Typical Dysmorphic Features Research Articles

Beyond the known phenotype of sotos syndrome: a 31-individuals cohort study.

Sotos Syndrome (SS, OMIM#117550) is a heterogeneous genetic condition, recognized by three main clinical features present in most cases: overgrowth with macrocephaly, typical facial appearance and different degrees of intellectual disability. Three different types are described caused by variants or deletions/duplications in NSD1, NFIX and APC2 genes. We aimed to describe a cohort of pediatric patients reporting the typical and unexpected findings in order to expand the phenotype of this syndrome and trying to find genotype-phenotype correlations. In our referral center, we collected and analyzed clinical and genetic data of 31-patients cohort diagnosed with SS. All of them presented with overgrowth, typical dysmorphic features and different degree of developmental delay. Although structural cardiac defects have been reported in SS, non-structural diseases such as pericarditis were outstanding in our cohort. Moreover, we described here novel oncological malignancies not previously linked to SS such as splenic hamartoma, retinal melanocytoma and acute lymphocytic leukemia. Finally, five patients suffered from recurrent onychocryptosis that required surgical procedures, as an unreported prevalent medical condition. This is the first study focusing on multiple atypical symptoms in SS at the time that revisits the spectrum of clinical and molecular basis of this heterogeneous entity trying to unravel a genotype-phenotype correlation.

New insights on partial trisomy 3q syndrome: de novo 3q27.1-q29 duplication in a newborn with pre and postnatal overgrowth and assisted reproductive conception

BackgroundDuplications of the long arm of chromosome 3 are rare, and associated to a well-defined contiguous gene syndrome known as partial trisomy 3q syndrome. It has been first described in 1966 by Falek et al., and since then around 100 patients have been reported. Clinical manifestations include characteristic facial dysmorphic features, microcephaly, hirsutism, congenital heart disease, genitourinary anomalies, hand and feet abnormalities, growth disturbances and intellectual disability. Most of cases are due to unbalanced translocations, inherited from a parent carrying a balanced aberration (reciprocal translocation or inversion), and rarely the genomic anomaly arises de novo. Very few studies report on the prenatal identification of such rearrangements.Case presentationHereby, we report on a newborn with a rare pure duplication of the long arm of chromosome 3. Noninvasive prenatal test (cell free fetal DNA analysis on maternal blood), performed for advanced parental age and use of assisted reproductive technique, evidenced a partial 3q trisomy. Then, invasive cytogenetic (standard and molecular) investigations, carried out through amniocentesis, confirmed and defined a 3q27.1-q29 duplication spanning 10.9 Mb, and including about 80 genes. Our patient showed clinical findings (typical facial dysmorphic features, esotropia, short neck, atrial septal defect, hepatomegaly, mild motor delay) compatible with partial trisomy 3q syndrome diagnosis, in addition to pre- and postnatal overgrowth.ConclusionsAdvanced parental age increases the probability of chromosomal and/or genomic anomalies, while ART that of epigenomic defects. Both conditions, thus, deserve more careful prenatal monitoring and screening/diagnostic investigations. Among the latter, cell free fetal DNA testing can detect large segmental aneuploidies, along with chromosomal abnormalities. It identified in our patient a wide 3q rearrangement, then confirmed and defined through invasive molecular cytogenetic analysis. Neonatologists and pediatricians must be aware of the potential risks associated to duplication syndromes. Therefore, they should offer to affected subjects an adequate management and early and careful follow-up. These may be able to guarantee to patients satisfactory growth and development profiles, prevent and/or limit neurodevelopmental disorders, and timely recognition of complications.

Two South African patients with PGAP3-related Mabry syndrome with unusually low alkaline phosphatase levels


 
 
 
 Hyperphosphatasia with mental retardation syndrome (HPMRS), also known as Mabry syndrome, is an autosomal recessive disease that is associated with inherited glycosylphosphatidylinositol (GPI) deficiencies. This genetically heterogeneous disorder can be caused by variants in seven genes that encode molecules of the glycosylphosphatidylinositol (GPI)-anchor biosynthesis pathway, namely PIGL, PIGO, PIGV, PIGW, PIGY, PGAP2 and PGAP3. Recently, a pathogenic variant in PGAP3 was identified in 3 unrelated South African patients with HMPRS. Here, two further patients with the exact variant in PGAP3 are described. Classically, HMPRS is associated with elevated alkaline phosphatase (ALP) levels. Interestingly, these two patients had unusually low ALP levels at initial presentation. This is an important observation, as the ALP level is often used as a screening test to decide whether to proceed to confirmatory genetic testing. These patients illustrate that in PGAP3-related Mabry syndrome, ALP levels can be low, albeit a rare finding. Hence, a high suspicion for the disorder should be maintained in patients with typical facial dysmorphic features and severe neurodevelopmental delay, even in the absence of elevated ALP.
 
 
 

Identification of a novel pathogenic TBCK variant in a Chinese patient with infantile hypotonia with psychomotor retardation and characteristic facies type 3 (IHPRF3): a case report

BackgroundInfantile hypotonia with psychomotor retardation and characteristic facies type 3(IHPRF3) (OMIM #616,900) is an autosomal recessive disorder caused by biallelic pathogenic variants of the TBCK gene, and to date, this disease was reported rather limitedly in number and all described cases were Caucasians.Case presentationThis paper reported the clinical and genetic features of a Chinese patient with IHPRF3. The patient was a 15-month-old male with global developmental delay, profound hypotonia, and typical facial dysmorphic features including mildly coarse facial appearance, hypertelorism, tented upper lip, exaggerated Cupid’s bow, macroglossia and arched eyebrows. Magnetic Resonance Imaging (MRI) analysis of the brain revealed slightly widened bilateral ventricles and subarachnoid space. On genetic analysis, the patient was homozygous for a novel TBCK variant c.247C > T(p.Arg83Ter). The parents were both carriers without any positive symptoms or signs. With an extremely low frequency (0.0000082) in Exome Aggregation Consortium, the variant has not been reported in any other databases or official literatures, and was diagnosed to be pathogenic according to the American College of Medical Genetics and Genomics(ACMG) standards and guidelines. Neurorehabilitation training did not work well and the long-term prognosis remained to be observed.ConclusionsThis study reported the clinical and molecular features of the first non-Caucasian patient with IHPRF3 arising from a novel homozygous TBCK mutation, which provided a novel molecular marker for the definite diagnosis of IHPRF3 patients and for its genetic counseling and prenatal diagnosis in the affected families.

Hypoparathyroidism-Retardation-Dysmorphism Syndrome due to a Variant in the Tubulin-Specific Chaperone E Gene as a Cause of Combined Immune Deficiency.

BackgroundHypoparathyroidism-retardation-dysmorphism (HRD) syndrome is a disease composed of hypoparathyroidism, growth retardation, severe developmental delay, and typical dysmorphic features caused by the tubulin-specific chaperone E gene variant. Many patients succumb in infancy to HRD due to overwhelming infections mainly caused by Pneumococcus spp. Knowledge related to the immune system in these patients is scarce.PurposeTo define the immune phenotype of a cohort of HRD patients including their cellular, humoral, and neutrophil functions.MethodsThe study included HRD patients followed at Soroka University Medical Center. Clinical and immunological data were obtained, including immunoglobulin concentrations, specific antibody titers, lymphocyte subpopulations, lymphocyte proliferation, and neutrophil functions.ResultsNine patients (5 females and 4 males) were enrolled, aged 6 months to 15 years. All received amoxicillin prophylaxis as part of a routine established previously. Three patients had bacteremia with Klebsiella, Shigella spp., and Candida. Three patients had confirmed coronavirus disease 19 (COVID-19), and two of them died from this infection. All patients had normal blood counts. Patients showed high total IgA and IgE levels, low anti-pneumococcal antibodies in spite of a routine vaccination schedule, and reduced frequency of naive B cells with increased frequency of CD21lowCD27- B cells. All patients had abnormal T-cell population distributions, including reduced terminally differentiated effector memory CD8, inverted CD4/CD8 ratios, and impaired phytohemagglutinin (PHA)-induced lymphocyte proliferation. Neutrophil superoxide production and chemotaxis were normal in all patients tested.ConclusionHRD is a combined immunodeficiency disease with syndromic features, manifesting in severe invasive bacterial and viral infections.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10875-022-01380-9.

Lobster Claw Hand Deformity - Cornelia de Lange Syndrome

Background: Cornelia de Lange syndrome is a genetic syndrome characterized by intellectual disability, facial features with synorphrys or fused eyebrows, upper limb anomalies and atypical growth. It is caused by spontaneous mutations in genes responsible for structural or regulatory function of cohesin complex.
 Report: We present two newborns cases admitted to our NICU with characteristic dysmorphic features of microcephaly, ectrodactyly and thick eyebrows. One baby also had associated congenital heart defect and sensorineural hearing loss. Both babies are under followup with developmental early intervention programs. Parents were offered genetic counselling for future pregnancies.
 Conclusion: Cornelia de Lange is predominantly a clinical diagnosis by identifying typical dysmorphic features. Labelling a syndromic diagnosis helps to provide genetic counselling to the parents, identify associated co-morbidities at earlier stages and improve the quality of living of such children.

From Wolf-Hirschhorn syndrome to NSD2 haploinsufficiency: a shifting paradigm through the description of a new case and a review of the literature

BackgroundWolf-Hirschhorn syndrome (WHS) is a well-defined disorder, whose core phenotype encompasses growth restriction, facial gestalt, intellectual disability and seizures. Nevertheless, great phenotypic variability exists due to the variable extent of the responsible 4p deletion. In addition, exome sequencing analyses, recently identified two genes, namely NSD2 and NELFA, whose loss-of-function variants contribute to a clinical spectrum consistent with atypical or partial WHS.The observation of patients exhibiting clinical features resembling WHS, with only mild developmental delay and without the typical dysmorphic features, carrying microdeletions sparing NSD2, has lead to the hypothesis that NSD2 is responsible for the intellectual disability and the facial gestalt of WHS. While presenting some of the typical findings of WHS (intellectual disability, facial gestalt, microcephaly, growth restriction and congenital heart defects), NSD2-deleted children tend to display a milder spectrum of skeletal abnormalities, usually consisting of clinodactyly, and do not exhibit seizures.We describe the clinical picture of a child with WHS due to a de novo mutation of NSD2 and discuss the clinical and diagnostic implications.Case presentationA 6-year-old boy was evaluated for a history of intrauterine growth restriction, low birth weight, neonatal hypotonia, and psychomotor delay. No episodes of seizure were reported. At physical examination, he displayed marphanoid habitus, muscle hypotrophy and facial dysmorphisms consisting in high frontal hairline, upslanting palpebral fissures and full lips with bifid ugula. Cryptorchidism, shawl scrotum, mild clinodactyly of the right little finger and bilateral syndactyly of the II and III toes with sandal gap were also noted. The radiographic essay demonstrated delayed bone age and echocardiography showed mild mitral prolapse. Whole genome sequencing analysis revealed a heterozygous de novo variant of NSD2 (c.2523delG).ConclusionsFull WHS phenotype likely arises from the cumulative effect of the combined haploinsufficiency of several causative genes mapping within the 4p16.3 region, as a contiguous genes syndrome, with slightly different phenotypes depending on the specific genes involved in the deletion.When evaluating children with pictures resembling WHS, in absence of seizures, clinicians should consider this differential diagnosis.

Prolidase deficiency, a rare inborn error of immunity, clinical phenotypes, immunological features, and proposed treatments in twins

BackgroundProlidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in the PEPD gene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. PD is categorized as a metabolic disease, but also as an inborn error of immunity. PD presents with a range of findings including dysmorphic features, intellectual disabilities, recurrent infections, intractable skin ulceration, autoimmunity, and splenomegaly. Despite symptoms of immune dysregulation, only very limited immunologic assessments have been reported and standard therapies for PD have not been described. We report twin females with PD, including comprehensive immunologic profiles and treatment modalities used.Case presentationPatient 1 had recurrent infections in childhood. At age 13, she presented with telangiectasia, followed by painful, refractory skin ulcerations on her lower limbs, where skin biopsy excluded vasculitis. She had typical dysmorphic features of PD. Next-generation sequencing revealed pathogenic compound heterozygous mutations (premature stop codons) in the PEPD gene. Patient 2 had the same mutations, typical PD facial features, atopy, and telangiectasias, but no skin ulceration. Both patients had imidodipeptiduria. Lymphocyte subset analysis revealed low-normal frequency of Treg cells and decreased frequency of expression of the checkpoint molecule CTLA-4 in CD4+ TEM cells. Analysis of Th1, Th2, and Th17 profiles revealed increased inflammatory IL-17+ CD8+ TEM cells in both patients and overexpression of the activation marker HLA-DR on CD4+ TEM cells, reflecting a highly activated proinflammatory state. Neither PD patient had specific antibody deficiencies despite low CD4+CXCR5+ Tfh cells and low class-switched memory B cells. Plasma IL-18 levels were exceptionally high.ConclusionsImmunologic abnormalities including skewed frequencies of activated inflammatory CD4+ and CD8+ TEM cells, decreased CTLA-4 expression, and defects in memory B cells may be a feature of immune dysregulation associated with PD; however, a larger sample size is required to validate these findings. The high IL-18 plasma levels suggest underlying autoinflammatory processes.

Clinical expert case with a combination of the Saul–Wilson and Rubinstein–Taybi syndromes

SaulWilson syndrome, like RubinsteinTaybi syndrome, is classified as a rare genetic disease according to modern classification. So, to date, there are descriptions of 16 patients from different countries in literary sources.
 The SaulWilson syndrome is characterized by a combination of nanism, pathology of long tubular bones, the spine and the organ of vision, typical dysmorphic facial features and radiological data; RubinsteinTaybi syndrome has various skeletal defects (low height, dilation of the phalanges of the fingers, polydactyly on the legs, deformities of the face and skull, high arched palate, changes in the shape and position of the auricles, dilated phalanges of the fingers, lordosis, kyphosis, scoliosis), strabismus, anomalies refraction, disorders of internal organs, disorders of intellectual and physical development.
 The article presents a complex clinical and expert case with a combination of two genetic diseases ― SaulWilson and RubinsteinTaybi syndromes, typical manifestations of which were visible craniofacial dysmorphia, changes in the musculoskeletal system in the form of progressive bilateral coxarthrosis, instability of the thoracic spine, deformities of the feet, accompanied by pronounced disorders of neuromuscular, skeletal and statodynamic functions. The multi-system lesion of the body caused difficulties for specialists during the medical and social examination. These nosological forms are absent in the current classifications and criteria for establishing disability, and therefore the quantitative assessment of persistent functional disorders was carried out individually ― according to the degree of severity of impaired functions, their combination and influence on each other.
 The use of modern diagnostic methods, including genetic studies, in hereditary diseases allows to establish a diagnosis at an early stage, to determine the tactics of managing children in order to ensure timely pathogenetic treatment, including surgical, prevention of the development of severe complications, functional disorders. The successes of medicine can not only significantly improve the quality of life of this category of children, but also increase their life expectancy. Since in most cases hereditary diseases involving the musculoskeletal system are accompanied by persistent disorders of the bodys functions and lead to disability, classifications and criteria for establishing disability should include a quantitative assessment of the degree of impaired functions in congenital anomalies and hereditary diseases.

Identification of two novel homozygous mutations in ERCC8 gene in two unrelated consanguineous families with Cockayne syndrome from Iran

BackgroundCockayne syndrome (CS) is a rare autosomal recessive disorder with characteristic multisystem involvement including pre- or post-natal growth failure, progressive neurological dysfunction, psychomotor retardation, cerebral atrophy, microcephaly and mental retardation, due to mutations in either the ERCC8/CSA or ERCC6/CSB gene. MethodWe present two Iranian patients with remarkable growth failure, developmental delay, microcephaly, severe speech delay, vision problem, sun sensitivity, hearing loss, dental anomalies, unstable gait, mild contractures in knees, kyphosis and spasticity in lower limbs, balance disorders and typical dysmorphic features including long nose, aged face, large ears and sunken eyes.Clinical evaluation, magnetic resonance imaging, Peripheral blood karyotype, Multiplex ligation-dependent probe amplification (MLPA), and whole-exome sequencing were used to characterize etiology in two patients from two unrelated consanguineous families of Iranian descent with Cockayne syndrome. ResultsWe detected two novel pathogenic mutations in two unrelated families, a homozygous duplication mutation (c.317_320dupAGTG, p.Trp107Ter) and a splicing variant (c.481 + 1G > A) in ERCC8 gene. ConclusionWES results together with the characteristic clinical manifestations of Cockayne syndrome, provided an accurate diagnosis for two patients. Also, our study identified two novel variants in Iranian families.

A Novel Multi-Exon Deletion of PACS1 in a Three-Generation Pedigree: Supplements to PACS1 Neurodevelopmental Disorder Spectrum.

PACS1 neurodevelopmental disorder (PACS1-NDD) is a category of rare disorder characterized by intellectual disability, speech delay, dysmorphic facial features, and developmental delay. Other various physical abnormalities of PACS1-NDD might involve all organs and systems. Notably, there were only two unique missense mutations [c.607C > T (p.Arg203Trp) and c.608G > A (p.Arg203Gln)] in PACS1 that had been identified as pathogenic variants for PACS1-NDD or Schuurs-Hoeijmakers syndrome (SHMS). Previous reports suggested that these common missense variants were likely to act through dominant-negative or gain-of-function effects manner. It is still uncertain whether the intragenic deletion or duplication in PACS1 will be disease-causing. By using whole-exome sequencing, we first identified a novel heterozygous multi-exon deletion covering exons 12–24 in PACS1 (NM_018026) in four individuals (two brothers and their father and grandfather) in a three-generation family. The younger brother was referred to our center prenatally and was evaluated before and after the birth. Unlike SHMS, no typical dysmorphic facial features, intellectual problems, and structural brain anomalies were observed among these four individuals. The brothers showed a mild hypermyotonia of their extremities at the age of 3 months old and recovered over time. Mild speech and cognitive delay were also noticed in the two brothers at the age of 13 and 27 months old, respectively. However, their father and grandfather showed normal language and cognitive competence. This study might supplement the spectrum of PACS1-NDD and demonstrates that the loss of function variation in PACS1 displays no contributions to the typical SHMS which is caused by the recurrent c.607C > T (p.Arg203Trp) variant.

From cataract to syndrome diagnosis: Revaluation of Warburg-Micro syndrome Type 1 patients.

Warburg-Micro syndrome (WARBM) is a rare autosomal recessively inherited neuro-ophthalmologic syndrome. Although WARBM shows genetic heterogeneity, the pathogenic variants in RAB3GAP1 were the most common cause of WARBM. In this study, we aimed to evaluate the detailed clinical and dysmorphic features of seven WARBM1 patients and overview the variant spectrum of RAB3GAP1 in comparison with the literature who were referred due to congenital cataracts. A previously reported homozygous variant (c.2187_2188delGAinsCT) was identified in three of these patients, while the other four had three novel variants (c.251_258delAGAA, c.2606+1G>A, and c.2861_2862dupGC). Congenital cataract and corpus callosum hypo/agenesia are pathognomonic for WARBM, which could be distinguished from other similar syndromes with additional typical dysmorphic facial features. Although there is no known phenotype and genotype correlation in any type of WARBM, RAB3GAP1 gene analysis should be previously requested as the first step of genetic diagnosis in clinically suspicious patients when it is not possible to request a multi-gene panel.

Hypersociability associated with developmental delay, macrocephaly and facial dysmorphism points to CHD3 mutations

CHD3-related syndrome, also known as Snijders Blok-Campeau syndrome, is a rare developmental disorder described in 2018, caused by de novo pathogenic variants in the CHD3 gene. This syndrome is characterized by global developmental delay, speech delay, intellectual disability, hypotonia and behavioral disorders including autism spectrum disorder (ASD). Typical dysmorphic features include macrocephaly, hypertelorism, enophthalmia, sparse eyebrows, bulging forehead, midface hypoplasia, prominent nose and pointed chin. To our knowledge, there have been no other clinical descriptions of patients since the initial publication.We report the clinical description of a 21-year-old patient harboring a pathogenic de novo variant in CHD3. We reviewed the clinical features of the 35 previously reported patients. Main features were severe intellectual disability, dysmorphic facies, macrocephaly, cryptorchidism, pectus carinatum, severe ophthalmologic abnormalities and behavioral disorders including ASD, and a frank happy demeanor. Hypersociability, which was a noticeable clinical feature in our case, despite ASD, is an uncommon behavioral feature in syndromic intellectual disabilities. Our report supports hypersociability as a suggestive feature of CHD3-related syndrome along with developmental delay, macrocephaly and a dysmorphic facies.

Novel GJA1/Cx43 Variant Associated With Oculo-Dento-Digital Dysplasia Syndrome: Clinical Phenotype and Cellular Mechanisms

Oculodentodigital dysplasia syndrome is associated with numerous pathogenic variants in GJA1, the gene encoding connexin43 gap junction protein. A novel in-frame deletion (p.Lys134del) was found in our clinic. The patient showed all the typical dysmorphic features of the syndrome. The functional consequences of this variant were also studied in an in vitro system. Cells expressed significantly less number of gap junction plaques with a great number of them retained intracellularly.

Clinical and genetic characteristics and orthopedic manifestations of the Saul–Wilson syndrome in two Russian patients

Background. SaulWilson syndrome (SWS, microcephalic osteodysplastic dysplasia) is a rare genetic variant of skeletal dysplasia and is determined based on the modern classification for thin bone dysplasias. To date, 16 patients with SWS from different countries have been identified.
 Clinical cases. We presented the first description of the clinical and genetic characteristics of two Russian patients with SWS and compared them with published data. The main clinical manifestations of SWS are characterized by a combination of nanism and pathology of long tubular bones, spine, and eyes. Changes in the phenotype of patients in different age groups were analyzed.
 Discussion. In the analysis of the clinical manifestations of the observed patients and patients described in the literature, typical dysmorphic features of the face and radiographic data help in the diagnosis of SWS upon clinical examination. In the majority of the described patients, the nucleotide substitution c.1546GA is the major mutation in the gene responsible for SWS, which leads to the replacement of the amino acid Gly516Arg in the protein molecule.
 Conclusion. Based on the identified specific features of the phenotype of patients with SWS and the presence of a major mutation in the COG4 gene, a priority analysis of gene mutations is necessary. Orthopedic manifestations of SWS can lead to life-threatening conditions (cervical spine instability) and motor limitations (progressive osteoarthritis) and thus should be monitored dynamically.

A rare cause of syndromic short stature: 3M syndrome in three families.

3M syndrome is a rare autosomal recessive genetic disorder characterized by severe growth retardation, dysmorphic facial features, skeletal dysplasia, and normal intelligence. Variants in CUL7, OBSL1, and CCDC8 genes have been reported to be responsible for this syndrome. In this study, the clinical and molecular findings of four 3M syndrome cases from three families are presented. All cases had growth retardation, relative macrocephaly, and typical dysmorphic facial features. Their neurological developments were normal. Sequencing of CUL7, OBSL1, and CCDC8 genes revealed two different novel homozygous variants in CUL7 in Families 1 and 3 and a previously reported homozygous pathogenic variant in OBSL1 in Family 2. In conclusion, a comprehensive dysmorphological evaluation should be obtained in individuals presenting with short stature and in such individuals with typical facial and skeletal findings, 3M syndrome should be considered. Our report expands the genotype of 3M syndrome and emphasizes the importance of thorough physical and dysmorphological examination.

Phenotypic expansion of KMT2D-related disorder: Beyond Kabuki syndrome.

Pathogenic variants in KMT2D, which encodes lysine specific methyltransferase 2D, cause autosomal dominant Kabuki syndrome, associated with distinctive dysmorphic features including arched eyebrows, long palpebral fissures with eversion of the lower lid, large protuberant ears, and fetal finger pads. Most disease-causing variants identified to date are putative loss-of-function alleles, although 15-20% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo KMT2D missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. These individuals also lack the typical dysmorphic facial features found in Kabuki syndrome. Two of the four patients had severe interstitial lung disease. All of these variants cluster within a 40-amino-acid region of the protein that is located just N-terminal of an annotated coiled coil domain. These findings significantly expand the phenotypic spectrum of features associated with variants in KMT2D beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients.

Incontinence and psychological symptoms in Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMD) is a congenital syndrome caused by a deletion on chromosome 22q13.3. About 600 cases have been identified worldwide. PMD is characterized by neonatal hypotonia, moderate/severe intellectual impairment, impaired expressive language, and typical dysmorphic features. Psychological symptoms as hyperactivity, attention problems, restlessness, and stereotyped-repetitive behavior were reported. The aim of the study was to assess incontinence and associated psychological problems in PMD. Forty-one individuals with PMD were recruited through a German support group (48.8% male; mean age 13.4 years; range, 4-55 years). Parents or caregivers completed the developmental behavior checklist (DBC), as well as the parental questionnaire: enuresis/urinary incontinence, including six questions on adaptive toileting skills. Rates of nocturnal enuresis (NE), daytime urinary incontinence, and fecal incontinence were 86%, 73%, and 79%. Rates were similar in all age groups (children, teens, adults). Constipation was present in 19%. Forty-two percent of the sample had a clinically relevant DBC score, with adults more affected than teens. Persons with NE had significantly higher "anxiety/depression" subscale scores. Toileting skills were more developed in adults than in children. Sixty-eight percent had further physical disabilities. Incontinence rates in PMD are high in all age groups. However, persons with PMD can improve their toilet skills. Therefore, the assessment and treatment of incontinence in persons with PMD is recommended. Constipation does not seem to be a major problem in PMD. Due to the high prevalence rates of somatic conditions, an assessment for organic and functional incontinence is recommended.

Long-term trends in the prevalence of congenital heart defects in patients with Down syndrome in southern Poland

IntroductionDown syndrome is one of the most common chromosomal abnormalities in humans. Patients have typical dysmorphic features and various congenital malformations. Congenital heart defects were reported as the most common of the latter, occurring in approximately 50% of the cases.The aimWe aimed to analyse the long-term trends in the prevalence of Down syndrome and related heart defects in the population of southern Poland (Krakow region)Material and methodsWe analysed 500 consecutive patients with Down syndrome who were born from 2006 through 2017 and were diagnosed at the Department of Medical Genetics, Jagiellonian University. Next, we compared our results with the data obtained in previous regional studies.ResultsThe prevalence of Down syndrome in the assessed period was 1.65 per 1,000 live births and was similar to the historical prevalence in our region. Cardiac malformations were detected in 57.6% of the patients and the common atrioventricular canal (CAVC) was the most frequent anomaly (35.1%). However, detailed analysis of the frequency of severe heart defects that usually require prompt surgical treatment in the course of infancy revealed that the percentage of CAVC has been significantly lower in recent years (p=0.033).ConclusionsThe prevalence of Down syndrome and the overall frequency of congenital heart defects have not significantly changed in recent years. However, the frequency of CAVC has decreased, which could be related to the technical progress in prenatal detection of this severe anomaly, and to the subsequent elective terminations of affected pregnancies. Further population studies are required to confirm the presence of this trend and elucidate its background.

Partial trisomy 15: a rare occurrence

Partial trisomy 15q is a very rare entity and most of them are characterized by duplication of regions 15q21-15q26.3. This duplication is frequently associated with deletions in another chromosome resulting in unbalanced translocations. Authors report here, a rare case of partial trisomy 15, with breakpoints between 15q11.1 to q23, probably the first reported case with these breakpoints. Irrespective of the breakpoints, the phenotypic features are consistent in all affected cases and predominantly consist of craniofacial anomalies. In addition, finger abnormalities, very short neck, skeletal malformations and congenital heart disease may be present. Our neonate had typical dysmorphic features of arachnocamptodactyly, narrow face, large prominent, nose with broad nasal bridge, long philtrum, pointed chin, short neck, and low set deformed ears. Neonates’ cytogenetic analysis revealed additional chromosomal material on the long arm of the chromosome 15 from q11.1 to q23.1, which was suggestive of partial trisomy of chromosome 15. Most cases reported have had a stormy clinical course, however, our proband had only mild respiratory distress at birth and she was discharged in a few days.