Impaired catabolism of free oligosaccharides due to MAN2C1 variants causes a neurodevelopmental disorder.

Free oligosaccharides (fOSs) are soluble oligosaccharide species generated during N-glycosylation of proteins. Although little is known about fOS metabolism, the recent identification of NGLY1 deficiency, a congenital disorder of deglycosylation (CDDG) caused by loss of function of an enzyme involved in fOS metabolism, has elicited increased interest in fOS processing. The catabolism of fOSs has been linked to the activity of a specific cytosolic mannosidase, MAN2C1, which cleaves α1,2-, α1,3-, and α1,6-mannose residues. In this study, we report the clinical, biochemical, and molecular features of six individuals, including two fetuses, with bi-allelic pathogenic variants in MAN2C1; the individuals are from four different families. These individuals exhibit dysmorphic facial features, congenital anomalies such as tongue hamartoma, variable degrees of intellectual disability, and brain anomalies including polymicrogyria, interhemispheric cysts, hypothalamic hamartoma, callosal anomalies, and hypoplasia of brainstem and cerebellar vermis. Complementation experiments with isogenic MAN2C1-KO HAP1 cells confirm the pathogenicity of three of the identified MAN2C1 variants. We further demonstrate that MAN2C1 variants lead to accumulation and delay in the processing of fOSs in proband-derived cells. These results emphasize the involvement of MAN2C1 in human neurodevelopmental disease and the importance of fOS catabolism.

Extending the clinical spectrum of X-linked Tonne-Kalscheuer syndrome (TOKAS): new insights from the fetal perspective.

INTRODUCTION: Tonne-Kalscheuer syndrome (TOKAS) is a recessive X-linked multiple congenital anomaly disorder caused by RLIM variations. Of the 41 patients reported, only 7 antenatal cases were described. METHOD: After the antenatal diagnosis of TOKAS by exome analysis in a family followed for over 35 years because of multiple congenital anomalies in five male fetuses, a call for collaboration was made, resulting in a cohort of 11 previously unpublished cases. RESULTS: We present a TOKAS antenatal cohort, describing 11 new cases in 6 French families. We report a high frequency of diaphragmatic hernia (9 of 11), differences in sex development (10 of 11) and various visceral malformations. We report some recurrent dysmorphic features, but also pontocerebellar hypoplasia, pre-auricular skin tags and olfactory bulb abnormalities previously unreported in the literature. Although no clear genotype-phenotype correlation has yet emerged, we show that a recurrent p.(Arg611Cys) variant accounts for 66% of fetal TOKAS cases. We also report two new likely pathogenic variants in RLIM, outside of the two previously known mutational hotspots. CONCLUSION: Overall, we present the first fetal cohort of TOKAS, describe the clinical features that made it a recognisable syndrome at fetopathological examination, and extend the phenotypical spectrum and the known genotype of this rare disorder.

Whole-body MR imaging in suspected physical child abuse: comparison with skeletal survey and bone scintigraphy findings from the PEDIMA prospective multicentre study.

OBJECTIVES: To assess the contribution of whole-body magnetic resonance imaging (WBMRI) and bone scintigraphy (BS) in addition to skeletal survey (SS) in detecting traumatic bone lesions and soft-tissue injuries in suspected child abuse. METHODS: In this prospective, multicentre, diagnostic accuracy study, children less than 3 years of age with suspected physical abuse were recruited. Each child underwent SS, BS and WBMRI. A blinded first review was performed in consensus by five paediatric radiologists and three nuclear medicine physicians. A second review investigated discrepancies reported between the modalities using a consensus result of all modalities as the reference standard. We calculated the sensitivity, specificity and corresponding 95% confidence interval for each imaging modality (SS, WBMRI and BS) and for the combinations [SS + WBMRI] and [SS + BS]. RESULTS: One hundred seventy children were included of which sixty-four had at least one lesion. In total, 146 lesions were included. The sensitivity and specificity of each examination were, respectively, as follows: 88.4% [95% CI, 82.0-93.1] and 99.7% [95% CI, 99.5-99.8] for the SS, 69.9% [95% CI, 61.7-77.2] and 99.5% [95% CI, 99.2-99.7] for WBMRI and 54.8% [95% CI, 46.4-63.0] and 99.7% [95% CI, 99.5-99.9] for BS. Sensitivity and specificity were, respectively, 95.9% [95% CI, 91.3-98.5] and 99.2% [95% CI, 98.9-99.4] for the combination SS + WBMRI and 95.2% [95% CI, 90.4-98.1] and 99.4% [95% CI, 99.2-99.6] for the combination SS + BS, with no statistically significant difference between them. CONCLUSION: SS was the most sensitive independent imaging modality; however, the additional combination of either WBMRI or BS examinations offered an increased accuracy. KEY POINTS: • SS in suspected infant abuse was the most sensitive independent imaging modality in this study, especially for detecting metaphyseal and rib lesions, and remains essential for evaluation. • The combination of either SS + BS or SS + WBMRI provides greater accuracy in diagnosing occult and equivocal bone injuries in the difficult setting of child abuse. • WBMRI is a free-radiation technique that allows additional diagnosis of soft-tissue and visceral injuries.

PHACES Syndrome and Associated Anomalies: Risk Associated With Small and Large Facial Hemangiomas.

OBJECTIVE. PHACES syndrome includes posterior fossa malformations, hemangioma, arterial anomalies, coarctation of the aorta and cardiac defects, eye abnormalities, and sternal defect with or without supraumbilical raphe. Usually, brain imaging is performed when facial hemangiomas are larger than 5 cm. Data on associated anomalies regardless of hemangioma size are sparse. The objective of this study was to determine, first, the prevalence of PHACES-like associated anomalies in a large sample of infants with all sizes of segmental facial or periorbital focal infantile hemangioma and, second, whether the cutaneous localization of the hemangioma correlates with the type of anomalies present. MATERIALS AND METHODS. The records of all patients of a vascular anomalies practice who had a diagnosis of segmental facial or periorbital focal infantile hemangioma and who had clinical photographs and brain MRI available were reviewed. The clinical photographs were reviewed to determine the localization by segment and lateralization. MRI was reviewed by two experienced pediatric radiologists. If present, cardiovascular anomalies, sternal defects, and eye anomalies were recorded. The criteria for definite and possible PHACES were used. RESULTS. The study included 122 children (90 girls, 32 boys; mean age, 16.6 months). Forty-five (36.9%) children had a facial infantile hemangioma larger than 5 cm. Twenty-two patients (18.0%) had PHACES or possible PHACES syndrome. Cerebrovascular structural anomalies were seen in 14 of 22 and brain anomalies in 6 of 22 patients with PHACES syndrome but in none and one of the patients in the group without PHACES (p < .001). Cardiovascular anomalies were seen in six patients and ocular anomalies in eight patients. All but one of them had PHACES syndrome. CONCLUSION. Clinical concern about associated extracutaneous anomalies is warranted for all children with facial segmental or periorbital focal infantile hemangiomas, including those with small hemangiomas. Further studies are needed to correlate cerebrovascular anomalies with the clinical evolution of hemangiomas and their effects on cerebral perfusion.

Performance of diagnostic ultrasound to identify causes of hydramnios.

INTRODUCTION: We aimed to assess the diagnostic yield of ultrasonography in the identification of the etiology of hydramnios, and the added value of MRI or amniocentesis. METHODS: We conducted a single-center retrospective study including pregnancies with confirmed hydramnios (defined as deepest pocket ≥8 cm) between January 2013 and May 2017. Twin pregnancies, secondary hydramnios discovered after the diagnosis of a causal pathology, and pregnancies of unknown outcome were excluded. All pregnancies underwent a targeted scan, and selected cases underwent MRI or amniocentesis. RESULTS: A total of 158 patients with confirmed hydramnios were included. Hydramnios was associated with a fetal pathology in 37 cases (23.4%), with diabetes in 39 (24.6%), isolated macrosomia in 16 (10.1%), and considered idiopathic in 66 (41.7%). Ultrasonography established a diagnosis of the underlying pathology in 73% of cases. Amniocentesis was done in 31 cases (20%) and it allowed diagnosis of chromosome anomalies, esophageal atresia, myotonic dystrophy congenital type, Prader-Willi syndrome, and Bartter syndrome. MRI was done in 15 cases (10%) and it allowed one additional diagnosis of esophageal atresia. The diagnostic yields of MRI and amniocentesis were 91.7% and 95.2%, respectively. There were five false positive diagnoses at ultrasonography, and one false positive diagnosis at MRI. CONCLUSION: Hydramnios can be associated with a wide variety of underlying pathologies. Diagnostic ultrasound can attain a diagnosis in the majority of cases. Amniocentesis offers a valuable complementary assessment.

Pneumosinus dilatans of the sphenoid and visual loss: when should the optic nerve be decompressed?

Pneumosinus dilatans of the sphenoid sinus is a rare disorder which can be responsible for visual impairment and blindness. We present the case of an adolescent female who experienced progressive decrease in right-eye vision over 2 years. CT scan of the head showed an extensive pneumatization of the sphenoid bone extending to the lesser wing of the sphenoid and to the anterior clinoid process on the right side. MRI revealed right nerve atrophy in the optic canal and in the posterior part of the orbit. A surgical decompression of the right optic canal was performed via an intradural fronto-pterional approach. Postoperatively, her vision worsened, and at 3 years the patient was able to count fingers at 2.5 m. Our case and literature review of symptomatic sphenoidal pneumosinus dilatans confirmed that visual prognosis in such cases depended on the preoperative visual status. Early surgical decompression should be proposed whenever possible, before signs of severe visual disorders and optic atrophy.

Dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease) presenting as a prenatally heterotopic hamartoma.

Dysplastic gangliocytoma of the cerebellum (DGC), also called Lhermitte-Duclos disease, is a rare lesion of the posterior fossa consisting of a diffuse hypertrophy of the cerebellar cortex. DGC frequently presents in young adults and rarely in childhood. Only 3 cases have been previously described in newborns. We present an uncommon case of DGC which was diagnosed in utero. The radiological presentation prenatally and at birth was similar to a heterotopic neuroglial brain tissue. MRI aspects evolved from T1/T2 isointense signals to hypoT1 and hyperT2 signals at the age of 1 year. The girl was then operated on total removal of the lesion which was performed with no postoperative complication. Genetics did not demonstrate any germline PTEN mutation or family history suggesting Cowden disease. Two years later, the child was doing well and MRI confirmed complete resection. This case illustrates the difficulties of diagnosing intracranial lesions in foetuses and newborns. Physicians caring for pregnant women and pediatrics should be aware that neoplasm-like lesions such as DGC may present as hamartomas. Surgical resection could then be discussed whenever possible.

Ruptured intracranial arachnoid cysts in the subdural space: evaluation of subduro-peritoneal shunts in a pediatric population.

PURPOSE: Rupture of arachnoid cysts (AC) in the subdural space after trauma may cause a subacute/chronic subdural hematoma or a hygroma. Treatment of this complication still remains controversial, and no consensual strategy is to date clearly proposed. In this study, the authors evaluated the clinical and radiological evolution of patients treated by a subduro-peritoneal shunt for symptomatic subdural collections complicating ruptured AC. METHODS: Medical records of the 10 patients treated at our institution between January 2005 and December 2018 for a subdural collection associated with an intracranial AC were reviewed. Subduro-peritoneal shunts consisted of low-pressure valves from 2005 to 2012 (6 cases) and medium-pressure valves after 2012 (4 cases). RESULTS: A benign head trauma was retrospectively found in the history of 8 patients. The mean time to diagnosis ranged from 15 days to 5 months. Symptoms resulted mainly from intracranial hypertension. Six patients had an ipsilateral hygroma to the AC, 2 patients had a bilateral hygroma predominantly to the AC side, and 2 patients presented an ipsilateral chronic subdural hematoma. Arachnoid cysts were classified as Galassi I in 5 cases and Galassi II in 5 cases. Patients with chronic subdural hematoma were given a medium-pressure valve. Patients with subdural hygroma received a low-pressure valve in 6 cases and a medium-pressure valve in 2 cases. There were no complications during surgical procedures. All patients were rapidly free of symptoms after surgery and were discharged from hospital 1 to 4 days postoperatively. The subdural collection completely disappeared in all cases. In the long term, only 2 patients with low-pressure valves underwent shunt removal without any consequences, while a second surgical procedure was necessary to treat recurrence of intracranial hypertension in the 4 remaining cases. All the medium-pressure valves were removed without problems. The size of the AC was reduced in 3 cases, remained stable in 4 cases, and increased in 3 cases. No patients experienced recurrence of subdural collection during follow-up. CONCLUSIONS: Medium-pressure subduro-peritoneal shunts should be considered as part of the arsenal of surgical strategy in symptomatic ruptured AC in the subdural space. The procedure is simple with a very low morbidity, and it allows rapid improvement of symptoms. Although the shunt is located in the subdural space, we strongly recommend avoiding devices which may create an overdrainage and expose the patient to shunt dependency such as low-pressure shunts.

Fertility, Pregnancy, and Clinical Outcomes after Uterine Arteriovenous Malformation Management.

STUDY OBJECTIVE: To evaluate fertility, pregnancy, and clinical outcomes after uterine arteriovenous malformation (UAVM) management. DESIGN: Single-center retrospective study (Canadian Task Force classification III). SETTING: One referral center. PATIENTS: Twenty-two patients with a UAVM diagnosed by magnetic resonance angiography or computed tomography angiography and managed by expectant management (EM) or uterine arterial embolization (UAE) during the study period were included. INTERVENTIONS: Nine of 22 patients underwent first-intention EM and 13 first-line UAE. Three of 9 EM patients (33.3%) required emergency second-intention UAE for nonresolution of the UAVM and severe genital bleeding. MEASUREMENTS AND MAIN RESULTS: To analyze fertility according to management approach, we defined 2 groups: EM only group (n = 6) and UAE group (n = 16; women who underwent first- or second-intention UAE). Overall, the median age was 29 years (range, 17-43). The mean follow-up after UAVM management was 39 months (range, 1-116). The success rate of the UAE procedure was 87.5% (14/16). Eight of 12 women (66.7%) who wished to conceive became pregnant: 2 of 5 (33.3%) in the EM group and 6 of 7 (85.7%) in the UAE group (p = 1). Overall, 11 patients (50%) conceived: 3 in the EM group (50%) and 8 in the UAE group (50%) (p = .9). The live birth rate was 36.4% (8/22) for the whole population. There were no miscarriages or ectopic pregnancies. The 8 women (72.7%) wishing to conceive who became pregnant all delivered: 1 by cesarean section and 7 by vaginal delivery. Median duration of pregnancy was 39 weeks and 5 days. The remaining 3 women (i.e., women who conceived but did not wish to become pregnant) had therapeutic abortions. One complication was experienced in the EM group (small for gestational age newborn) and none in the UAE group (p = .3). Limitations include retrospective design and small sample size. CONCLUSION: UAE for UAVM is an effective and safe technique. It does not impair fertility, and obstetric prognosis is good.

Idiopathic, heritable and veno-occlusive pulmonary arterial hypertension in childhood: computed tomography angiography features in the initial assessment of the disease.

BACKGROUND: In children, idiopathic and heritable pulmonary arterial hypertension present echocardiographic and heart catheterization findings similar to findings in pulmonary veno-occlusive disease. OBJECTIVE: To provide a systematic analysis of CT angiography anomalies in children with idiopathic or heritable pulmonary arterial hypertension, or pulmonary veno-occlusive disease. We also sought to identify correlations between CT findings and patients' baseline characteristics. MATERIALS AND METHODS: We retrospectively analyzed CT features of children with idiopathic and heritable pulmonary arterial hypertension or pulmonary veno-occlusive disease and 30 age-matched controls between 2008 and 2014. We compared CT findings and patient characteristics, including gene mutation type, and disease outcome until 2017. RESULTS: The pulmonary arterial hypertension group included idiopathic (n=15) and heritable pulmonary arterial hypertension (n=11) and pulmonary veno-occlusive disease (n=4). Median age was 6.5 years. Children with pulmonary arterial hypertension showed enlargement of pulmonary artery and right cardiac chambers. A threshold for the ratio between the pulmonary artery and the ascending aorta of ≥1.2 had a sensitivity of 90% and a specificity of 100% for pulmonary arterial hypertension. All children with pulmonary veno-occlusive disease had thickened interlobular septa, centrilobular ground-glass opacities, and lymphadenopathy. In children with idiopathic and heritable pulmonary arterial hypertension, presence of intrapulmonary neovessels and enlargement of the right atrium were correlated with higher mean pulmonary artery pressure (P=0.011) and pulmonary vascular resistance (P=0.038), respectively. Mediastinal lymphadenopathy was associated with disease worsening within the first 2 years of follow-up (P=0.024). CONCLUSION: CT angiography could contribute to early diagnosis and prediction of severity in children with pulmonary arterial hypertension.

Magnetic resonance imaging in children presenting migraine with aura: Association of hypoperfusion detected by arterial spin labelling and vasospasm on MR angiography findings.

Objective A child presenting with a first attack of migraine with aura usually undergoes magnetic resonance imaging (MRI) to rule out stroke. The purpose of this study was to report vascular and brain perfusion findings in children suffering from migraine with aura on time-of-flight MR angiography (TOF-MRA) and MR perfusion imaging using arterial spin labelling (ASL). Methods We retrospectively included all children who had undergone an emergency MRI examination with ASL and TOF-MRA sequences for acute neurological deficit and were given a final diagnosis of migraine with aura. The ASL perfusion maps and TOF-MRA images were independently assessed by reviewers blinded to clinical data. A mean cerebral blood flow (CBF) value was obtained for each cerebral lobe after automatic data post-processing. Results Seventeen children were finally included. Hypoperfusion was identified in one or more cerebral lobes on ASL perfusion maps by visual assessment in 16/17 (94%) children. Vasospasm was noted within the intracranial vasculature on the TOF-MRA images in 12/17 (71%) children. All (100%) of the abnormal TOF-MRA images were associated with homolateral hypoperfusion. Mean CBF values were significantly lower ( P < 0.05) in visually hypoperfused lobes than in normally perfused lobes. Conclusion ASL and TOF-MRA are two totally non-invasive, easy-to-use MRI sequences for children in emergency settings. Hypoperfusion associated with homolateral vasospasm may suggest a diagnosis of migraine with aura.

Variability in Imaging Practices and Comparative Cumulative Effective Dose for Neuroblastoma and Nephroblastoma Patients at 6 Pediatric Oncology Centers.

The purpose of this study was to estimate the cumulative effective dose (CED) from diagnosis and posttherapy computed tomographic (CT) scans performed on children treated for neuroblastoma or nephroblastoma (Wilms tumor) and to examine the different imaging practices used in 6 regional pediatric oncology centers between January 2010 and December 2013. We analyzed retrospectively the CT scan acquisition data in children aged 10 years or younger at diagnosis. The use of nonionizing imaging modalities was reported. The CT examinations of 129 children, with a mean age at diagnosis of 36 months, treated for 66 neuroblastomas and 63 nephroblastomas, were analyzed. The mean follow-up period was 28 months (minimum, 8 months, maximum, 41 mo). There were 600 CT scans, with a total of 1039 acquisitions. The mean CED from CT scans was 27 mSv (minimum=18.25, maximum=45). Abdominal CT examinations contributed 85% of the total CED. A median of 4.6 CT scans, 10.3 sonograms, and 0.4 magnetic resonance imaging examinations per child were performed. Our results suggest a reduction in radiation exposure but variability in the imaging modality choice and acquisition protocols. We emphasize the need for consensus and standardization in oncologic pediatric imaging procedures. When feasible, we encourage the substitution of nonionizing examinations for CT.

Reversible lesions of the corpus callosum with initially restricted diffusion in a series of Caucasian children.

BACKGROUND: Reversible lesions of the corpus callosum with initial restricted diffusion on diffusion-weighted imaging (DWI) are rare and mainly described in the south Asiatic population. OBJECTIVE: The purpose of this study was to describe the clinical presentation, imaging findings, prognosis and etiology of transient restricted diffusion lesions of the corpus callosum in a series of Caucasian children. MATERIALS AND METHODS: Seven children presenting with a transient restricted DWI lesion of the corpus callosum were included. Their clinical presentations and paraclinical examinations were investigated in addition to their MRI findings during the acute phase and at follow-up. RESULTS: Five patients initially presenting with prodromal flu-like symptoms were diagnosed with mild encephalopathy with reversible corpus callosum lesions, three of which were due to the influenza virus. For two patients (twins) with a stroke-like presentation and without febrile illness, a central nervous system manifestation of X-linked Charcot-Marie-Tooth disease with connexin 32 mutation was diagnosed. All patients had a good clinical prognosis without clinical sequelae or residual MRI lesion for all patients at follow-up. CONCLUSION: A transient lesion of the corpus callosum with restricted diffusion should prompt the radiologist to suggest an infectious trigger in children. The prognosis of these patients was good with normalization of clinical symptoms and MRI without any specific treatment.

Intradiploic growing skull fracture: review of mechanisms and literature.

PURPOSE: A rare case of intradiploic growing fracture of the occipital bone is presented. Examination of this case and literature review was carried out to find significant specific features of such a rare condition. CASE: A 4-year-old boy was operated on for a huge occipital intradiploic growing skull fracture. His medical history, surgical management, and postoperative course are presented. LITERATURE REVIEW: A computer literature search using the Medline database revealed 31 well-documented cases. CONCLUSIONS: Special attention must be paid to skull fractures in childhood when occurring near CSF large spaces, especially if ventricle enlargement, suggesting that hydrocephalus is present. Surgeons should evaluate hydrocephalus before treating such lesions in order to improve surgical result and postoperative clinical evolution.

Comparison of early and late MRI in neonatal hypoxic-ischemic encephalopathy using three assessment methods.

BACKGROUND: There is no consensus on the optimum timing of MRI in neonates with hypoxic-ischemic encephalopathy treated with hypothermia. Reliable early imaging assessment might help managing treatment. OBJECTIVE: To assess non-random differences between early and late MRI that might influence intensive-care decisions. MATERIALS AND METHODS: This single-center retrospective study included all asphyxiated term neonates eligible for hypothermia treatment November 2009-July 2012. MRI scans were systematically performed at day 4 (early MRI) and day 11 of life as part of routine protocol. Two experienced pediatric radiologists reviewed both scans according to three assessment methods: a pattern classification, a scoring system and a simplified classification. Agreement between early and late imaging findings was assessed using Cohen's kappa coefficients. RESULTS: Thirty-three neonates were included. Interobserver agreement was excellent. Early MRI detected all severe injuries. Agreement between early and late MRI was excellent for the simplified classification (κ = 0.82), good for the pattern classification (κ = 0.64), and good to excellent for 3 scores out of 4 in the scoring system (κ = 0.70-0.89). CONCLUSION: Early MRI may provide valuable information about brain injury to help parents and neonatologists in intensive-care decisions at the end of hypothermia treatment.

Imaging of musculoskeletal disorders related to pregnancy.

OBJECTIVE: This article provides an overview of the typical appearance of biomechanical and physiologic changes in pregnancy and an update on related pathophysiology. Conditions occurring during the childbearing, delivery and postpartum periods will be reported separately. CONCLUSION: Pregnancy causes biomechanical and physiologic changes that may be responsible for a wide spectrum of musculoskeletal disorders in the mother.

Whole-body post-mortem computed tomography compared with autopsy in the investigation of unexpected death in infants and children.

OBJECTIVES: To investigate the contribution of whole-body post-mortem computed tomography (PMCT) in sudden unexpected death in infants and children. METHODS: Forty-seven cases of sudden unexpected death in children investigated with radiographic skeletal survey, whole-body PMCT and autopsy were enrolled. For imaging interpretation, non-specific post-mortem modifications and abnormal findings related to the presumed cause of death were considered separately. All findings were correlated with autopsy findings. RESULTS: There were 31 boys and 16 girls. Of these, 44 children (93.6 %) were younger than 2 years. The cause of death was found at autopsy in 18 cases (38.3 %), with 4 confirmed as child abuse, 12 as infectious diseases, 1 as metabolic disease and 1 as bowel volvulus. PMCT results were in accordance with autopsy in all but three of these 18 cases. Death remains unexplained in 29 cases (61.7 %) and was correlated with no abnormal findings on PMCT in 27 cases. Major discrepancies between PMCT and autopsy findings concerned pulmonary analysis. CONCLUSIONS: Whole-body PMCT may detect relevant findings that can help to explain sudden unexpected death and is essential for detecting non-accidental injuries. We found broad concordance between autopsy and PMCT, except in a few cases of pneumonia. It is a non-invasive technique acceptable to relatives. KEY POINTS: • Whole-body post-mortem computed tomography (PMCT) is an effective non-invasive method. • Whole-body PMCT is essential for detecting child abuse in unexpected death. • There is concordance on cause of death between PMCT and autopsy. • Whole-body PMCT could improve autopsy through dissection and sampling guidance. • PMCT shows findings that may be relevant when parents reject autopsy.

PHGDH-related microcephalic dwarfism in two fetuses: Expanding the phenotypical spectrum of L-serine biosynthesis defect.

Defects in L-serine biosynthesis are a group of autosomal recessive diseases resulting in a wide phenotypic spectrum ranging from viable to lethal presentations and caused by variants in the three genes encoding the L-serine biosynthesis enzymes, PHGDH, PSAT1, and PSPH. Neu-Laxova syndrome (NLS) is the fetal form of this group, characterized by multiple congenital anomalies including severe intrauterine growth retardation, cutaneous lesions extending from ichthyosis to severe restrictive dermopathy with ectropion and eclabion, edema, microcephaly, central nervous system abnormalities, and flexion contractures. Here we report on two unrelated fetuses with an attenuated phenotype of NLS, that initially evoked Taybi-Linder syndrome. They carry biallelic pathogenic variants in the PHGDH gene. These observations expand the phenotypic continuum of L-serine biosynthesis defects, and illustrate the phenotypic overlap between NLS and microcephalic primordial dwarfism.

Snapping knee: imaging findings with an emphasis on dynamic sonography.

OBJECTIVE: The purpose of this article is to illustrate the causes of snapping knee. The value of imaging techniques is discussed with an emphasis on dynamic sonography in light of the available surgical and radiologic literature. CONCLUSION: Because of its dynamic capabilities, dynamic sonography provides real-time visualization of snapping knee syndrome and may be used as a first-line modality.