Delayed Diagnosis of McCune–Albright Syndrome

Background. McCune–Albright syndrome (MAS) is a rare heterogeneous genetic disorder that is characterized by a triad of polyostotic fibrous dysplasia (FD), café au lait spots (CAL), and multiple hyperfunctional endocrinopathies. In general, it is diagnosed clinically. From the triads, two of the findings are enough to make the diagnosis, but genetic testing can be done if it is available. Case Presentation. We report a female child who was symptomatic since the neonatal period with skin hyperpigmentation, breast enlargement, and vaginal bleeding. She was diagnosed with MAS at the age of five years. She had pathological fractures at multiple sites and had raised thyroid hormones since the age of 3½ years. The child developed severe morbidity as the result of delayed diagnosis and currently became wheelchair dependent. Conclusion. Thorough patient evaluation and appropriate interpretation of findings are crucial steps for timely diagnosis of MAS and better patient care outcomes.

Abstract 17116: Recurrent Atrial Myxomas As A Presenting Feature Of Carney Complex

Case Presentation: A 24-year-old man with a history of adrenal insufficiency on hydrocortisone presented to the hospital after losing consciousness in a swimming pool and was found to have an acute MCA stroke. PMHx was significant for left atrial myxoma status post resection 3 years ago, known L frontal brain, L adrenal, and testicular masses status post-resection. His father had a history of resected left atrial mass. Cardiology was consulted for a L atrial mass on the bedside echocardiogram upon initial emergency evaluation, during which the patient was placed on mechanical ventilation with stable vitals. The cardiovascular exam revealed a midsternal scar but was otherwise normal. Pulses were 2+ bilaterally on the upper and lower extremities. The skin was noted to have multiple hyperpigmented macules resembling cafe-au lait spots. The patient underwent mechanical thrombectomy with thrombolysis for his large MCA occlusion. His postoperative course was complicated by a worsening neuro exam in the setting of mid-line shift for which he had undergone decompressive hemicraniectomy. His adrenal insufficiency was managed by endocrinology. A TTE was significant for a L atrial mass measuring 4.8 cm attached to the interatrial septum with a stalk. A CT scan identified 2 discrete hypodensities of 8 mm and 3.8 cm which were thought to be the cardioembolic source for the stroke. An abdominal CT revealed a recurrent L adrenal neoplasm with absent R adrenal gland post resection of neoplasm. Conservative cardiac management was elected in the setting of a worsening neuroprognosis with follow-up post neurologic insult. Discussion: Considering the constellation of neoplastic and cutaneous findings, this was diagnosed as a case of Carney complex. This case identifies recurrent myxoma as a unique feature of Carney complex, ruling out other differentials such as neurofibromatosis and MEN syndrome. It highlights the importance of screening to prevent embolic stroke from recurrent myxomas.

Prevention of pathological fracture in fibrous dysplasia of proximal femur in a 24-year-old female a rare presentation - a case report

<p class="abstract">Fibrous dysplasia (FD) was historically mentioned in the medical literature in 1938 by Dr. Lichtenstein and in 1942 by Dr. Lichtenstein and Jaffe. The term Jaffe-Lichtenstein syndrome is sometimes used synonymously with monostotic FD or to denote cases of polyostotic FD with café au lait spots, but no endocrine dysfunction. Our case is a 24-year-old female, housewife presented to our hospital with a complaints of right hip pain and backache with difficulty in walking of 6 months duration. She had dull aching pain which increased in intensity with the course of time, there was no radiation, but was aggravated by movements. She was managed with dynamic hip screw along with curettage of the lesion and bone graft, after 9 months of follow up, she had no pain over her hip and there was calcification over the previous lesion, our patient had a very favourable outcome.</p>

Kosaki Overgrowth Syndrome: Report of a Family with a Novel PDGFRB Variant

Heterozygous activating missense variants of <i>PDGFRB</i> are associated with the phenotype of Kosaki overgrowth syndrome (KOGS). Here, we present a family including a father and 2 siblings with a novel variant, c.2567A&#x3e;T (p.Asn856Ile), localized in the cytoplasmic tyrosine kinase domain, exhibiting a KOGS phenotype. The coarsening of the facial features, enlargement of the hands/feet, and progressive scoliosis started to appear after an average age of 6. There were no signs of thin/fragile skin, premature aging appearance, myofibroma, white matter findings, and intellectual disability in any of them. Corneal pterygium and evidence of cerebral vasculopathy were only detected in the father. One sibling exhibited café-au-lait spots. Posterior fossa enlargement was revealed only in one sibling. KOGS is an extremely rare overgrowth syndrome. No familial cases of KOGS have been reported so far. Hereby, we demonstrated that the features of KOGS can show mild intrafamilial variability, and the risk of vascular complications may arise with age.

Leopard syndrome: the potential cardiac defect underlying skin phenotypes

LEOPARD syndrome (OMIM #151,100) caused by a germline PTPN11 mutation are characterized as multisystemic anomalies and variable marked phenotypes such as multiple lentigines and cafe´-au-lait spots, electrocardiographic conduction abnormalities, ocular hypertelorism/obstructive cardiomyopathy, pulmonary stenosis, abnormal genitalia, retardation of growth, and deafness. Phenotype overlap complicates clinical discrimination within RASopathies, making the diagnosis of LEOPARD more confusing and challenging. Besides, LEOPARD patients do not usually present with all these typical clinical features, increasing the possibility of underdiagnosis or misdiagnosis.Herein, we report a case of LEOPARD syndrome in a patient who only presented with pigmented skin spots and was initially diagnosed with multiple acquired melanocytic nevi. Subsequent pathological examination confirmed the diagnosis of multiple lentigines rather than melanocytic nevi. A genetic study showed a germline PTPN11 (Tyr279Cys) mutation and raised the suspicion of LEOPARD syndrome. A subsequent ECG examination detected potential cardiac defects and confirmed the diagnosis of LEOPARD. We considered that the potential damage of other systems underlying the skin multiple lentigines should not be ignored. The diagnosis of LEOPARD syndrome in an early stage before cardiac damage has reached a serious and irreversible stage can be meaningful for patients to fully understand the potential risks, complications and prognosis of the disease and to take appropriate precautions to prevent the potential risk of cardiac damage.

Isolated Plexiform Neurofibroma of the Nasal Tip - A Rare Case Report

A 28-year-old female patient presented at ENT OPD with complaints of a slowly growing mass over nasal tip since last 5 years. There were no complaints of pain, nasal obstruction, or epistaxis. There were no skin changes or ulceration over the swelling and sensation was preserved. There was no history of similar kind of swelling in other parts of the body. History of trauma or any form of surgical intervention were excluded. Family history was insignificant. The swelling did not respond to any medications. The patient attended for cosmetic reason solely. Clinical examination showed a soft non-tender 4 cm by 4 cm mass over nasal tip and supratip area. Mobility of the mass was restricted and fixed to the alar cartilages. There was no evidence of café au lait spots or any other skin lesions. Anterior rhinoscopy was unremarkable. Diagnostic nasal endoscopy was also performed but no abnormality was detected. CT scan showed non-specific infiltrative subcutaneous lesions. T1W MRI showed an ill-defined hypodense mass over the nasal tip which was abutting the alar cartilages which showed mild enhancement with contrast (figure 1). T2W MRI showed hyperintense and or hypodense central focus (target sign). FNAC was done and report was suggestive of neurogenic tumour, most probably neurofibroma.

Cafe-au-lait spots as a clinical sign of syndromes

Several studies describe the frequent association of cafe-au-lait spots with neurofibromatosis. However, many other genetic diseases might be associated with the presence of café-au-lait spots. Several genetic diseases are rare. In most cases, syndromes present themselves as a set of signs and symptoms that may present varied penetrance, therefore largely reducing the percentage of final diagnosis. Exploration of clinical symptomatology is essential for the understanding and diagnosis of syndromes. In this review, we conduct an extensive literature search looking for research that investigated diseases that may be present simultaneously with the cafe-au-lait spots. A total of 60 genetic diseases were found, all of them rare. These syndromes were evaluated based on their most relevant features and described in a summary of the typical, general, and head and neck findings. The available OMIM number, mode of inheritance, chromosome, mutated genes, and affected proteins were also listed. The considerable variety of diseases associated with the presence of cafe-au-lait spots and the fact that many of these conditions affect various organ systems with diverse phenotypic presentations is a diagnostic and therapeutic challenge. The objective of this study was to provide health professionals with an instrument containing a broad spectrum of genetic diseases coincident with the presence of cafe-au-lait spots in order to facilitate the differential and final diagnosis of these syndromes.

Severe Phenotype in Patients with Large Deletions of NF1

Complete deletion of the NF1 gene is identified in 5–10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described “classic” NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients.

Neurofibromatosis Type 1 Presenting With Adrenal Pheochromocytoma

Background: Pheochromocytomas & Paragangliomas (PCC/PGL) are amongst the rare endocrine tumours, occurring with an incidence of 0.8 per 100,0001. Though most of them have a benign nature, they are usually hormonally active causing significant cardiovascular morbidity due to the catecholamine secretion. Approximately a third of PCC/PGL have underlying germline mutations including Neurofibromatosis type 1 (NF1). Clinical Case: A 49 year old man was reviewed for symptoms of palpitation, headache, sweating, and blurred vision. physical examination revealed signs of NF1. He had multiple neurofibromas over the skin of the back, chest and neck, café-au-lait spots on the trunk and limbs. Ophthalmology assessment revealed multiple Lisch nodules bilaterally. Urinary catecholamines were significantly elevated. His initial systolic blood pressure was 190/148 mmHg. The patient’s medical history included hypertension that used to be well-controlled with Amlodipine 10 mg and Bisoprolol 5mg. however his blood pressure was harder to control during the past year. Laboratory investigations testing included measurements of urinary fractionated metanephrines which revealed high normetanephrines with a value of 690 nmol/d (N &lt; 240). metanephrines (485 nmol/d: N &lt; 275) and norepinephrines (456 nmol/d: N &lt; 440). Plasma free normetanephrines were 3.20 nmol/L (N &lt;1.20) and free metanephrines 0.4 nmol/L (N &lt; 0.48). CT scan of the abdomen showed a 1.3 x 2.4x 3.9 mass in the left suprarenal gland which showed showed moderate uptake on A meta-iodobenzylguanidine (MIBG) scan. And no evidence of metastases. The patient underwent laparoscopic adrenalectomy of the left suprarenal gland and histopathological examination was confirmatory of pheochromocytoma postoperatively. Conclusion:This is a case demonstrating the association between the germline mutation causing neurofibromatosis type 1 with the rare catecholamine secreting tumour (pheochromocytoma). Reference:1. Lefebvre M, Foulkes WD. Pheochromocytoma and paraganglioma syndromes: genetics and management update. Curr Oncol. 2014;21(1):e8-e17. doi: 10.3747/co.21.1579. [PMC free article] [PubMed] [CrossRef] [Google Scholar]