SOFT syndrome with kohlschutter-Tonz syndrome.

We report a 2.2 year-old-boy, born of consanguineous marriage, referred for short stature, with history of neonatal death and skeletal deformities in his older sibling. Rhizo-mesomelic dwarfism was detected antenatally. Within 24 hours of birth, he developed multiple seizures. Examination revealed severe short stature, dolichocephaly, broad forehead, deep set eyes, low set ears, bulbous nose, small, irregular teeth, pointed chin, and triangular facies. He had rhizomelic shortening, stubby fingers, pes planus, and scanty hair. Neurological evaluation revealed ataxia, hypotonia, and global developmental delay. Skeletal survey radiograph revealed shallow acetabuli, short femurs and humerus, short, broad metacarpals and short cone-shaped phalanges with cupping of phalangeal bases. Clinical exome analysis revealed homozygous mutations involving the POC1A gene and the SLC13A5 gene responsible for SOFT syndrome and Kohlschutter-Tonz syndrome respectively, which were inherited from the parents. Both these syndromes are extremely rare, and their co-occurrence is being reported for the first time.

Growth reference charts for children with hypochondroplasia.

Hypochondroplasia (HCH) is a rare skeletal dysplasia causing mild short stature. There is a paucity of growth reference charts for this population. Anthropometric data were collected to generate height, weight, and head circumference (HC) growth reference charts for children with a diagnosis of HCH. Mixed longitudinal anthropometric data and genetic analysis results were collected from 14 European specialized skeletal dysplasia centers. Growth charts were generated using Generalized Additive Models for Location, Scale, and Shape. Measurements for height (983), weight (896), and HC (389) were collected from 188 (79 female) children with a diagnosis of HCH aged 0-18 years. Of the 84 children who underwent genetic testing, a pathogenic variant in FGFR3 was identified in 92% (77). The data were used to generate growth references for height, weight, and HC, plotted as charts with seven centiles from 2nd to 98th, for ages 0-4 and 0-16 years. HCH-specific growth charts are important in the clinical care of these children. They help to identify if other comorbidities are present that affect growth and development and serve as an important benchmark for any prospective interventional research studies and trials.

Autosomal recessive otospondylo-mega-epiphyseal dysplasia: comprehensive clinical review of a pediatric cohort.

Autosomal recessive otospondylo-mega-epiphyseal dysplasia (OSMEDB) is characterized by short stature with short limbs, dysmorphic facial features, and hearing loss, which is caused by biallelic, loss-of-function, variants in the COL11A2 gene. Geno-phenotypic data from the medical records of eight affected individuals from five unrelated families was abstracted, recorded in an Excel spreadsheet and analyzed using simple frequency analysis. Either short femora or short extremities with or without other ultrasonographic abnormalities were demonstrated in five patients antenatally. The mean height was -2.29 SDS. Pectus deformity, including either chest asymmetry or pectus excavatum, was present in five patients. Bilateral hearing loss was verified in all patients. Severe speech delay and learning disabilities were present in two patients whose deafness was realized after the age of 12 months. Four novel loss-of-function variants in COL11A2 were found in this cohort. We present novel geno-phenotypic findings in a pediatric cohort with OSMEDB. The age of manifestation of short stature was variable, ranging from birth to middle childhood, and the severity of short stature varied even within the same family. Hearing loss may not be evident in the neonatal period and manifest later in OSMEDB. Intermittent hearing tests should be performed for early intervention of neurolinguistic delay and learning disabilities.

Expanding the phenotype of anauxetic dysplasia caused by biallelic NEPRO mutations: A case report.

The cartilage hair hypoplasia and anauxetic dysplasia (CHH-AD) spectrum encompasses a group of rare skeletal disorders, with anauxetic dysplasia (ANXD) at the most severe end of the spectrum. Biallelic variants in RMRP, POP1, and NEPRO (C3orf17) have previously been associated with the three currently recognized ANXD types. Generally, all types are characterized by severe short stature, brachydactyly, skin laxity, joint hypermobility and dislocations, and extensive skeletal abnormalities visible on radiological evaluation. Thus far, only five patients with type 3 anauxetic dysplasia (ANXD3) have been reported. Here, we describe one additional ANXD3 patient. We provide a detailed physical and radiological evaluation of this patient, in whom we identified a homozygous variant, c.280C > T, p.(Arg94Cys), in NEPRO. Our patient presented with clinically relevant features not previously described in ANXD3: atlantoaxial subluxation, extensive dental anomalies, and a sagittal suture craniosynostosis resulting in scaphocephaly. We provide an overview of the literature on ANXD3 and discuss our patient's characteristics in the context of previously described patients. This study expands the phenotypic spectrum of ANXD, particularly ANXD3. Greater awareness of the possibility of atlantoaxial subluxation, dental anomalies, and craniosynostosis may lead to more timely diagnosis and treatment.

Association of Meier-Gorlin and microcephalic osteodysplastic primordial dwarfism type II clinical features in an individual with CDK5RAP2 primary microcephaly.

Autosomal recessive primary microcephaly type 3 (MCPH3) caused by pathogenic variations in CDK5RAP2, is characterized by sensorineural hearing loss, abnormality of skin pigmentation, ocular defects and severe microcephaly associated with neurodevelopmental delay. In this study, we expand the phenotype of MCPH3 as we describe a 10-year-old girl with a biallelic exonic frameshift variant in CDK5RAP2 displaying previously unreported features usually associated with Meier-Gorlin and microcephalic osteodysplastic primordial dwarfism type II (MOPDII). We further describe the clinical phenotype of this form of centrosomal-based primary microcephaly and emphasize the importance of skeletal defect screening in affected individuals.

Hipocondroplasia en pediatría: reporte de un caso / Hypocondroplasya in pediatrics: case study / Hipocondroplasia em pediatia: relato de caso

La hipocondroplasia es una displasia esquelética caracterizada por baja estatura, constitución robusta, brazos y piernas desproporcionadamente cortos, manos y pies anchos y cortos, leve laxitud articular y macrocefalia. Los niños generalmente se presentan como pequeños, con velocidad de crecimiento disminuida, que conduce a una baja estatura y desproporción de las extremidades. La hipocondroplasia en la mayoría de los casos se hereda con carácter autosómico dominante, aunque se detectan numerosos casos esporádicos. El diagnóstico requiere una exhaustiva anamnesis y adecuada exploración física. Es importante valorar algunos indicadores de crecimiento como: peso para la edad, longitud/talla para la edad, relación entre peso y longitud/talla, velocidad de crecimiento, talla diana genética, medidas de segmentos corporales, entre otros. Las radiografías esqueléticas permiten diagnosticar la mayoría de las displasias óseas. Los estudios moleculares suelen ser la prueba de confirmación y se solicitan ante una sospecha diagnóstica. Es importante incluir las displasias óseas en el diagnóstico diferencial de la talla baja y tenerlas en cuenta ante cualquier caso de talla baja disarmónica con alteraciones fenotípicas. La hipocondroplasia en la actualidad, no es una indicación aprobada para tratamiento con hormona del crecimiento. Se presenta un caso clínico de una niña de 14 meses, con talla baja severa, desproporcionada, que presentó dificultades para llegar al diagnóstico definitivo de hipocondroplasia.

Hypochondroplasia is a skeletal dysplasia characterized by short height, robust build, disproportionately short arms and legs, short and broad hands and feet, mild joint laxity, and macrocephaly. Children generally show slow growth rate, which leads to short stature and limb disproportion. Hypochondroplasia is mostly inherited with an autosomal dominant character, although many sporadic cases have been detected. Diagnosis requires a thorough history and adequate physical examination. It is important to assess some growth indicators such as: weight for age, length/height for age, relationship between weight and length/height, growth speed, genetic target height, measurements of body segments, among others. Skeletal XRs can diagnose most bone dysplasias. Molecular studies are usually the confirmatory test and are requested when a diagnosis is suspected. It is important to include bone dysplasias in the differential diagnosis of short stature and to take them into account for any disharmonious short stature with phenotypic alterations. Hypochondroplasia is currently not an approved indication for growth hormone therapy. We present a clinical case of a 14-month-old girl, with a severe, disproportionate short stature, who presented difficulties in her definitive hypochondroplasia diagnosis.

A hipocondroplasia é uma displasia esquelética caracterizada por baixa estatura, constituição robusta, braços e pernas desproporcionalmente curtos, mãos e pés largos e curtos, frouxidão articular leve e macrocefalia. As crianças geralmente são pequenas, com diminuição da velocidade de crescimento, o que leva à baixa estatura e desproporção dos membros. A hipocondroplasia na maioria dos casos é herdada com caráter autossômico dominante, embora sejam detectados numerosos casos esporádicos. O diagnóstico requer uma história completa e um exame físico adequado. É importante avaliar alguns indicadores de crescimento como: peso para idade, comprimento/altura para idade, relação entre peso e comprimento/altura, taxa de crescimento, estatura alvo genético, medidas de segmentos corporais, entre outros. As radiografias esqueléticas permitem o diagnóstico da maioria das displasias ósseas. Os estudos moleculares são geralmente o teste de confirmação e são solicitados quando há suspeita de diagnóstico. É importante incluir as displasias ósseas no diagnóstico diferencial da baixa estatura e considerá-las em qualquer caso de baixa estatura desarmônica com alterações fenotípicas. A hipocondroplasia não é atualmente uma indicação aprovada para o tratamento com hormônio de crescimento. Apresenta-se o caso clínico de uma menina de 14 meses, com baixa estatura grave e desproporcional, que apresentou dificuldades em chegar ao diagnóstico definitivo de hipocondroplasia.

A very rare syndrome and its rare urological complication: Incomplet bladder duplication in Robinow syndrome.

OBJECTIVES: Robinow syndrome is a very rare syndrome characterized by short stature, extremity deformities, costovertebral abnormalities, renal/external genital malformations, and fetal facial appearance. It might be inherited by either autosomal dominant or severe recessive form. Diagnosis is generally established by the aid of genetic mutation and phenotypic findings. The urogenital component of the disease frequently presents with microgenitalia such as micropenis and/or cryptorchidism. METHODS: Herein, a four-year-old boy with Robinow syndrome accompanied by incomplete bladder duplication is discussed. RESULTS: The duplication in the bladder was screened by cystoscopy and corrective surgery was performed. CONCLUSIONS: This rare manifestation is the first for urological findings of Robinow syndrome in literature.

Phenotypic continuum between POLE-related recessive disorders: A case report and literature review.

POLE is a pleiotropic gene with phenotypic expression of pathogenic variants depending on the type of variant, impact on the protein, and mode of inheritance. Heterozygous missense variants located within the exonuclease domain have been shown to result in polymerase proofreading-associated polyposis (PPAP) which is characterized by an increased risk for colon polyps and colorectal cancer. Biallelic variants resulting in markedly reduced amounts of normal protein have been reported in two separate recessive pediatric syndromes: facial dysmorphism, immunodeficiency, livedo, and short stature as well as intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenital, and genital anomalies. Here we report two siblings identified to have POLE c.1686 + 32C > G in trans with POLE p.(Glu709*) via exome sequencing. A detailed review of the reported phenotypes in these two siblings and from available literature revealed that individuals with biallelic POLE pathogenic variants resulting in partial loss-of-function present with a similar phenotype: short stature and facial dysmorphism with or without immunodeficiency. These data suggest a phenotypic continuum between the previously reported POLE-related recessive disorders.

LCN2 is a new diagnostic biomarker and potential therapeutic target in idiopathic short stature.

Idiopathic short stature (ISS) is the most common paediatric endocrine disease. However, the underlying pathology of ISS remains unclear. Currently, there are no effective diagnostic markers or therapeutic strategies available for ISS. In this study, we aimed to identify differential plasma protein expression and novel biomarkers in patients with ISS, and elucidate the biological functions of candidate proteins in ISS pathogenesis. Four specimen pairs from four ISS children and age-/sex-matched control individuals were subjected to proteomics analysis, and 340 samples of children with a mean age 9.73 ± 0.24 years were utilized to further verify the differentially expressed proteins by enzyme-linked immunosorbent assay (ELISA). The receiver-operating characteristic (ROC) curve and the area under the ROC curve (AUC) were plotted. A total of 2040 proteins were identified, of which 84 were differentially expressed. In vitro and in vivo experiments confirmed the biological functions of these candidate proteins. LCN2 overexpression in ISS was verified using ELISA. Meanwhile, LCN2 showed high sensitivity and specificity in discriminating children with ISS from those with growth hormone deficiency, precocious puberty and normal control individuals. The upregulated expression of LCN2 not only suppressed food intake but also impaired chondrocyte proliferation and bone growth in chondrocytes and rats. As a result, the rats presented a short-stature phenotype. Subsequently, we found that bone growth inhibition recovered after LCN2 overexpression was stopped in immature rats. To our knowledge, this is the first study to report that LCN2 may be a significant target for ISS diagnosis and treatment.

De novo heterozygous variants in KIF5B cause kyphomelic dysplasia.

Kyphomelic dysplasia is a heterogeneous group of skeletal dysplasias characterized by severe bowing of the limbs associated with other variable findings, such as narrow thorax and abnormal facies. We searched for the genetic etiology of this disorder. Four individuals diagnosed with kyphomelic dysplasia were enrolled. We performed whole-exome sequencing and evaluated the pathogenicity of the identified variants. All individuals had de novo heterozygous variants in KIF5B encoding kinesin-1 heavy chain: two with c.272A>G:p.(Lys91Arg), one with c.584C>A:p.(Thr195Lys), and the other with c.701G>T:p.(Gly234Val). All variants involved conserved amino acids in or close to the ATPase activity-related motifs in the catalytic motor domain of the KIF5B protein. All individuals had sharp angulation of the femora and humeri, distinctive facial features, and neonatal respiratory distress. Short stature was observed in three individuals. Three developed postnatal osteoporosis with subsequent fractures, two showed brachycephaly, and two were diagnosed with optic atrophy. Our findings suggest that heterozygous KIF5B deleterious variants cause a specific form of kyphomelic dysplasia. Furthermore, alterations in kinesins cause various symptoms known as kinesinopathies, and our findings also extend the phenotypic spectrum of kinesinopathies.

Phenotypic and mutational spectrum of ROR2-related Robinow syndrome.

Robinow syndrome is characterized by a triad of craniofacial dysmorphisms, disproportionate-limb short stature, and genital hypoplasia. A significant degree of phenotypic variability seems to correlate with different genes/loci. Disturbances of the noncanonical WNT-pathway have been identified as the main cause of the syndrome. Biallelic variants in ROR2 cause an autosomal recessive form of the syndrome with distinctive skeletal findings. Twenty-two patients with a clinical diagnosis of autosomal recessive Robinow syndrome were screened for variants in ROR2 using multiple molecular approaches. We identified 25 putatively pathogenic ROR2 variants, 16 novel, including single nucleotide variants and exonic deletions. Detailed phenotypic analyses revealed that all subjects presented with a prominent forehead, hypertelorism, short nose, abnormality of the nasal tip, brachydactyly, mesomelic limb shortening, short stature, and genital hypoplasia in male patients. A total of 19 clinical features were present in more than 75% of the subjects, thus pointing to an overall uniformity of the phenotype. Disease-causing variants in ROR2, contribute to a clinically recognizable autosomal recessive trait phenotype with multiple skeletal defects. A comprehensive quantitative clinical evaluation of this cohort delineated the phenotypic spectrum of ROR2-related Robinow syndrome. The identification of exonic deletion variant alleles further supports the contention of a loss-of-function mechanism in the etiology of the syndrome.

Novel compound heterozygous variants in XYLT1 gene caused Desbuquois dysplasia type 2 in an aborted fetus: a case report.

BACKGROUND: Desbuquois dysplasia type 2 (DBQD2) is an infrequent dysplasia with a wide range of symptoms, including facial deformities, growth retardation and short long bones. It is an autosomal recessive disorder caused by mutations in the XYLT1 gene that encodes xylosyltransferase-1. CASE PRESENTATION: We studied an aborted fetus from Iranian non-consanguineous parents who was therapeutically aborted at 19 weeks of gestation. Ultrasound examinations at 18 weeks of gestation revealed growth retardation in her long bones and some facial problems. Whole-exome sequencing was performed on the aborted fetus which revealed compound heterozygous XYLT1 mutations: c.742G>A; p.(Glu248Lys) and c.1537 C>A; p.(Leu513Met). Sanger sequencing and segregation analysis confirmed the compound heterozygosity of these variants in XYLT1. CONCLUSION: The c.1537 C>A; p.(Leu513Met) variant has not been reported in any databases so far and therefore is novel. This is the third compound heterozygote report in XYLT1 and further supports the high heterogeneity of this disease.

Orthopedic concerns of a child with short stature.

PURPOSE OF REVIEW: Pediatric short stature poses severe concerns to the patient, parents, and physicians. Management for pediatric short stature is still widely debated due to heterogenous etiological factors and treatment options. This review will address the approach to pediatric short stature, commonly within the subset of skeletal dysplasia resulting in disproportionate short stature. The following will be discussed: the etiology, clinical, and radiological evaluations, and management for pediatric short stature. RECENT FINDINGS: Early recognition of short stature and appropriate referrals is shown to benefit the patient and reduce parental concern. A multidisciplinary team, comprising an orthopedic surgeon, is fundamental to provide holistic care and ensure overall good quality of life. Advancements in clinical diagnostic tools and diversified treatment modalities today provides optimism in managing pediatric short stature. SUMMARY: Skeletal dysplasia can be treated with good prognosis if diagnosed and managed early. Thorough clinical, radiological, laboratory, and even genetic investigations are important to differentiate and manage various types of skeletal dysplasia. Our review will provide a comprehensive and up-to-date approach to skeletal dysplasia for pediatric orthopedic surgeons, and indications for physicians to refer patients with suspected short stature to pediatric orthopedic surgeons.

Copy number variations residing outside the SHOX enhancer region are involved in Short Stature and Léri-Weill dyschondrosteosis.

BACKGROUND: SHOX enhancer CNVs, affecting one or more of the seven recognized evolutionary conserved non-coding elements (CNEs) represent one of the most frequent cause of SHOX-haploinsufficiency. During the diagnostic workflow deletions/duplications have been identified downstream SHOX not including any of the these CNEs. METHODS: Fine tiling aCGH and breakpoint PCR were used to characterize the critical interval and to search for novel alterations in a cohort of selected patients. RESULTS: Screening of 252 controls provided evidence that duplications in this area represent likely benign variants whereas none of the deletions were detected. These findings suggested that other alterations relevant for SHOX-haploinsufficiency might be missed by the standard diagnostic methods. To identify such undisclosed elements, the aCGH was used to reanalyze 52 unresolved cases with clinical features strongly suggestive of SHOX-haploinsufficiency. This analysis followed by the screening of 210 patients detected two partially overlapping small deletions of ~12 and ~8 kb in four unrelated individuals, approximately 15 kb downstream SHOX, that were absent in 720 normal stature individuals. CONCLUSION: Our results strengthen the hypothesis that alterations of yet unidentified cis-regulatory elements residing outside those investigated through conventional methods, might explain the phenotype in ISS/LWD patients thus enlarging the spectrum of variants contributing to SHOX-haploinsufficiency.

Clinical Profiles and Genetic Spectra of 814 Chinese Children With Short Stature.

CONTEXT: Data and studies based on exome sequencing for the genetic evaluation of short stature are limited, and more large-scale studies are warranted. Some factors increase the likelihood of a monogenic cause of short stature, including skeletal dysplasia, severe short stature, and small for gestational age (SGA) without catch-up growth. However, whether these factors can serve as predictors of molecular diagnosis remains unknown. OBJECTIVE: We aimed to explore the diagnostic efficiency of the associated risk factors and their exome sequences for screening. METHODS: We defined and applied factors that increased the likelihood of monogenic causes of short stature in diagnostic genetic tests based on next-generation sequencing (NGS) in 814 patients with short stature and at least 1 other factor. RESULTS: Pathogenic/likely pathogenic (P/LP) variants in genes, copy number variations, and chromosomal abnormalities were identified in 361 patients. We found P/LP variants among 111 genes, and RASopathies comprised the most important etiology. Short stature combined with other phenotypes significantly increased the likelihood of a monogenic cause, including skeletal dysplasia, facial dysmorphism, and intellectual disability, compared with simple severe short stature (<-3 SD scores). We report novel candidate pathogenic genes, KMT2C for unequivocal growth hormone insensitivity and GATA6 for SGA. CONCLUSION: Our study identified the diagnostic characteristics of NGS in short stature with different risk factors. Our study provides novel insights into the current understanding of the etiology of short stature in patients with different phenotypes.

Management of growth failure and other endocrine aspects in patients with Noonan syndrome across Europe: A sub-analysis of a European clinical practice survey.

AIM: To date, there is a lack of international guidelines regarding the management of the endocrine features of individuals with Noonan syndrome (NS). The aim was to develop a clinical practice survey to gather information on current treatment and management of these patients across Europe. MATERIALS AND METHODS: A group of 10 experts from three clinical specialities involved in the management of NS patients (clinical geneticists, paediatric endocrinologists, and paediatric cardiologists) developed a 60-question clinical practice survey. The questionnaire was implemented in Survey Monkey and sent to physicians from these three specialities via European/national societies. Contingency tables and the Chi-Squared test for independence were used to examine differences between specialities and countries. RESULTS: In total, responses of 364 specialists (paediatric endocrinologists, 40%; geneticists, 30%; paediatric cardiologists, 30%) from 20 European countries were analysed. While endocrinologists mostly referred to national growth charts for the general population, geneticists mostly referred to NS-specific growth charts. Approximately half of the endocrinologists perform growth hormone (GH) stimulation tests in short patients with low IGF1 levels. Two thirds of endocrinologists begin GH treatment for short patients in early childhood (4-6.9 years), and over half of them selected a threshold of -2 standard deviation score (SDS) according to national growth charts. The main concerns about GH treatment appear to be presence of hypertrophic cardiomyopathy (HCM) (59%), increased risk of malignancy (46%), and limited efficacy (31%). When asked if they consider HCM as a contraindication for GH treatment, one third of respondents skipped this question, and among those who replied, two thirds selected 'cannot answer', suggesting a high level of uncertainty. A total of 21 adverse cardiac responses to GH treatment were reported. Although most respondents had not encountered any malignancy during GH treatment, six malignancies were reported. Finally, about half of the endocrinologists expected a typical final height gain of 1-1.5 SDS with GH treatment. CONCLUSION: This survey describes for the first time the current clinical practice of endocrine aspects of NS across Europe and helps us to identify gaps in the management but also in the knowledge of this genetic disorder.

3-M syndrome - a primordial short stature disorder with novel CUL7 mutation in two Indian patients.

OBJECTIVE: To evaluate the cause of short stature in children. CASE PRESENTATION: Two children with suspected skeletal dysplasia and short stature were evaluated. CONCLUSIONS: The 3-M syndrome is a primordial growth disorder manifesting severe postnatal growth restriction, skeletal anomalies and prominent fleshy heels. The 3-M syndrome is a genetically heterogeneous disorder and the phenotype is similar. This is a rare autosomal recessive disorder with normal intellect. Two affected children have been identified by whole-exome sequencing. One patient harboured a compound heterozygous variant and the other was a homozygous missense variant. The genetic diagnosis helped in counselling the families and facilitated prenatal diagnosis in one (case 1) family.

Prevalence and determinants of stunting among preschool and school-going children in the flood-affected areas of Pakistan / Prevalência e determinantes da baixa estatura entre crianças em idade pré escolar e em idade escolar nas áreas afetadas pelas enchentes do Paquistão

Stunting is a significant public health problem in low- and middle-income countries. This study assessed the prevalence of stunting and associated risk factors of stunting among preschool and school-going children in flood-affected areas of Pakistan. A cross-sectional study was conducted by visiting 656 households through multi-stage sampling. Respondent's anthropometric measurements, socio-demographic information and sanitation facilities were explored. A logistic regression model was used to determine determinants of stunting, controlling for all possible confounders. The overall prevalence of stunting in children was 40.5%, among children 36.1% boys and 46.3% of girls were stunted. The prevalence of stunting in under-five children was 50.7%. Female children (OR=1.35, 95% CI:0.94-2.0), children aged 13-24 months (OR=6.5, 95% CI: 3.0-13.9), mothers aged 15-24 years (OR=4.4, 95% CI: 2.6-7.2), joint family (OR=2.1, 95% CI: 1.4-3.0) did not have access to improved drinking water (OR=3.3, 95% CI: 1.9-5.9), and the toilet facility (OR=2.8, 95% CI, 1.9-4.3), while the children from district Nowshera (OR=1.7, 95% CI: 0.9-3.2) were significantly (P<0.05) associated in univariate analysis. The regression model revealed that child age, maternal age, family type, quality of water, and toilet facility, were the significant (P<0.05) factors contributing to child stunting in the flood-hit areas. Identification of key factors might be helpful for policymakers in designing comprehensive community-based programs for the reduction of stunting in flood-affected areas. In disasters such as flood, the detrimental consequences of the stunting problem could be even more on children. Evidence-based education and care must be provided to the families in the flood-affected regions to reduce the stunting problem. The determinants of stunting should [...].

A baixa estatura é um problema significativo de saúde pública em países de baixa e média renda. Este estudo avaliou a prevalência de nanismo e os fatores de risco associados de nanismo entre crianças em idade pré-escolar e em idade escolar em áreas afetadas por inundações do Paquistão. Foi realizado um estudo transversal visitando 656 domicílios por meio de amostragem em múltiplos estágios. As medidas antropométricas do entrevistado, informações sociodemográficas e instalações de saneamento foram exploradas. Um modelo de regressão logística foi usado para determinar os determinantes do nanismo, controlando todos os possíveis fatores de confusão. A prevalência geral de baixa estatura em crianças foi de 40,5%, entre as crianças 36,1% dos meninos e 46,3% das meninas com baixa estatura. A prevalência de baixa estatura em crianças menores de 5 anos foi de 50,7%. Crianças do sexo feminino (OR = 1,35, IC de 95%: 0,94-2,0), crianças de 13-24 meses (OR = 6,5, IC de 95%: 3,0-13,9), mães de 15-24 anos (OR = 4,4, IC de 95%: 2,6-7,2), família conjunta (OR = 2,1, IC 95%: 1,4-3,0) não tiveram acesso a água potável de qualidade (OR = 3,3, IC 95%: 1,9-5,9) e a banheiro (OR = 2,8, IC de 95%, 1,9-4,3), enquanto as crianças do distrito de Nowshera (OR = 1,7, IC de 95%: 0,9-3,2) foram significativamente (P < 0,05) associadas na análise univariada. O modelo de regressão revelou que a idade da criança, idade materna, tipo de família, qualidade da água e banheiro foram os fatores significativos (P < 0,05) que contribuíram para a baixa estatura infantil nas áreas afetadas pelas enchentes. A identificação de fatores-chave pode ser útil para os formuladores de políticas no planejamento de programas comunitários abrangentes para a redução da baixa estatura em áreas afetadas pelas enchentes. Em desastres como enchentes, as consequências prejudiciais do problema de baixa estatura podem [...].

A 10-Year-Old Boy with Short Stature and Microcephaly, Diagnosed with Moyamoya Syndrome and Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II).

BACKGROUND Moyamoya syndrome is a rare cerebrovascular condition caused by blockage of the arteries of the basal ganglia. The Japanese word "moyamoya" means "a puff of smoke" which describes the appearance of the collateral compensatory vessels that develop over time. Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by microcephaly and short stature. In up to 25% of patients with MOPD II, there is an association with moyamoya syndrome. This report is of a Syrian boy diagnosed with moyamoya syndrome and MOPD II. CASE REPORT A 10-year-old boy was referred to our pediatric endocrinology unit for short stature (-11.1 standard deviations). Exploration of the oral cavity showed dental malposition. Laboratory tests revealed mild thrombocytosis and hypernatremia. Glucagon-based growth hormone-stimulation testing revealed pathology, with growth hormone levels peaked at 30 minutes below 1 ng/ml. No abnormalities of carbohydrate metabolism or heart function were identified. Neuropsychological assessment found moderate to severe intellectual disability. Imaging studies showed osteoporosis, bilateral coxa vara, diffuse platyspondyly without scoliosis, malrotation of the left kidney, severe microcephaly with simplified convolution pattern, and moyamoya features with secondary brain atrophy. A genetic study identified a mutation in both alleles of the pericentrin (PCNT) gene, enabling the diagnosis of microcephalic osteodysplastic primordial dwarfism type II. CONCLUSIONS This case highlights the importance of identifying the cause of short stature in children and genetic syndromes that may be linked with other abnormalities. MOPDII associated with moyamoya syndrome was diagnosed by cerebrovascular imaging, which led to a multidisciplinary approach to management.