A de novo deletion of 20q11.2-q12 in a boy presenting with abnormal hands and feet, retinal dysplasia, and intractable feeding difficulty

Background. Geleophysic dysplasia is a rare multisystem disorder that principally affects the bones, joints, heart, and skin. This condition is inherited either in an autosomal dominant pattern due to FBN1 mutations or in an autosomal recessive pattern due to ADAMTSL2 mutations. Two patients with unaffected parents from unrelated families presented to their endocrinologist with severe short stature, resistant to growth hormone treatment. Routine endocrine tests did not reveal an underlying etiology. Exome sequencing was performed in each family. Our two patients, harboring de novo heterozygous FBN1 mutations p.Tyr1696Asp and p.Cys1748Ser, had common clinical symptoms such as severe short stature, characteristic facial features, short hands and feet, and limitation of joint movement. However, one patient had severe cardiac involvement whereas the other patient had tracheal stenosis requiring tracheostomy placement. Conclusions. Patients with severe dwarfism, skeletal anomalies, and other specific syndromic features (e.g., tracheal stenosis and cardiac valvulopathy) should undergo genetic testing to exclude acromelic dysplasia syndromes.

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CLINICAL GENETIC CHARACTERISTICS OF JANSEN-DE VRIES SYNDROME CAUSED BY HETEROZYGOUS MUTATIONS IN THE PPM1D GENE

PEDIATRIA Journal named after G N SPERANSKY ◽

10.24110/0031-403x-2021-100-1-277-282 ◽

2021 ◽

Vol 100 (1) ◽

pp. 277-282

Author(s):

N.A. Semenova ◽

◽

S.V. Dumova ◽

O.L. Chugunova ◽

I.N. Kotov ◽

...

Keyword(s):

De Novo ◽

Clinical Manifestations ◽

Speech Development ◽

Pathogenic Variant ◽

Neonatal Meningitis ◽

Clinical Genetic ◽

Genetic Characteristics ◽

First Child ◽

De Vries ◽

Hands And Feet

Jansen-de Vries syndrome is a rare hereditary autosomal dominant disease caused by pathogenic variants in the PPM1D gene. To date, 18 cases of this syndrome have been described in the world. In all cases, heterozygous mutations were identified that arose de novo in the last or penultimate exons of the gene, leading to protein truncation. All observed patients had muscle hypotonia, delayed motor and speech development, intellectual and behavioral disorders, an increased pain threshold, and a peculiar phenotype. Objective of the research: to reveal clinical genetic signs of new cases of a rare syndromic form and to identify additional clinical and laboratory features that characterize Jansen-de Vries syndrome. The article presents observations of two patients with Jansen-de Vries syndrome, first diagnosed in the Russian Federation. Children underwent routine laboratory and instrumental examinations, repeated consultations with a neurologist, geneticist, ophthalmologist, cardiologist and orthopedist. The diagnosis was made by full exome sequencing. A comparison of the identified cases with those described in the literature is performed. The observed girls from two unrelated families showed characteristic clinical manifestations, as in patients previously presented in the foreign literature: muscle hypotension, delayed motor and psycho-speech development, small hands and feet. Additionally, the first child had a prolonged course of neonatal meningitis and a low level of immunoglobulin A, the second had unilateral ptosis, congenital stridor. The de novo mutations found were confirmed by Sanger sequencing. A previously undescribed pathogenic variant c.1225del (p.Met409Ter) in the penultimate exon of the PPM1D gene was detected in the first child of 10 months. In the second child, a previously established pathogenic variant c.1270dupG (p.Glu424fs) was found in the last exon of this gene. Conclusion: the work presents the first domestic observations confirming the presence of characteristic clinical and genetic manifestations of the Jansen-de Vries syndrome. In addition, a previously undescribed pathogenic variant c.1225del (p.Met409Ter) was revealed in the penultimate exon of the PPM1D gene. In one of the observed children, features of humoral immunity were found, which may also be characteristic of this pathology.

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Prader-Willi Syndrome due to an Unbalanced de novo Translocation t(15;19)(q12;p13.3)

Cytogenetic and Genome Research ◽

10.1159/000452611 ◽

2016 ◽

Vol 150 (1) ◽

pp. 29-34 ◽

Cited By ~ 2

Author(s):

Vy Dang ◽

Abhilasha Surampalli ◽

Ann M. Manzardo ◽

Stephanie Youn ◽

Merlin G. Butler ◽

...

Keyword(s):

De Novo ◽

Chromosome Region ◽

Genetic Disorder ◽

Type I ◽

Prader Willi Syndrome ◽

Stk11 Gene ◽

Feeding Difficulties ◽

First Case ◽

Increased Risk ◽

Hands And Feet

Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic, and behavioral abnormalities. We report the first case of an unbalanced de novo reciprocal translocation of chromosomes 15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the PWS critical chromosome region. Our patient had several typical features of PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet, and food seeking, but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. High-resolution SNP microarray analysis identified an atypical PWS type I deletion in chromosome 15 involving the proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11q13 region, and GABRA5, GABRG3, and OCA2 genes were intact. No deletion of band 19p13.3 was detected; therefore, the patient was not at an increased risk of tumors from the Peutz-Jeghers syndrome associated with a deletion of the STK11 gene.

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Palmoplantar pustulosis – is there any progress in the treatment? / Palmoplantarna pustuloza – ima li pomaka u lečenju?

Serbian Journal of Dermatology and Venerology ◽

10.2478/v10249-011-0041-9 ◽

2011 ◽

Vol 3 (3) ◽

pp. 101-108

Author(s):

Đorđije Karadaglić ◽

Silvija Brkić

Keyword(s):

Nicotinic Acetylcholine Receptors ◽

De Novo ◽

Normal Population ◽

Specific Treatment ◽

Case Series ◽

Response To Treatment ◽

Cochrane Library ◽

Palmoplantar Pustulosis ◽

Line Therapy ◽

Hands And Feet

Abstract Despite, the fact that palmoplantar pustulosis is still widely known by this name, it is currently regarded as a disease distinct from psoriasis. The real cause is still unknown. Septic foci have been blamed, but their removal may not cure eruptions. A case series of de novo occurrence of palmoplantar pustulosis induced by tumor necrosis factor-alpha antagonist therapy has been reported. It has been shown that stress may be related to exacerbation of palmoplantar pustulosis. Some authors suggest that palmoplantar pustulosis is an autoimmune disease. In sera of patients with palmoplantar pustulosis circulating autoantibodies against nicotinic acetylcholine receptors were detected. The differences between palmoplantar pustulosis and pustular palmoplantar psoriasis are numerous. Genetic studies have failed to find any link between palmoplantar pustulosis and major genetic susceptibility locus for psoriasis vulgaris. Most patients with palmoplantar pustulosis have no evidence of psoriasis elsewhere. Histologically, it closely resembles psoriasis. However, accumulation of neutrophils just beneath the corneal layer, finding known as Munro’s microabscess, and dilation of capillaries in the papillary dermis are lacking. Approximately 90% of patients are women. A significantly higher prevalence of smokers was found in the group with palmoplantar pustulosis than in the normal population and a particularly strong association was confirmed between smoking and pustular lesions in patients with psoriasis, OR=5.3 (2.1-13.0). Nevertheless, according to a recent review from the Cochrane Library, there is no evidence that smoking cessation improves the condition once it has developed. Topical corticosteroids under occlusion are the first-line therapy. Prolonged therapy is needed on a second or third-day basis, in order to sustain the obtained effects. Oral retinoids in combination with oral PUVA are the best second-line therapy. No difference in the efficacy between etretinate and acitretin was found. The disadvantage of systemic retinoid therapy is its teratogenicity. Oral PUVA is effective and the response is enhanced by combination with retinoids. There is an established increased efficacy of a combination of retinoids with PUVA therapy over each treatment modallity when used alone. Liarozole may be an effective and well-tolerated therapy, but side effects are like in retinoids. The advantage over acitretin is that raised levels of retinoic acid fall to normal within a few days after cessation of therapy. Significant improvement, but no complete clearance, occurs in most patients treated with low dose cyclosporine. Before starting the treatment, it is necessary to consider: patient’s individual factors, since many patients have already received some previous treatment; specific treatment factors such as formulation, way of administration, dose, different drug combinations; regimens and periods of treatment; site of involvement, due to differences between hands and feet in the probability of response to treatment.

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The smallest de novo deletion of 20q11.21-q11.23 in a girl with feeding problems, retinal dysplasia, and skeletal abnormalities

American Journal of Medical Genetics Part A ◽

10.1002/ajmg.a.36394 ◽

2014 ◽

Vol 164 (4) ◽

pp. 1056-1061 ◽

Cited By ~ 7

Author(s):

Renata Posmyk ◽

Ryszard Leśniewicz ◽

Magdalena Gogiel ◽

Monika Chorąży ◽

Alina Bakunowicz-Łazarczyk ◽

...

Keyword(s):

De Novo ◽

Feeding Problems ◽

Skeletal Abnormalities ◽

Retinal Dysplasia

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Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review

BMC Medical Genomics ◽

10.1186/s12920-020-00802-0 ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Shan Li ◽

Ke-wang Xi ◽

Ting Liu ◽

Ying Zhang ◽

Meng Zhang ◽

...

Keyword(s):

Clinical Features ◽

De Novo ◽

Genetic Disorder ◽

Deletion Syndrome ◽

Facial Dysmorphism ◽

Germline Mosaicism ◽

Third Generation Sequencing ◽

Neurological Features ◽

Hands And Feet ◽

Abnormal Behaviors

Abstract Background Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome. Case presentation We describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region. Conclusions Our case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.

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Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations

Journal of Child Neurology ◽

10.1177/0883073816674095 ◽

2016 ◽

Vol 32 (2) ◽

pp. 237-242 ◽

Cited By ~ 12

Author(s):

Jung Min Ko ◽

Jae So Cho ◽

Yongjin Yoo ◽

Jieun Seo ◽

Murim Choi ◽

...

Keyword(s):

De Novo ◽

Genetic Disorder ◽

Ductus Arteriosus ◽

Developmental Dysplasia ◽

Facial Dysmorphism ◽

Sequencing Analysis ◽

Self Mutilation ◽

Small Hands ◽

Hands And Feet ◽

Dysplasia Of The Hip

Wiedemann-Steiner syndrome is a rare genetic disorder characterized by short stature, hairy elbows, facial dysmorphism, and developmental delay. It can also be accompanied by musculoskeletal anomalies such as muscular hypotonia and small hands and feet. Mutations in the KMT2A gene have only recently been identified as the cause of Wiedemann-Steiner syndrome; therefore, only 16 patients from 15 families have been described, and new phenotypic features continue to be added. In this report, we describe 2 newly identified patients with Wiedemann-Steiner syndrome who presented with variable severity. One girl exhibited developmental dysplasia of the hip and fibromatosis colli accompanied by other clinical features, including facial dysmorphism, hypertrichosis, patent ductus arteriosus, growth retardation, and borderline intellectual disability. The other patient, a boy, showed severe developmental retardation with automatic self-mutilation, facial dysmorphism, and hypertrichosis at a later age. Exome sequencing analysis of these patients and their parents revealed a de novo nonsense mutation, p.Gln1978*, of KMT2A in the former, and a missense mutation, p.Gly1168Asp, in the latter, which molecularly confirmed the diagnosis of Wiedemann-Steiner syndrome.

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Hearing assessment in a rare case of Hajdu Cheney syndrome

International Journal of Otorhinolaryngology and Head and Neck Surgery ◽

10.18203/issn.2454-5929.ijohns20174352 ◽

2017 ◽

Vol 3 (4) ◽

pp. 1140

Author(s):

Priyanka . ◽

Shiffali . ◽

Manpreet Singh ◽

Jagdeepak Singh

Keyword(s):

Hearing Loss ◽

De Novo ◽

Bone Fractures ◽

Heart Defects ◽

Joint Hypermobility ◽

De Novo Mutation ◽

Body Hair ◽

Hearing Assessment ◽

Characteristic Features ◽

Hands And Feet

<p class="abstract"><span lang="EN-IN">Hajdu Cheney syndrome is extremely rare autosomal dominant congenital disorder of connective tissue. It may occur due to spontaneous de novo mutation and mutation in NOTCH-2 gene identified recently. Most characteristic features include aero-osteolysis involving phalanges of both hands and feet, osteoporosis, deformities of skull, mandible, spine and other bones, kyphoscoliosis and bone fractures. Rarely in some affected individuals, it causes joint hypermobility, dental problems, hearing loss, heart defects, kidney abnormality like polycystic kidneys, excess body hair and recurrent infections in childhood. It affects many parts of body particularly bones. Treatment is symptomatic. In this case report, we present a case of 14 years male child with features of Hajdu Cheney syndrome with genetic predisposition. Patient presented to ENT clinic with complaint of hearing loss.</span></p>

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Insights into the pathogenesis and treatment of split/hand foot malformation (cleft hand/foot)

Journal of Hand Surgery (European Volume) ◽

10.1177/1753193418807375 ◽

2018 ◽

Vol 44 (1) ◽

pp. 80-87

Author(s):

Stéphane Guero ◽

Muriel Holder-Espinasse

Keyword(s):

De Novo ◽

Autosomal Recessive Inheritance ◽

De Novo Mutation ◽

Incomplete Penetrance ◽

Term Outcome ◽

Long Term Outcome ◽

Sporadic Cases ◽

Cleft Hand ◽

Hands And Feet ◽

A Minor

Cleft hand or split hand foot malformation is a sequence of phenotypes, from a minor shortening of the central digit to a complete absence of the third ray and in the most severe cases, absence of two, three or four rays. It is a rare but spectacular presentation usually involving both hands and feet. Inheritance is mostly autosomal dominant but sporadic cases without family history are also reported, resulting from a de novo mutation/deletion/duplication. Intra-familial clinical variability is the rule, with incomplete penetrance. X-linked or autosomal recessive inheritance has also been described. To date, seven subgroups of split hand foot malformation have been identified and seven loci are currently known. Anatomical records have enhanced our knowledge of this group of disorders of the hands and feet and allowed us to improve surgical procedures and long-term outcome.

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