Infant developmental profile of Crisponi syndrome due to compound heterozygosity for CRLF1 deletion

Schierz, Ingrid Anne Mandy; Serra, Gregorio; Antona, Vincenzo; Persico, Ivana; Corsello, Giovanni; Piro, Ettore

doi:10.1097/mcd.0000000000000325

Cited by 30 publications

(14 citation statements)

References 10 publications

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“…To date, only 44 variants in CRLF1 were revealed in 88 patients in the literature, 26 of whom were from Turkey 8,15–17 . Regarding the variants of KLHL7 , only 13 have been identified in 21 patients so far, two of whom participated in the present study 11–13,18–21 …”

Section: Introductionmentioning

confidence: 85%

“…14 To date, only 44 variants in CRLF1 were revealed in 88 patients in the literature, 26 of whom were from Turkey. 8,[15][16][17] Regarding the variants of KLHL7, only 13 have been identified in 21 patients so far, two of whom participated in the present study. [11][12][13][18][19][20][21] In this study, we present the molecular basis of CS/CISS-like phenotypes in 23 clinically well-characterized patients, combining data gathered from two centers in Turkey.…”

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confidence: 99%

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Clinical and molecular genetic findings of Crisponi/cold‐induced sweating syndrome (CS/CISS) spectrum in patients from Turkey

et al. 2022

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Crisponi/cold-induced sweating syndrome (CS/CISS) is a rare autosomal recessive disorder characterized by episodic hyperthermia, arthrogryposis, impaired feeding ability, and respiratory distress. The classic CS/CISS is mainly associated with CRLF1 and, rarely, CLCF1. PERCHING syndrome, previously known as CS/CISS type-3 associated with biallelic pathogenic variants in KLHL7, is notable for its few overlapping manifestations. This study presents genotype-phenotype relationships in CS/CISSlike spectrum associated with CRLF1 and KLHL7. Clinical findings of 19 patients from 14 families and four patients from three families were found in association with six different CRLF1 and three different KLHL7 variants, respectively. c.167T>C and c.713delC of the CRLF1 gene and the c.642G>C of the KLHL7 were novel. The c.708_709delCCinsT allele of CRLF1 was identified in 10 families from the Mardin province of Turkey, underlining that an ancestral haplotype has become widespread.CRLF1-associated phenotypes revealed novel manifestations such as prenatal oligohydramnios, benign external hydrocephalus, previously unreported dysmorphic features emerging with advancing age, severe palmoplantar keratoderma and facial erythema, hypopigmented macules and streaks, and recurrent cardiac arrests. KLHL7 variants presented with glabellar nevus flammeus, blepharophimosis, microcephaly, thin corpus callosum, and cleft palate. Abnormalities of sweating, observed in one patient reported herein, is known to be very rare among KLHL7-related phenotypes.

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Section: Introductionmentioning

confidence: 85%

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confidence: 99%

Clinical and molecular genetic findings of Crisponi/cold‐induced sweating syndrome (CS/CISS) spectrum in patients from Turkey

et al. 2022

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“…Clinicians may suspect DA based on suggestive (also prenatal) clinical findings, which must be then confirmed by NGS analysis [18][19][20][21][22]. Since natural history varies widely among different DA disorders, identification of the underlying causal variant is essential.…”

Section: Discussionmentioning

confidence: 99%

Distal Arthrogryposis type 5 in an Italian family due to an autosomal dominant gain-of-function mutation of the PIEZO2 gene

et al. 2022

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Background Arthrogryposis multiplex congenita (AMC) is a group of clinically and etiologically heterogeneous conditions, characterized by prenatal onset contractures affecting two or more joints. Its incidence is about 1 in 3000 live births. AMC may be distinguished into amyoplasia, distal and syndromic arthrogryposis. Distal arthrogryposis (DA) predominantly affects hands and feet. It is currently divided into more than ten subtypes (DA1, DA2A/B, DA3–10), based on clinical manifestations, gene mutations and inheritance pattern. Among them, only a few patients with DA5 have been reported. It is associated to a gain-of-function pathogenic variant of the PIEZO2 gene, encoding for an ion-channel necessary to convert mechanical stimulus to biological signals and crucial for the development of joints, neuromuscular and respiratory systems. Main clinical features include multiple distal contractures, short stature, ptosis, ophthalmoplegia and, in some cases, restrictive lung disease. Case presentation Hereby, we report on a four-generation Italian family with DA5. Our first proband was a newborn with prenatal suspicion of AMC. At birth, clinical findings were compatible with a DA diagnosis. Family history was positive for the mother with short stature, ophthalmoplegia, short neck, and contractures of the joints of distal extremities, and for three other relatives on the maternal side, including grandfather and great-grandmother, who all shared similar findings. Thus, we performed a next generation sequencing analysis (NGS) of the genes associated to AMC and of those involved in DA. The gain-of-function heterozygous mutation c.8181_8183delAGA (p.Glu2727del) of PIEZO2 was identified in the proband, and the same mutation was also found in the mother, confirming the autosomal dominant inheritance of the condition. Conclusions Our patients contribute to the current DA5 genomic database, and to a better characterization of the disease. Clinicians may have suspicion of a DA diagnosis based on suggestive (also prenatal) clinical findings, which must be then confirmed by NGS analysis. Since natural history varies widely among different DA disorders, detection of the underlying causal variant is essential for the identification of the exact subtype, and to its adequate management, which must rely on a multidisciplinary and individualized approach.

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“…A genetic diagnosis allows the families to feel less fragile, regardless of the benefit that it may have on the clinical management. NGS techniques allowed to provide early genetic counseling [45][46][47][48]. When promptly obtained, they may support and guide clinicians to the most appropriate clinical management and communicative approach, avoiding futile and/or disproportionate treatments [32], as well as further unnecessary separations between children and their parents [49].…”

Section: Discussionmentioning

confidence: 99%

Recommendations for neonatologists and pediatricians working in first level birthing centers on the first communication of genetic disease and malformation syndrome diagnosis: consensus issued by 6 Italian scientific societies and 4 parents’ associations

et al. 2021

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Background Genetic diseases are chronic conditions with relevant impact on the lives of patients and their families. In USA and Europe it is estimated a prevalence of 60 million affected subjects, 75% of whom are in developmental age. A significant number of newborns are admitted in the Neonatal Intensive Care Units (NICU) for reasons different from prematurity, although the prevalence of those with genetic diseases is unknown. It is, then, common for the neonatologist to start a diagnostic process on suspicion of a genetic disease or malformation syndrome, or to make and communicate these diagnoses. Many surveys showed that the degree of parental satisfaction with the methods of communication of diagnosis is low. Poor communication may have short and long-term negative effects on health and psychological and social development of the child and his family. We draw up recommendations on this issue, shared by 6 Italian Scientific Societies and 4 Parents’ Associations, aimed at making the neonatologist’s task easier at the difficult time of communication to parents of a genetic disease/malformation syndrome diagnosis for their child. Methods We used the method of the consensus paper. A multidisciplinary panel of experts was first established, based on the clinical and scientific sharing of the thematic area of present recommendations. They were suggested by the Boards of the six Scientific Societies that joined the initiative: Italian Societies of Pediatrics, Neonatology, Human Genetics, Perinatal Medicine, Obstetric and Gynecological Ultrasound and Biophysical Methodologies, and Pediatric Genetic Diseases and Congenital Disabilities. To obtain a deeper and global vision of the communication process, and to reach a better clinical management of patients and their families, representatives of four Parents’ Associations were also recruited: Italian Association of Down People, Cornelia de Lange National Volunteer Association, Italian Federation of Rare Diseases, and Williams Syndrome People Association. They worked from September 2019 to November 2020 to achieve a consensus on the recommendations for the communication of a new diagnosis of genetic disease. Results The consensus of experts drafted a final document defining the recommendations, for the neonatologist and/or the pediatrician working in a fist level birthing center, on the first communication of genetic disease or malformation syndrome diagnosis. Although there is no universal communication technique to make the informative process effective, we tried to identify a few relevant strategic principles that the neonatologist/pediatrician may use in the relationship with the family. We also summarized basic principles and significant aspects relating to the modalities of interaction with families in a table, in order to create an easy tool for the neonatologist to be applied in the daily care practice. We finally obtained an intersociety document, now published on the websites of the Scientific Societies involved. Conclusions The neonatologist/pediatrician is often the first to observe complex syndromic pictures, not always identified before birth, although today more frequently prenatally diagnosed. It is necessary for him to know the aspects of genetic diseases related to communication and bioethics, as well as the biological and clinical ones, which together outline the cornerstones of the multidisciplinary care of these patients. This consensus provide practical recommendations on how to make the first communication of a genetic disease /malformation syndrome diagnosis. The proposed goal is to make easier the informative process, and to implement the best practices in the relationship with the family. A better doctor-patient/family interaction may improve health outcomes of the child and his family, as well as reduce legal disputes with parents and the phenomenon of defensive medicine.

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Infant developmental profile of Crisponi syndrome due to compound heterozygosity for CRLF1 deletion

Cited by 30 publications

References 10 publications

Clinical and molecular genetic findings of Crisponi/cold‐induced sweating syndrome (CS/CISS) spectrum in patients from Turkey

Clinical and molecular genetic findings of Crisponi/cold‐induced sweating syndrome (CS/CISS) spectrum in patients from Turkey

Distal Arthrogryposis type 5 in an Italian family due to an autosomal dominant gain-of-function mutation of the PIEZO2 gene

Recommendations for neonatologists and pediatricians working in first level birthing centers on the first communication of genetic disease and malformation syndrome diagnosis: consensus issued by 6 Italian scientific societies and 4 parents’ associations

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