluation of patients with longstanding mild thrombocytopenia, emphasis on family history, genetic testing, and collaborative clinical and laboratory‐based family studies can ensure proper diagnosis and monitoring for malignancies.AbstractWe report the diagnostic approach to mild and non‐specific thrombocytopenia with unclear genetic findings in two sisters. Genetic sequencing revealed a rare variant in ETS Variant Transcription Factor 6, which is associated with inherited thrombocytopenia with predisposition to hematologic malignancy. Familial studies provided sufficient evidence for a likely pathogenic classification.

Genetic spectrum of familial and sporadic dilated cardiomyopathy: arrhythmic phenotypes associated with mutations in the lamin A/C (LMNA) gene

Purpose. To study the diagnostic value of cascade family screening and the spectrum of genetic variants in patients with familial and sporadic DCM, assess clinical outcomes and comparative analysis of 5-year event-free survival.Materials and methods. The study included 156 unrelated patients with verified DCM. All patients (aged 46 [34; 57] years; 125 (80%) male; LVEF 31 [24; 38]%; LV EDD 68 [61; 74] mm; follow-up period - 77 [59; 108] months) a complex of clinical and instrumental studies (ECG, ECHO, HM, MRI), cascade family screening with genetic testing (NGS+Sanger) and segregation analysis were performed.Results. Criteria for familial DCM were identified in 73 (46.8%) probands. The genetic cause of DCM was identified in 47 (64,4%) familial cases, while for sporadic form DCM pathogenic variants were detected in 19 (22,9%) patients. The dominant mutations were truncating variants in the titin gene (10,9%) and variants in the lamin A/C (LMNA) gene - 8,33%. As a result of the evaluation of cumulative event-free survival (Kaplan-Meier curves), LMNA carriers showed the poor 5-year prognosis for ventricular tachyarrhythmic events (x2=39.9; p=0,0001) and composite adverse outcomes (x2=12.1; p=0.001). Probands who had a familial DCM (log rang x2=38.5; p=0,0001) showed the worst prognosis and low cumulative survival when compared with patients of the sporadic DCM.Conclusion. Cascade clinical family screening and genetic testing in the DCM cohort increased the level of diagnosis of familial DCM from 4.5% to 46.8%. Associations of LMNA mutations with life-threatening tachyarrhythmias are defined as prognostically significant, that confirms the important role of genetic stratification of arrhythmic risk.

Genetic testing and family screening in idiopathic pediatric cardiomyopathy: a prospective observational study from a tertiary care center in North India

IntroductionThere are limited data on family screening and genetic testing in pediatric cardiomyopathy from India. This study was conducted to describe the morphologic spectrum and identify potential familial and genetic causes of pediatric cardiomyopathies in this region.MethodsFrom April 2018 to May 2020, all children from birth to 18 years of age with cardiomyopathy visiting a tertiary care hospital in North India were enrolled in this study. First-degree relatives of index patients were offered screening for cardiomyopathy; 260 clinically reported pathogenic/likely pathogenic variants in 17 genes were analyzed by a rapid genotyping method. Additionally, a subset of patients also underwent whole-exome sequencing.ResultsOf the 20 patients enrolled in this study (median age 42 months), 18 were clinically diagnosed with dilated cardiomyopathy. We observed a 44.4% mortality rate after a median follow-up of 15 months. 61.3% of the eligible first-degree relatives underwent screening, and one patient was identified to have familial cardiomyopathy. Multi-panel gene testing was performed on 18 patients, and none were found to have a pathogenic or likely pathogenic variant; 9 patients also underwent whole-exome sequencing, and pathogenic and likely pathogenic variants were identified in 50% (4/8) of them.ConclusionDilated cardiomyopathy is the most common morphologic form of pediatric cardiomyopathy in India and has a high mortality rate. The prevalence of familial cardiomyopathy was low in this study. Future studies should evaluate the role of whole-exome sequencing in identifying genetic causes of cardiomyopathy in children.

Privacy and utility of genetic testing in families with hereditary cancer syndromes living in three countries: the international cascade genetic screening experience.

Background: Hereditary breast and ovarian cancer and Lynch syndrome are associated with increased lifetime risk for common cancers. Offering cascade genetic testing to cancer-free relatives of individuals with HBOC or LS is a public health intervention for cancer prevention. Yet, little is known about the utility and value of information gained from cascade testing. This paper discusses ELSI encountered during the implementation of cascade testing in three countries with national healthcare systems: Switzerland, Korea, and Israel. Methods: A workshop presented at the 5th International ELSI Congress discussed implementation of cascade testing in the three countries based on exchange of data and experiences from the international CASCADE cohort. Results: Analyses focused on models of accessing genetic services (clinic-based versus population-based screening), and models of initiating cascade testing (patient-mediated dissemination versus provider-mediated dissemination of testing results to relatives). The legal framework of each country, organization of the healthcare system, and socio-cultural norms determined the utility and value of genetic information gained from cascade testing. Conclusion: The juxtaposition of individual versus public health interests generates significant ELSI controversies associated with cascade testing, which compromise access to genetic services and the utility and value of genetic information, despite national healthcare/universal coverage.

Comprehensive management of type A acute aortic dissection in the paediatric population with ACTA 2 mutation: case reports and literature review of paediatric aortic dissection.

Acute aortic dissection in the paediatric population is rare but lethal. We present two paediatric cases of type A acute aortic dissection that required emergent procedures and were later found to have genetic mutations. High index of suspicion, early clinical diagnosis, prompt treatment, the advantageous collaboration between the paediatric team and aortic surgeons, and familial genetic testing are paramount to achieve a good outcome.

TBX1 copy number variant of unknown significance presenting as severe esophageal stricture and recurrent candidiasis

IntroductionTBX1 Is involved in pharyngeal pouch development affecting thymus, parathyroid, craniofacial, and cardiac outflow tract development. TBX1 deletions present with phenotype of Di George syndrome. We present the case of a patient with esophageal stricture and candidiasis showing a novel TBX1 gene triplication VUS. Case descriptionA 27-year-old male was hospitalized for hematemesis and progressive dysphagia. The physical exam was remarkable for short stature, underweight, dental hypoplasia, alopecia and occipital vitiligo. Calcium and lymphocyte numbers were normal. Severe esophageal strictures precluded upper endoscopy. He received IV fluconazole for two weeks to continue oral antifungal indefinitely. Since infancy he has had multiple candida infections in nails and oral mucosa requiring fluconazole, and medical history of asthma and atopic dermatitis. No history of cardiac abnormalities. At 14 years old he started with progressive dysphagia. Barium swallow and endoscopies showed severe acute and chronic esophagitis and thoracic esophageal strictures with severe stenosis. Patient's sister has history of candida infections, hypocalcemia due to hypoparathyroidism, and hypothyroidism. There is consanguinity among paternal grandparents. Invitae PID panel showed VUS with TBX1 gene triplication, not previously reported. Familial genetic testing was requested for her sister to support the diagnosis of DiGeorge Syndrome. DiscussionTBX1 gene deletions present a spectrum clinical phenotype including thymic hypoplasia, hypocalcemia, and congenital heart defects. TBX1 duplication and gain of function TBX1 heterozygous mutation led to protein dysfunction and a similar phenotype caused by loss-of-function mutations or deletions. TBX1 triplication could plausibly lead to dysfunctional protein expression, which requires confirmation. TBX1 is a negative regulator of thymic epithelial cell differentiation and proliferation, which could affect immune regulation and explain patient's chronic candida infections. Feeding difficulties and esophageal dysmotility have been reported in Di George syndrome. Sibling's hypocalcemia due to hypoparathyroidism could be explained by TBX1 dysfunction. APECED was considered in differential diagnosis due to chronic mucocutaneous candidiasis and sister's endocrinopathies, nevertheless, no AIRE or STAT1 mutations identified. Genetic analysis and familiar VUS have the potential to identify the cause of PIDs. TBX1 transcript and protein expression analysis will contribute to confirming the diagnostic impression.

Cascade Genetic Risk Education and Testing in Families With Hereditary Cancer Syndromes: A Pilot Study.

Cascade genetic risk evaluation in families with hereditary cancer can reduce the burden of disease but the rate of germline genetic testing in relatives of patients at risk is low. We identified all 277 women diagnosed with breast cancer in Georgia in 2017 who linked to a clinically actionable germline pathogenic variant through a Surveillance, Epidemiology, and End Results registry-variant linkage initiative. We surveyed them, and then invited eligible respondents to an online platform hosted by a navigator that offered cancer genetic risk education and germline genetic testing to untested relatives. We randomly assigned patient-family clusters at the time of the patient enrollment offer to free versus $50 (USD) test cost. Patients invited relatives to join the study through personalized e-mail. Enrolled relatives received online cancer genetic education and the opportunity to order clinical germline genetic testing through the platform. The primary outcome was the number of relatives who ordered genetic testing. One hundred twenty-five of 277 patients completed surveys (45.2%). Most respondents were eligible for the trial offer (113 of 125; 90.4%). In the free testing arm, 20 of 56 eligible patients participated (35.7% of eligible respondents) and they invited 28 relatives: 12 relatives enrolled and 10 ordered testing. In the $50 (USD) arm, 16 of 57 eligible patients participated (28.1%) and they invited 38 relatives: 18 relatives enrolled and 17 ordered testing. Cascade genetic testing in families with hereditary cancer syndromes accrued through a population-based cancer registry can be achieved through an online platform that offers genetic risk education and low-cost testing to relatives. A modest charge did not appear to influence the percentage of participating patients, numbers of participating relatives, and numbers of relatives who received genetic testing.

Clinical Evaluation of Patients with Genetically Confirmed Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is the most common genetic disorder associated with premature atherosclerotic cardiovascular (CV) disease (ASCVD). However, it still is severely underdiagnosed. Initiating lipid-lowering therapy (LLT) in FH patients early in life can substantially reduce their ASCVD risk. As a result, identifying FH is of the utmost importance. The increasing availability of genetic testing may be useful in this regard. We aimed to evaluate the genetic profiles, clinical characteristics, and gender differences between the first consecutive patients referred for genetic testing with FH clinical suspicion in our institution (a Spanish cohort). Clinical information was reviewed, and all participants were sequenced for the main known genes related to FH: LDLR, APOB, PCSK9 (heterozygous FH), LDLRAP1 (autosomal recessive FH), and two other genes related to hyperlipidaemia (APOE and LIPA). The genetic yield was 32%. Their highest recorded LDLc levels were 294 ± 65 SD mg. However, most patients (79%) were under > 1 LLT medication, and their last mean LDLc levels were 135 ± 51 SD. LDLR c.2389+4A>G was one of the most frequent pathogenic/likely pathogenic variants and its carriers had significantly worse LDLc highest recorded levels (348 ± 61 SD vs. 282 ± 60 SD mg/dL, p = 0.002). Moreover, we identified an homozygous carrier of the pathogenic variant LDLRAP1 c.207delC (autosomal recessive FH). Both clinical and genetic hypercholesterolemia diagnosis was significantly established earlier in men than in women (25 years old ± 15 SD vs. 35 years old ± 19 SD, p = 0.02; and 43 ± 17 SD vs. 54 ± 19 SD, p = 0.02, respectively). Other important CV risk factors were found in 44% of the cohort. The prevalence of family history of premature ASCVD was high, whereas personal history was exceptional. Our finding reaffirms the importance of early detection of FH to initiate primary prevention strategies from a young age. Genetic testing can be very useful. As it enables familial cascade genetic testing, early prevention strategies can be extended to all available relatives at concealed high CV risk.

Parental mosaicism detection and preimplantation genetic testing in families with multiple transmissions of de novo mutations

BackgroundDe novo mutations (DNMs) are linked with many severe early-onset disorders ranging from rare congenital malformation to intellectual disability. Conventionally, DNMs are considered to have an estimated recurrence rate of...

O15: Cancer genetic testing in families across Utah: Development of a statewide database*

O15: Cancer genetic testing in families across Utah: Development of a statewide database*

DOENÇAS RARAS: O QUE O PEDIATRA NECESSITA SABER

Rare disease or an orphan disease is a disease that affects a small percentage of the population. Most of these diseases are present throughout the patients life, even if the symptoms do not appear immediately. They are often fatal or chronically debilitating and the impact on the quality of life of patients and their families is significant. Patients with rare diseases often experience delays in diagnosis, which can negatively impact management and delay treatment. Familial genetic testing or cascade genotyping of all newly diagnosed individuals can speed up the diagnosis of these diseases and allow more patients to be identified at a younger age. Care for patients with chronic and rare diseases is complex, mainly due to lack of knowledge about the disease, which makes accurate and early diagnosis difficult, in addition to the need to perform specific tests, which are sometimes highly complex and costly. Added to these factors are difficulties in obtaining adequate treatment when available, raising awareness of the patient and family about the disease and adherence to treatment. Residência Pediátrica; 2023: Ahead of Print. DOI: 10.25060/residpediatr-2023-1062 Nota aos leitores: pode haver informações pendentes, por se tratar de um artigo em “visualização pré-publicação”. A multidisciplinary approach is very important: care provided by a doctor, nurse, psychologist, nutritionist and social worker. These professionals, in addition to medical care, address the particularities of the disease and treatment, the impact on the life of the patient and his family, the approach to psychological and social issues, and guidance regarding medications and diets.

Progressive pseudorheumatoid dysplasia in an Omani family: a case report

Background: Progressive pseudorheumatoid dysplasia (PPRD) is an inherited autosomal recessive musculoskeletal condition caused by mutations in the Cellular Communication Network Factor 6 (CCN6) gene. This causes a variety of clinical features such as short stature, genu varum, etc. Case Presentation: This study reported cases of three patients from the same family who exhibited the clinical features of PPRD, and the condition was diagnosed through confirmatory genetic testing. The whole exome sequencing test results for the 15-year-old and 3-year-old males revealed a class-5 pathogenic homozygous mutation in the CCN6 gene, resulting in both individuals being diagnosed with autosomal recessive PPRD. The results for the third patient had not come out yet. Conclusion: For patients with PPRD, it is necessary to take the full family history and genetic testing that might help in the diagnosis and treatment of the condition.

266 Breast Cancer in Women Under 30: A Multidisciplinary Approach in a Unique Cohort

Abstract Aim Breast cancer in younger women is relatively rare, tends to be more aggressive and is associated with unique challenges. We sought to examine our practice in managing cancer in patients under 30. Method A retrospective case-note review was performed on patients under 30 years of age diagnosed with invasive breast through our pathology database since 2007. Clinical and pathological data was collected on patients’ cancers, management and follow up as well family history, genetic testing, and fertility management. Results Forty-five patients were identified. Median age was 28 years (range 20 to 30). Mean tumour size was 30mm (range 4–65mm). Seventeen (38%) of cancers were ER negative, 16 (36%) were HER2 positive. Twenty-three patients (51%) had positive lymph node metastases. SIx patients (13%) had a strong family history and 9 (20%) were BRCA 1 or 2 gene positive. Seven patients (15%) underwent contra-lateral risk-reducing mastectomy. Twenty-5 patients (55%) had no children at diagnosis. Fertility management was discussed with >90% of patients and 12 patients (26%) underwent ovum or embryo preservation. Over a median follow up of 40.5 months (range 4.5 to 128 months), 8 patients (18%) developed local or distant recurrence and 6 patients (13%) died (due to metastasis). Conclusion In our experience, breast cancer patients under 30 had more aggressive cancers with a relatively high rate of axillary metastases at presentation. Young patients with breast cancer face unique management challenges such as fertility, genetic testing and survivorship issues that are best addressed in a multidisciplinary setting.