Left Axilla Research Articles

036. Sclerotic Therapy as The Management Of Arteriovenous Malformation on Hand: A Case Report

Background: An arteriovenous malformation (AVM) is an abnormal connection between arteries and veins, bypassing the capillary system. There are a number of consequences associated with this illness, such as bleeding and neurological impairments. The situation is complex, which emphasizes the necessity for individualized treatment plans. This case report a 18 years old female with AVM condition. Case: A 18 years old female was admitted to to Prof. IGNG Ngoerah General Hospital with a chief complaint of lump on the left finger. The lump on the left finger has been felt since >10 years ago. The lump appeared suddenly and went bigger each day. Complaints worsened until the patient felt pain in the left finger. On examination of the local status, multiple masses were found on third and fourth digits of the left hand, with unclear border and vein ectasis. MSCT Angiography of the left superior extremity found a soft tissue image of hemangioma on the palmar aspect and interdigiti III-IV to the palmar-dorsal aspect of digit III and the palmar aspect of digiti IV of the left hand and multiple non-suspicious lymphadenopathy in the left axilla region. The scleroterapy treatment was performed and 3 months results shown decreased size of the masses without any complication. Conclusion: An arteriovenous malformation (AVM) of the left hand fingers is a rare case found in Prof Ngoerah Hospital. The sclerotic therapy found to be an effective management for this case.

A Unique Case of Unilateral Pseudogynecomastia.

Gynecomastia is a common condition characterized by the benign enlargement of male breast tissue, often resulting from hormonal imbalances. A rare variant, unilateral pseudogynecomastia, involves enlargement due to adipose tissue accumulation without glandular proliferation and can be associated with occupational factors. We report the case of a 45-year-old male mechanic presenting with unilateral enlargement of the left breast. The patient reported daily microtrauma on his left axilla and chest wall. The clinical evaluation and imaging revealed lipomatosis with pronounced fibrous tissue and no glandular tissue involvement. The hormonal assays were within the normal limits. The patient underwent surgical excision of excess adipose tissue using the Kornstein technique, preserving the nipple-areola complex. The histopathological examination confirmed the absence of malignancy. The postoperative recovery was uneventful, and the follow-up examination at 12 months demonstrated a symmetrical breast appearance with no recurrence. This case underscores the importance of differentiating pseudogynecomastia from true gynecomastia and recognizing potential occupational risks. Surgical management using techniques that preserve the nipple-areola complex can achieve excellent cosmetic outcomes.

Case report: segmental form of Hailey-Hailey disease

The article presents a clinical case of a rare segmental form of familial benign chronic pemphigus with a positive family history. Patient S., born in 2014, complained of unilateral eruptions in the area of the left retroauricular fold, left axilla, inguinal fold and labia majora on the left, plantar surface of the left foot. Eruptions were represented by erythematous foci, single blisters with serous contents, erosions, crusts. For the entire period, the patient was observed with the following diagnoses: microbial eczema, Sneddon-Wilkinson Disease, Inflammatory Linear Verrucose Epidermal Nevus. Due to the long-term relapsing course and ineffective therapy, additional examination methods were carried out – histological and genetic studies. Only after genetic testing, in which a heterozygous mutation of the ATP2C1 gene was revealed, and geneticist’s consultation, the final diagnosis was established – Hailey-Hailey Disease.It is known, that the segmental form is formed as a result of mosaicism, which can be of two types. The term "mosaicism" refers to the presence in an organism of two or more genetically heterogeneous cell populations formed from a genetically homogeneous zygote. The formation of type 1 mosaicism is based on a de novo postzygotic mutation at an early stage of embryogenesis. In turn, type 2 mosaicism develops as a result of a postzygotic mutation against the background of an already existing prezygotic mutation. Determining the type of mosaicism by genetic testing will make it possible to assess the prognosis of the disease and the chance of transmitting this disease to offspring.

Primary BAP1-absent atypical meningioma arising from median nerve within infraclavicular brachial plexus: illustrative case.

The authors present the only known case of a World Health Organization grade II ectopic meningioma occurring in the infraclavicular brachial plexus, causing pain within the axilla not associated with a primary malignant meningioma of the central nervous system. Peripheral nerve sheath tumors are rare entities, the majority of which are schwannomas or neurofibromas. Ectopic meningiomas only represent 1%-2% of all meningiomas. To date, there is one other published case specifically of a primary ectopic meningioma located in the brachial plexus. Following the dissection of the left axilla, a dominant rubbery tumor involving the median nerve was encountered. The tumor capsule contained areas of hemorrhage and a soft core with nerve fascicles coursing through, which were not compromised during internal tumor debulking. The tumor lacked a clear pseudocapsule that is characteristically seen in schwannomas. Histopathological studies confirmed an atypical epithelioid neoplasm with elevated numbers of mitotic figures and BAP1 gene deletion. Primary meningiomas arising outside the central nervous system are exceedingly rare. For this unusual higher-grade primary ectopic meningioma located in the distal brachial plexus, surgery with the goal of gross-total resection, adjuvant radiation, additional imaging, and genetics screening were recommended. Close follow-up is warranted. https://thejns.org/doi/10.3171/CASE24226.

A case of scrub typhus with meningitis as the onset: Case report and literature review.

Scrub typhus is a naturally occurring acute febrile disease caused by Orientia tsutsugamushi. Although it can cause multiple organ dysfunction, central nervous system infections are uncommon. A 17-year-old male presented with a 5-day history of fever and headaches. The MRI of the head revealed thickness and enhancement of the left temporal lobe and tentorium cerebelli, indicating potential inflammation. The patient was diagnosed with a central nervous system infection. Ceftriaxone and acyclovir were administered intravenously to treat the infection, reduce fever, restore acid-base balance, and manage electrolyte disorders. Despite receiving ceftriaxone and acyclovir as infection therapy, there was no improvement. Additional multipathogen metagenomic testing indicated the presence of O tsutsugamushi infection, and an eschar was identified in the left axilla. The diagnosis was changed to scrub typhus with meningitis and the therapy was modified to intravenous doxycycline. Following a 2-day therapy, the body temperature normalized, and the fever subsided. The patient was diagnosed with scrub typhus accompanied by meningitis, and doxycycline treatment was effective. Rarely reported cases of scrub typhus with meningitis and the lack of identifiable symptoms increase the chance of misdiagnosis or oversight. Patients with central nervous system infections presenting with fever and headache unresponsive to conventional antibacterial and antiviral treatment should be considered for scrub typhus with meningitis. Prompt multipathogen metagenomic testing is recommended to confirm the diagnosis and modify the treatment accordingly.

Primary Cutaneous Apocrine Carcinoma: Diagnostic and Management Difficulties of an Uncommon Neoplasm

Primary cutaneous apocrine carcinoma (PCAC) is a rare adnexal neoplasm. Due to its clinical presentation, it can mimic other tumors, especially metastasis. We present a case of primary apocrine carcinoma of the axilla mimicking breast carcinoma metastasis in a 54-year-old woman. The patient presented with a painless, lobed, and erythematous nodule in the left axilla of one year duration. We suspected an adnexal neoplasm but also considered metastasis from breast carcinoma. Histological examination revealed apocrine proliferation. Immunohistochemistry stains of tumor cells were positive for AE1/AE3, and negative for CK7, CK20, p63 and GATA3. Radiological explorations did not reveal any signs of malignancy. Considering all these features, the conclusive diagnosis was primary cutaneous apocrine carcinoma. Treatment was wide excision without adjuvant therapy, and no recurrence was noted. Due to the rarity of this carcinoma, its various clinical presentations, and histological overlaps with breast cancer metastasis, making the diagnosis may be challenging. A comprehensive evaluation of all findings is necessary to rule out other tumors. There is any consensus on the management strategy. The standard treatment is surgical excision, but adjuvant therapies such as radiotherapy or chemotherapy can be proposed in advanced stage disease.

Metaplastic breast cancer with a unique presentation and complete response to chemotherapy: a case report

BackgroundMetaplastic breast carcinomas are a rare variant group of breast carcinomas. They are usually high-grade and triple-negative tumors. They often present with large primary tumor sizes. However, the involvement of axillary lymph nodes is infrequent at the time of diagnosis. Metaplastic breast carcinomas are associated with a worse prognosis and a poorer response to chemotherapy in comparison with other non-metaplastic triple-negative breast cancers. Up until this point, there are no specific treatment recommendations for metaplastic breast carcinomas beyond those intended for invasive breast cancer in general.Case presentationA 40-year-old woman complained of a palpable mass in her left axilla. On ultrasonography, the mass was solid, spindle-shaped, hypoechoic with regular borders, and exhibited decreased vascularity. At first, the mass appeared to be of a muscular origin. There was not any clinical nor ultrasonic evidence of a primary breast tumor. On magnetic resonance imaging, the axillary mass was a well-defined with regular borders, measuring 24 × 35 mm. Needle biopsy showed a spindle cell tumor with mild to moderate atypia. The subsequent surgical resection revealed a spindle cell neoplasm within a lymph node, favoring a metastatic origin of the tumor. The tumor cells lacked expression of estrogen, progesterone, and HER2 receptors. PET-CT scan indicated pathological uptake in the left breast. Accordingly, the patient was diagnosed with metaplastic breast cancer that had metastasized to the axillary lymph node. She commenced a combined chemotherapy regimen of doxorubicin and cyclophosphamide. After six treatment cycles, she underwent left modified radical mastectomy with axillary lymph node dissection. Pathological examination of the specimens revealed a total burn-out tumor in the breast due to excellent treatment response. There were no residual tumor cells. All dissected lymph nodes were free of tumor. At the one-year follow-up, the patient showed no signs of tumor recurrence.ConclusionThis report sheds light on a distinctive presentation of metaplastic breast carcinoma, emphasizing the need for vigilance in diagnosing this rare and aggressive breast cancer variant. In addition, the patient’s remarkable response to chemotherapy highlights potential treatment avenues for metaplastic breast cancer.

An unusual relationship between the axillary artery and brachial plexus in a cross-breed dog cadaver: a proposal for revising the terminology for nerve loops

In the left axilla of a formalin-embalmed adult female cross-breed dog, an unusual course of the axillary artery in relation to the brachial plexus was noted. A part of the axillary artery after the origin of the subscapular artery coursed through the loop formed by the contributions of the caudal pectoral and lateral thoracic nerves and then between the median and ulnar nerves. Thus, the common trunk for the latter two nerves was missing. Instead, in the proximal brachium, they communicated with each other in both directions. A communicating branch between the cranial and caudal pectoral nerves forming a nerve loop, ansa pectoralis lacked the axillary artery and was instead traversed by the subscapular artery. This is a variation in the relationship between the axillary artery and brachial plexus in the domestic dog and has not been reported in the literature yet. The axillary artery entrapped by the contributions of the caudal and lateral thoracic nerves may be considered as a risk factor for the neuroarterial compressions with non-specific signs and should be taken into account both in surgery and imaging.

The concomitant occurrence of hidradenitis suppurativa and Fournier’s gangrene

Background: Fournier’s gangrene represents a life-threatening necrotising infection affecting the perineal region, while hidradenitis suppurativa is characterised by a chronic inflammatory skin condition. The simultaneous occurrence of both conditions is exceedingly rare. Case description: A 42-year-old female with a documented history of severe untreated hidradenitis suppurativa presented for shortness of breath, fever and lethargy, along with extensive wounds and skin breakdown involving the left axilla, perineum, lower back, lumbosacral region and bilateral gluteal areas, extending to the perineum. Upon presentation, the patient was in a state of septic shock, and a diagnosis of actively manifesting Fournier’s gangrene was established at the site of the pre-existing hidradenitis suppurativa lesions. Despite the implementation of an aggressive multidisciplinary approach incorporating surgical interventions, antibiotic therapy and intensive care measures, the patient’s condition deteriorated, culminating in septic shock, multi-organ failure and eventual demise. In this report, we discuss both clinical entities, their similarities and differences, and the possible mechanisms by which they may have co-occurred. Conclusion: The co-existence of hidradenitis suppurativa and Fournier’s gangrene poses unique challenges, given the rapid progression of Fournier’s gangrene within the context of hidradenitis suppurativa, potentially suggesting the latter as a predisposing factor. This case underscores the importance of vigilant screening and management of hidradenitis suppurativa.

SOLAMEN syndrome in a toddler

BackgroundSegmental overgrowth, lipomatosis, arteriovenous malformation, and epidermal nevus (SOLAMEN) syndrome is a segmental overgrowth syndrome that is part of Cowden’s Syndrome, a subset of the PTEN hamartoma tumor syndrome cluster. Due to SOLAMEN disease’s rarity, clinical suspicion should arise if multiple small nonspecific variably low-attenuated nodular lesions in the back, shoulders, and upper arms are present on CT, which are associated with mucocutaneous lesions. We present a rare case of SOLAMEN syndrome with widespread lipomatous growth, greater than reported in literature, with confirmed PTEN genetic testing.Case presentationWe describe a case of a 2-year-old boy with a slowly growing left neck mass since birth. Physical exam revealed macrocephaly and epidermal nevi on left axilla, arm, and fingers, appearing as pink verrucous and has visible veins on chest wall/abdomen. CT and MRI imaging showed a lipomatous hibernoma extending from the leftward neck to the abdominal cavity, encasing vascular structures form the left carotid and subclavian arteries to the diaphragmatic hiatus, in addition to the spleen and kidney. Biopsy of the left shoulder revealed hibernoma, a fatty neoplasm of benign brown fat. Patient had a resection of his left shoulder hibernoma and is currently asymptomatic, undergoing surveillance.ConclusionDue to SOMAMEN syndrome’s rarity, clinical suspicion should arise if a patient presents with multiple small-nonspecific variably low-attenuated nodular lesions on CT and mucocutaneous lesions. Ongoing monitoring should be done as there is an increased risk of cancer.

Consideration of the process of lymph node metastasis in invasive breast cancer with squamous cell differentiation

Abstract Background Breast cancer with squamous differentiation is a relatively rare condition. Clinically, lymph node metastasis is uncommon in metaplastic carcinoma We treated a patient with lymph node metastasis of the ductal carcinoma component of invasive ductal carcinoma with squamous cell differentiation. Case Report An 84-year-old postmenopausal Japanese woman had a left-breast mass with an enlarged lymph node in the left axilla. A biopsy revealed an invasive ductal carcinoma with squamous cell differentiation. A left mastectomy with axillary lymph node dissection was performed. The Histological evaluation revealed invasive ductal carcinoma with squamous cell differentiation. One lymph node was positive for metastasis consisting of ductal carcinoma without squamous cell differentiation. Conclusion This case suggests that lymph node metastasis in ductal carcinoma with squamous differentiation may first involve the ductal carcinoma component and then differentiation may occur in the in volved lymph nodes. This is an interesting case highlighting the process of the progression of lymph node metastasis in cases with breast cancer with squamous cell differentiation.

A case of retroperitoneal capillary malformation examined by contrast-enhanced ultrasonography with perfluorobutane (Sonazoid®)

A man in his 60s with hyperamylasemia underwent contrast-enhanced computed tomography, which revealed masses in his pelvic cavity on the right side and in the left axilla. Hence, a detailed examination was performed. Upon performing Sonazoid® (perfluorobutane) contrast-enhanced ultrasound, it was discovered that the right-sided pelvic cavity mass exhibited centripetal contrast-enhancement right from the early stage. Subsequently, the contrast material disappeared from the center and was washed out in the postvascular phase. The mass was suspected to be caused by vascular malformations. The right-sided pelvic cavity mass was excised, and upon histopathological examination, it was detected to be composed of capillary malformations. Thus, it was found that Sonazoid® contrast-enhanced ultrasound examination could aid in diagnosing retroperitoneal masses.

Benign phyllodes tumor arising from accessory breast tissue of the axilla: An inquisitive rarity

Abstract Accessory breast tissue is the superfluous tissue that persists from normal embryological development. The pathological involvement of this tissue is quite uncommon and can be diagnostically challenging. Phyllodes tumor is a rare mammary fibroepithelial lesion that has been seldom reported to originate from the accessory breast tissue. This article describes an extremely rare case of a benign phyllodes tumor arising from the accessory breast tissue of the left axilla in a 40-year-old female so as to create awareness about rare tumors occurring within rare anomalies.

A clinical case series of Rickettsia spp. from southern Türkiye

Rickettsial infections should be considered in the presence of a maculopapular rash, especially in the endemic area with a history of tick bite. In this study, Rickettsia spp. infections of three cases will be mentioned. Three cases with positive Rickettsia spp immunofluorescent antibody serology were included in the study. Case-1 was a 17-year-old male patient, who had a history of tick bite one week before the admission was admitted with chest pain. He had tachycardia and a "tache noir" rash with a necrotic center in the area of the tick bite. Laboratory parameters showed lymphopenia, cardiac enzymes elevation. The patient’s serelogy of Rickettsia conorii IgM was 1/192 titer positive and IgG was negative. He hospitalized as acute Mediterranean Spotted Fever myocarditis. He recovered with doxycycline treatment. Case-2 was a nine-month-old girl presented with fever, rash and lymphadenomegaly on left axilla two weeks after the tick bite of her left arm. The rash was localized to the arm. R. slovaca and R. aeschlimannii serologies were detected 1/40 titer positive. After ciprofloxacin treatment her symptoms had dissapeared. Case-3 was a seven-year-old girl presented with fever reaching 39ºC for five days, myalgia and rash all over her body. She had scratched the tick from the scalp five days before the admission. Rickettsia conorii IgM serology was 1/768, IgG was 1/640 titer positive. She recovered after doxycycline treatment. Rickettsia spp. infections can lead to infections like myocarditis or the spotted fever group Rickettsiosis diseases. Complications can be prevented with early diagnosis and treatment.

Reconstituted and frozen botulinum toxin A is as effective and safe as fresh for treating axillary hyperhidrosis: A retrospective study.

The use of reconstituted and frozen left-over botulinum toxin A, for treatment of patients with axillary hyperhidrosis seems to be common practice in healthcare. Thus, the objective of this study was to investigate the efficacy and safety of frozen and thawed versus fresh reconstituted abobotulinum toxin (Dysport®) and onabotulinum toxin (Botox®) in the treatment of axillary hyperhidrosis. A retrospective study was conducted analysing efficacy and data from pre- and 24 weeks post-treatment questionnaires together with medical records of individuals with moderate to severe axillary hyperhidrosis. The patients had received fresh prepared botulinum toxin A in their right axilla while frozen and thawed botulinum toxin A had been administered in their left axilla. Treatment was conducted at our Hyperhidrosis Clinic, Umeå University Hospital, Sweden 2019-2021. Pre- and post-treatment questionnaires from 106 patients were analysed. The patients were 18 to 55 years old, with a mean age of 30.7 ± 9.9 years. No significant differences in patient-reported variables, Hyperhidrosis Disease Severity Scale and VAS 10-point scale, were found between the different preparations (frozen compared to fresh) for abobotulinum toxin and onabotulinum toxin, before treatment and at 6 months follow-up. Multivariable regression analysis resulted in no significant difference regarding side-effects between the preparations or brands of botulinum toxin. The findings of this study support our clinical experience that both abobotulinum toxin and onabotulinum toxin, reconstituted, frozen and thawed, seem to be as effective and safe as fresh prepared botulinum toxin when treating axillary hyperhidrosis. Our findings indicate that left-over preparations of abo- and onabotulinum toxins, stored and frozen for up to 6 months, is a cost-and time-effective way of handling botulinum toxin for treatment of axillary hyperhidrosis.

Benign subcutaneous emphysema after insect bite

A 16-year-old girl presented to the emergency department with a several days history of insect bite to the dorsal aspect of the left hand. Initially the swelling was localized to the dorsal hand, over the following four days the swelling became more diffuse involving the whole left forearm, arm, axilla and left hemithorax. She reported no fever.

Cutaneous metastasis from cervical cancer to the scalp and trunk: a case report and review of the literature

BackgroundAn estimated 119,300 new cases of cervical cancer occur annually in China, accounting for 372,00 deaths. Cutaneous metastasis from cervical cancer is a rare event, with an incidence of 0.1–1.3% and typically a preterminal occurrence. Scalp metastasis from cervical cancer is exceptionally anecdotal, with only a dozen examples well documented.Case presentationThe patient is a 33-year-old Chinese woman who was diagnosed with International Federation of Gynecology and Obstetrics stage IVB cervical cancer in November 2021. From December 2021 to April 2022, the patient was enrolled in the clinical trial of sintilimab combined with chemotherapy and radiotherapy for treatment of stage IV cervical cancer and underwent six cycles of immunotherapy and chemotherapy (sintilimab plus paclitaxel liposome and cisplatin). Treatment was well tolerated and led to a partial response. The masses adjacent to the spine and iliac bone was largely reduced. Thus, radiotherapy of the metastatic residues was carried out and followed by radiotherapy to the primary tumor at the cervix uteri. However, by the time of the radiotherapy completion in October 2022, the patient noticed painless nodules at the left scapular region and the right hypochondrium. The following month, more nodules occurred on the scalp and trunk, including the left axilla, anterior abdomen, and left back, along with a lesion invading the sternum that caused acute bone pain. The cutaneous masses were white, discrete with a rubbery consistency, and fixed to the skin. Several nodules increased in size and eventually ulcerated. Fine‑needle aspiration cytology of the left back swellings revealed metastatic squamous cell carcinoma, P16 positive. No visceral or brain metastasis was observed at this point.ConclusionsCervical cancer metastases to the scalp are extremely uncommon. When a scalp metastasis is present, it might be the only symptomatic sign of disease progression or widespread metastatic lesions. So far, there is no clear guideline regarding skin metastases treatment. Such skin lesions warrant a thorough radiologic and pathologic workup to form a comprehensive management plan.

Mitral Valve Prolapse, Not Always an Easy Diagnosis

Abstract We present the case of a 61-year-old male patient, with no medical history, who was presenting for an anterior chest pain, which appeared suddenly during an effort, accompanied by palpitations, fatigue and dyspnea Physical examination revealed the presence of a 4/6 systolic murmur with maximal auscultation at the apex and radiation in the left axilla. Echocardiographic evaluation revealed diagnostically suggestive elements for severe posterior mitral valve prolapse without any rupture, color Doppler showing severe mitral regurgitation, a tricuspid valve prolapse, tricuspid regurgitation grade III and pulmonary hypertension. Coronary angiography revealed coronary arteries without hemodynamically significant lesions, and Holter ECG/24-hour monitoring detected atrial fibrillation in 44% of the monitoring time. In this context, the possible causes of the anterior chest pain were: microvascular angina, traction on the chordae or pulmonary hypertension. The patient had a surgical indication for mitral valve replacement or reconstruction. The department of cardiac surgery undergoes mitral valve replacement with a mechanical prosthesis with a favorable outcome.

Advanced Appendiceal Cancer with Systematic Metastasis without Gastrointestinal Symptoms Found by Subcutaneous Tumor.

An 86-year-old woman with a subcutaneous nodule in her left axilla visited our hospital. She had no gastrointestinal symptoms, but contrast-enhanced computed tomography revealed a cecal mass and systemic metastasis, including cutaneous, bone, peritoneal dissemination and ascites. Colonoscopy revealed a circumferential, elevated cecal lesion. She underwent right hemicolectomy to prevent colon obstruction. The pathological diagnosis was poorly differentiated adenocarcinoma (por1>tub2>muc) arising from the appendix with a BRAFV600E mutation and microsatellite instability-high. Chemotherapy was administered, and she is currently still alive and undergoing chemotherapy. We describe a rare case of advanced appendiceal cancer without gastrointestinal symptoms diagnosed due to cutaneous metastasis.

Klippel–Trenaunay–Weber Syndrome—Case Report: Diagnostic Role of Fetal Autopsy and Histopathology

Abstract Objectives The aim of this study was to evaluate a case of Klippel–Trenaunay–Weber Syndrome (KTWS) diagnosed at 15 weeks of gestation. Materials and Methods A 30-year-old G4P1L1A2 at 15 weeks gestation was detected with abnormal fetal right lower limb thickness and hypervascularity in both thighs. Multiseptated hypoechoic areas were detected involving skin and subcutaneous tissue of the left shoulder region, axilla, chest wall, and lower back region posteriorly extending into both lower limbs associated with cortical thickening of long bones of the lower limb. Significant subcutaneous thickening was present in the right foot along with a slow flow vascular malformation. The couple did not opt for any prenatal testing and continued the pregnancy. Results The patient received routine antenatal care and at 27 weeks of gestation there was polyhydramnios with fetal demise. She delivered a macerated stillborn baby girl weighing 2.5 kg (>99th centile). Consent was obtained for external autopsy, fetal photographs, and tissue biopsy. The fetus was grossly macerated. The skin was hypertrophied and subcutaneous tissue along with bluish discoloration was present over the affected areas. Histopathology of fetal thigh tissue was suggestive of arteriovenous malformation compatible with a diagnosis of KTWS. Conclusions KTWS has unique sonographic features. Confirmation can be done by clinical exome sequencing of amniotic fluid or fetal tissue.