Child Of Consanguineous Parents Research Articles

The third patient of ACACA-related acetyl-CoA carboxylase deficiency with seizure and literature review

Pathogenic variants in ACACA are the cause of acetyl-CoA carboxylase deficiency with an autosomal recessive inheritance that is identified by hypotonia, motor, and intellectual developmental delay. In this article, we describe a seven-year-old boy who is the child of consanguineous parents with a homozygous variant in ACACA (NM_198834.3:c.6641C > A, p.P2214H) that was detected by Whole-Exome Sequencing and confirmed by Sanger sequencing. This is the first reported patient of acetyl-CoA carboxylase deficiency that results from a homozygous pathogenic variant in the ACACA gene in the Iranian family. The proband presents with motor and intellectual developmental delay, muscle weakness, language disorder, facial dysmorphism, and poor growth. The patient discussed here is similar to other patients that were previously published; however, we were able to identify seizure that has hitherto not been reported. This paper describes the third person with a novel variant in the ACACA gene in the world that accounts for acetyl-CoA carboxylase deficiency and implicates the clinical spectrum of the disease. Finally, we describe an individual-based review of the symptoms associated with acetyl-CoA carboxylase deficiency. So far, only two acetyl-CoA carboxylase deficiency patients have been reviewed in the literature.

Konjenital Ağrı Duyarsızlığı ile Anhidrosis Sendromu: Diyala vilayeti / Irak’tan Bir Olgu Sunumu

Congenital insensitivity to pain with anhidrosis syndrome (CIPA); is a rare autosomal recessive disorder presenting with pain insensitivity, sweating inability, and intellectual disability. The incapability to sense pain and temperature often leads to recurrent severe and inadvertent self-inflicted harm; these can result in severe complications, as patients settle slowly from skin and bone harm. We present a case of a four-year-old boy with a diagnosis of CIPA, after repeated visits to the hospital emergency department for repeated chest and both ankle joint infections, which prompted further investigations. Case report A four-year-old boy was admitted to Albatool teaching hospital for maternity and children in Baqubah, Diyala, Iraq because of recurrent chest and both ankle joints infection. He is the second child of consanguineous parents. His six-year-old sister is normal. The mother noticed early after birth that her child was suffering from high fever, he was not responding to pricking and injections, and he never sweats with intolerance to warm weather. Examination revealed mental developmental delay, absent upper and lower canine teeth, napkin and face dermatitis which was intractable to therapy, and deep pus discharging ulcers of both heels. Radiology of feet shows signs of osteomyelitis. There is a history of the same disease in two male cousins who died at age of three and five years respectively, the overall clinical context warranted a clinical suspicion of CIPA. Early diagnosis of this extremely rare disease is very important for the treatment and prevention of complications. Conclusion: This case report shows that a clinician should suspect to investigate for CIPA when managing kids with multiple inadvertent self-inflicted harms, anhidrosis, and pain insensitivity.

Do Parental Comorbidities Affect the Severity of Autism Spectrum Disorder?

Background Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders characterized by defective social communication and interaction with a repetitive pattern of monotonous or stereotyped behavior.Although the exact etiology of ASD is unknown, many factors may be implicated in the development of ASD.We aimed to determine the correlation between specific parental factors and Autism Treatment Evaluation Checklist (ATEC) scores. Methods This cross-sectional study was conducted at the Prince Nasser Bin Abdulaziz Center for Autism, Autism Center for Excellence, and Academy of Special Education for Autism in Riyadh, Saudi Arabia. We enrolled children diagnosed with ASD and their parents from these centers. Data were collected through self-administered questionnaires to the patients' parents. Results All included children were <18 years old. In total, 71 (92.2%) children were male and six (7.8%) were female. Further, 77 (100%) patients were diagnosed with autistic disorder. Children of consanguineous parents, underweight mothers and obese fathers, mothers with a history of depression during pregnancy, and mothers aged ≥31 years during pregnancy tend to have a higher mean ATEC score. The health domain was the most significantly correlated with ATEC scores, with a Pearson correlation of 0.880. In linear regression analysis, only maternal depression during pregnancy was significantly correlated with ATEC scores. Conclusion Our patients had a mean ATEC score of 86.2. The health domain was the most significantly correlated with ATEC scores, with a Pearson correlation of 0.880. Linear regression analysis revealed that consanguinity, parental chronic disease, parental allergy, smoking, druguse during pregnancy, paternal and maternal body mass index (BMI), and siblingnumber were not significantly correlated with ATEC scores (P=0.701, 0.693, 0.133, 0.874, 0.982, 0.255, 0.778, and 0.502, respectively). However, maternal depression during pregnancy was significantly correlated with ATEC scores (P=0.055).

The Urofacial (Ochoa) Syndrome

We reported the case of a child aged six-years-old, the second child of consanguineous parents, the father reported that she has suffered from episodes of urinary tract infection, and enuresis. She was admitted in our department for an urinary tract infection. The clinical examination showed a characteristic, inverted, facial expression.

Second Report of Chronic Granulomatous Disease in Jordan: Clinical and Genetic Description of 31 Patients From 21 Different Families, Including Families From Lybia and Iraq.

Chronic granulomatous Disease (CGD) is a rare innate immunodeficiency disorder caused by mutations in one of the six genes (CYBA, CYBB, NCF1, NCF2, NCF4, and CYBC1/EROS) encoding the superoxide-producing nicotinamide adenine dinucleotide phosphate (NADPH)—oxidase complex in phagocytes. In the Western population, the most prevalent form of CGD (about two-thirds of all cases) is the X-linked form (X-CGD) caused by mutations in CYBB. The autosomal recessive forms (AR-CGD), due to mutations in the other genes, collectively account for the remaining one-third of CGD cases. We investigated the clinical and molecular features of 22 Jordanian, 7 Libyan, and 2 Iraqi CGD patients from 21 different families. In addition, 11 sibling patients from these families were suspected to have been died from CGD as suggested by their familial and clinical history. All patients except 9 were children of consanguineous parents. Most of the patients suffered from AR-CGD, with mutations in CYBA, NCF1, and NCF2, encoding p22phox, p47phox, and p67phox proteins, respectively. AR-CGD was the most frequent form, in Jordan probably because consanguineous marriages are common in this country. Only one patient from non-consanguineous parents suffered from an X910 CGD subtype (0 indicates no protein expression). AR670 CGD and AR220 CGD appeared to be the most frequently found sub-types but also the most severe clinical forms compared to AR470 CGD. As a geographical clustering of 11 patients from eight Jordanian families exhibited the c.1171_1175delAAGCT mutation in NCF2, segregation analysis with nine polymorphic markers overlapping NCF2 indicates that a common ancestor has arisen ~1,075 years ago.

Sindrome de allgrove en niños. Reporte de 11 casos

Background. Allgrove Syndrome is a very rare genetic disease, which is inherited in an autosomal recessive way. The responsible gene is the AAAS, that encodes the protein ALADIN. It occurs most often in children of consanguineous parents. It is characterized by the classic triad of achalasia, alacrima, and adrenal insufficiency due to resistance to ACTH; the presence of two of the three previous manifestation events are required to establish the diagnosis. There is also a high frequency of the neurologic symptoms. Objective. Describe the clinical characteristics, age of presentation and evolution in 11 patients with Allgrove Syndrome. Methods. 11 clinical cases compatible with Allgrove Syndrome of presentation in childhood are retrospectively reviewed. Results. The average age at diagnosis was 5.9 years (range 1-16 years old). There was a predominance of the female sex (n = 7). The most common symptoms were postprandial vomiting and alacrima, present in 100% of the cases at the time of diagnosis. Adrenal insufficiency was not common; it was only documented in one patient. There was consanguinity between parents in 62.5% of the cases. Conclusions. Allgrove Syndrome is an uncommon cause of dysphagia, chronic vomiting and failure to grow in children. In case of any documented case of achalasia it is suggested to question in a directed way the presence of alacrima and adrenal insufficiency data such as seizures, hyperpigmentation of the skin and neurological alterations.

SUN-033 A Rare Case: Bone Pain and Continued Linear Growth in a Young Adult Male Due to Aromatase Deficiency

Introduction:Aromatase, the product of CYP19A1, catalyzes the conversion of androgens to estrogens. 46, XX infants with aromatase deficiency, due to androgen excess, present with ambiguous genitalia at birth. In 46, XY individuals, however, the subtle phenotypic features make the diagnosis even more difficult. Less than 15 male cases were reported in the literature and we present the first case of aromatase deficiency diagnosed in Taiwan.Clinical Case:A 23-year-old man, Burman overseas student of Chinese descent, presented to an orthopedist with a two-year history of left ankle pain, which was diagnosed as gout by his previous physician. Unexpectedly, unfused growth plates were discovered so he was referred to our pediatric endocrine clinic for evaluation. Reviewing his past history, we learned he is the third child of consanguineous parents. His mother experienced deepening of voice during this pregnancy which resolved following parturition. He was 177 cm tall at the age of 19. At the time he presented to our clinic, he weighed 95.3 kg and was 183 cm tall. Physical exam showed the ratio of U/L segment to be 0.82, stretched penile length 6.5 cm, bilateral testes > 25 mL, pubic hair at Tanner stage V, and presence of genu valgum. The skeletal age was 14 years and 6 months. Labs showed FSH 19.7 IU/L (0.7–11.1), LH 8.18 IU/L (0.8–7.6), total testosterone 1335 ng/dL (240–871), estradiol <20 pg/mL, DHEA-S 13.41 μmol/L (6.5–14.6), androstenedione 5.73 nmol/L (3.5–9.8) and 17-OH progesterone 6.55 nmol/L (2–10). GnRH (100 μg i.v) stimulation test showed a supranormal basal FSH level and a normal to higher LH response (FSH at baseline/peak were 23.0/38.6 IU/L; LH at baseline/peak were 8.81/47.7 IU/L). Under the clinical suspicion of aromatase deficiency, we performed genetic sequencing of CYP19A1 (NM_031226) and found a homozygous missense variant c.1108G>A (V370M), a previously reported pathogenic mutation.A diagnosis of aromatase deficiency was made. He also had hypertension (156/87 mmHg), dyslipidemia (T-cholesterol 236 mg/dL, LDL-C 175 mg/dL) and insulin resistance (AC glucose 87 mg/dL, insulin 23.5 μU/mL, HOMA-IR 5.0, Hb1Ac 5.6%). Bone mineral density of lumbar spine (DXA) showed a T-score of -2.8, consistent with the diagnosis of osteoporosis.Conclusion:Estrogen is pivotal for epiphyseal closure in both sexes. As demonstrated in this case, estrogen deficiency in men results in tall stature and eunuchoid habitus, while it is also associated with low bone density and metabolic syndrome. The gonadotropin response in this report suggests the inhibitory role of estrogen in the male HPG axis. Clinicians may consider this rare diagnosis for men in their late teens or early twenties, who have spontaneous initiation of puberty, presenting with bone pain and continued linear growth.

Hemolytic Uremic Syndrome: A Contemporary Pediatric Experience

Background: Hemolytic uremic syndrome (HUS) is a significant cause for complicated acute kidney injury. In Western countries, >90% of HUS are Shiga toxin Escherichia coli (STEC) associated. Methods: This is a retrospective review of all Israeli children diagnosed with HUS in 4 major medical centers in Israel during 1999–2016. Patients were categorized into 4 HUS etiological groups according to international guidelines: I, inherited or acquired damage to the complement cascade (“atypical HUS” [aHUS]); II, infection associated (“typical” HUS – STEC associated, Pneumococcus); III, coexisting disease; IV: other and unknown causes. Results: Seventy-five children with HUS were identified; the mean annual incidence was 1.5 ± 0.7 cases/10⁶ per year. Distribution according to etiological groups was: I: 24.0%; II: 14.7%; III: 9.3%; IV: 52.0%. Group I comprised high proportions of Arabs (55.6%), children of consanguineous parents (61.0%), and hypertension. Group II included a high proportion of children with diarrhea on presentation and central nervous system involvement. Only 5 (6.6%) had proven STEC-HUS. Group IV was similar in most characteristics to group II. Logistic regression analysis revealed 3 independent factors associated with the diagnosis of aHUS: consanguinity, lack of diarrhea, and lack of leukocytosis at presentation. Receiver operating analysis curve showed an area under the curve of 0.9 (95% CI 0.82–0.98). Conclusions: HUS incidence is lower in Israel than in most countries, especially because STEC-HUS is very rare. aHUS is the largest defined etiological group; some distinctive characteristics were identified that could facilitate its diagnosis. The current classification system leaves a high rate of “unknown cause” HUS.

CONGENITAL MYOPATHIES: NEMALINE AND TITINOPATHIES: P.235Recessive congenital fiber type disproportion caused by TPM3 mutation

Mutations in TPM3 gene represent a common cause of congenital fiber type disproportion (CFTD), but can also lead to other phenotypes like nemaline myopathy, cap myopathy, and congenital muscle stiffness. The clinical severity is also highly variable and genotype/phenotype correlations have been inconsistent. The majority of previously reported TPM3-associated diseases are dominantly acting, either inherited or de novo. Recessive cases are very rare and previously related to severe forms of recessive nemaline myopathy and one severely affected patient with CFTD. Here we present an autosomal recessive CFTD case harboring a novel homozygous mutation in TPM3 presenting with a mild proximal phenotype. Case Report: a 14-year-old female, only child of consanguineous parents. She was born hypotonic followed by delayed acquisition of motor milestones. Head support was achieved at the age of 6 months and gait at 30 months. At the time of the evaluation, she could walk for more than 1000 meters, climb stairs without support, but could never jump. The physical exam showed facial weakness, mild ptosis but no ophtalmoparesis and mild thoracic deformity. She presented a mild proximal cervical weakness combined with a moderate involvement of cervical flexors and no distal weakness. Muscle biopsy of the biceps brachii performed at the age of 4 years showed fiber type disproportion with type 1 predominance and smallness without other structural features like rods, nuclear centralization or cores. Whole exome sequencing revealed a novel homozygous missense variant (p.R179G) in exon 5 of TPM3 gene. The variant is not present in the population databases (EXAC, GNoMED, EVS), it is located in a very conserved residue and is predicted to be damaging according MetaSVM and MetaLR. Herein we presented a novel homozygous variant in TPM3 gene causing a mild CFTD expanding the phenotype-genotype correlations related to this gene and also adding a new variant associated with muscle disease.

Consanguineous Marriage and the Psychopathology of Progeny

Approximately 1 in 10 children worldwide are born to consanguineous parents. The literature on consanguinity and mental health of progeny is scarce despite the fact that many of the factors associated with consanguineous unions are also associated with mental health. To investigate if children of consanguineous parents are at increased risk of common mood disorders or psychoses. This investigation was a retrospective population-wide cohort study of all individuals born in Northern Ireland between January 1, 1971, and December 31, 1986, derived from the Child Health System data set and linked to nationwide administrative data sources on prescription medication and death records. Data from the Child Health System data set identified all 447 452 births delivered to mothers residing in Northern Ireland between 1971 and 1986. The final data set comprised 363 960 individuals, alive and residing in Northern Ireland in 2014, with full data on all variables. The dates of analysis were June 1 to October 31, 2017. Degree of parental consanguinity was assessed from questions asked of the parents during routine health visitor house calls within 2 weeks of the child's birth. Potential mental ill health was estimated by receipt of psychotropic medication in 2010 to 2014. Ever or never use was used for the main analysis, with sensitivity analyses using a cutoff of at least 3 months' prescriptions. Receipt of antidepressant or anxiolytic medications was used as a proxy for common mood disorders, whereas receipt of antipsychotic medications was used as a proxy indicator of psychoses. Of the 363 960 individuals (52.5% [191 102] male), 609 (0.2%) were born to consanguineous parents. After full adjustment for factors known to be associated with poor mental health, multilevel logistic regression models found that children of first-cousin consanguineous parents were more than 3 times as likely to be in receipt of antidepressant or anxiolytic medications (odds ratio, 3.01; 95% CI, 1.24-7.31) and more than twice as likely to be in receipt of antipsychotic medication (odds ratio, 2.13; 95% CI, 1.29-3.51) compared with children of nonrelated parents. A child of consanguineous parents is at increased risk of common mood disorders and psychoses.

Frequency of Inborn Errors of Metabolism in a Northeastern Iranian Sample with High Consanguinity Rates

Objective: Inborn errors of metabolism (IEMs) are disorders with various manifestations that occur mainly in the pediatric population. In countries where consanguineous marriage is common, the association between consanguinity and IEMs is highly important. No studies have been conducted in Iran examining the impact of consanguinity on IEMs. Methods: In this retrospective study, the incidences of metabolic disorders were evaluated for the years 2006 through 2016 in the North East Iran Regional Diagnostic Laboratory (Pardis Clinical and Genetic Laboratory). A total of 13,327 infants with clinical symptoms were referred and investigated for IEMs. Newborn screening was performed on samples from all patients suspected of having IEMs. Results: Of 13,327 infants examined, 60 different IEMs were diagnosed in 1,118. The most frequent disorders among our patients were glucose-6-phosphate dehydrogenase deficiency (G6PDD) (14.04%), methylmalonic and propionic acidurias (MMA/PA) (9.12%), phenylketonuria (PKU) (8%), and isovaleric acidemia (IVA) (6.98%). A significant difference was found in the prevalence of amino acid disorders between the offspring of consanguineous and those of non-consanguineous parents. No statistically significant differences were found between the 2 groups for organic or fatty acids, carnitine or urine cycles, or lysosomal storage disorders. A total of 707 of the 1,118 infants with metabolic diseases (63.24%) were children of consanguineous parents. These findings show that consanguinity can be an important factor in the inheritance of recessive mutations in a homozygous state. Conclusion: This study found a greater frequency of metabolic diseases in offspring of consanguineous parents than in those of non-consanguineous parents in a population with a high rate of consanguinity.

Colestase intra-hepática familiar progressiva: relato de dois casos

A colestase intra-hepática familiar progressiva (PFIC) é um grupo heterogêneo de doenças raras, de herança autossômica recessiva, que se apresenta com colestase hepatocelular devido a um defeito na secreção biliar, geralmente manifestada na infância. Suas características clínicas comuns são: icterícia na primeira infância, hepatosesplenomegalia, prurido intratável grave e retardo de crescimento. Não se conhece bem a epidemiologia dessas doenças, mas estima-se que a incidência seja de 1:50 mil a 1:100 mil nascimentos. A PFIC acomete igualmente ambos os sexos e tem sido relatada em diversas regiões geográficas. Descrevemos dois casos de irmãos, filhos de pais consanguíneos com a PFIC tipo 1. O presente relato busca ampliar o conhecimento médico dessas manifestações genéticas raras e auxiliar no diagnóstico precoce dos pacientes com a enfermidade.

A Genotype-First Approach for Clinical and Genetic Evaluation of Wolcott-Rallison Syndrome in a Large Cohort of Iranian Children With Neonatal Diabetes.

Wolcott-Rallison syndrome (WRS) is an extremely rare autosomal recessive condition, characterized by permanent neonatal diabetes mellitus (PNDM) associated with skeletal dysplasia, growth retardation and liver dysfunction. WRS is caused by biallelic mutations in the gene encoding eukaryotic translation initiation factor 2alpha kinase 3 (EIF2AK3). As part of a comprehensive study on clinical and genetic investigation of neonatal diabetes in an Iranian population, 60 unrelated Iranian subjects referred with PNDM were analyzed. All the probands were screened for KCNJ11, INS, ABCC8 and EIF2AK3 using a polymerase chain reaction-based sequencing approach. We identified 9 different variants in EIF2AK3 in 11 unrelated Iranian probands, of which 5 variants were shown to be novel and not reported previously. The diagnosis of WRS was made by molecular genetic testing and confirmed by clinical re-evaluation of the subjects. Clinical follow up of the affected individuals shows that in at least some of them, PNDM was associated with short stature, failure to thrive, neurodevelopmental delay, epilepsy and hepatic and renal dysfunction. There was a strong family history of neonatal diabetes in the families of the probands with a high mortality rate. WRS is a common cause of PNDM in children of consanguineous parents. Furthermore, clinical diagnosis of WRS would have been delayed or possibly missed without genetic testing because this study shows that the associated features of WRS might be obscured by a diagnosis of PNDM. Therefore EIF2AK3 should be considered for any infant and young child with PNDM, particularly if the parents are related.

Hematopoietic stem cell transplantation corrects osteopetrosis in a child carrying a novel homozygous mutation in the FERMT3 gene

Osteopetrosis (OPT) is a rare skeletal disorder with phenotypic and genotypic heterogeneity: a variety of clinical features besides the bony defect may be present, and at least ten different genes are known to be involved in the disease pathogenesis. In the framework of this heterogeneity, we report the clinical description of a neonate, first child of consanguineous parents, who had osteoclast-rich osteopetrosis and bone marrow failure in early life, but no other usual classical features of infantile malignant OPT, such as visual or hearing impairments. Because of the severe presentation at birth, the patient received Hematopoietic Stem Cell Transplantation (HSCT) at 2months of age with successful outcome. Post-HSCT genetic investigation by means of exome sequencing identified a novel homozygous mutation in the Fermitin Family Member 3 (FERMT3) gene, which was predicted to disrupt the functionality of its protein product kindlin 3. Our report provides information relevant to physicians for recognizing patients with one of the rarest forms of infantile malignant OPT, and clearly demonstrates that HSCT cures kindlin 3 deficiency with severe phenotype.

Sanjad-Sakati syndrome: Beyond the Middle-East

Sanjad-Sakati syndrome (OMIM 241410), also known as hypoparathyroidism-retardation-dysmorphism (HRD) syndrome, is a rare autosomal recessive syndrome of congenital hypoparathyroidism, mental retardation, and facial dysmorphism, reported almost exclusively in the Middle-Eastern children of consanguineous parents. Here, we present a 20-year-old male child from India presenting with childhood-onset, recurrent generalized seizures, which were poorly controlled with multiple antiepileptics. Along with intrauterine growth retardation, the patient had short stature and typical facial dysmorphism. Investigations revealed extensive intracranial calcifications, with hypoparathyroidism and severe hypocalcemia. This is only the third reported patient of HRD phenotype in a non-Arab patient and the first to present with multifocal dystonia. Thus, it is important to keep in mind untreated hypocalcemia in a patient of refractory seizures, with HRD possibly being no longer an exclusively Middle-Eastern disease.

Giant Herpes Labialis in a Child with DOCK8-deficient Hyper-IgE Syndrome

A 7-year-old girl, who was the first child of consanguineous parents and was diagnosed with DOCK8-deficient (homozygote large deletion, starts in exon 31 and extends at least to exon 48 of DOCK8 gene; kindly provided by Prof Dr. B. Grimbacher, Universitatsklinicum Freiburg, Freiburg, Germany) hyper-IgE recurrent infection syndrome (according to OMIM (Online Mendelian Inheritance in Man) naming, phenotype MIM (Mendelian Inheritance in Man) number #243700) 1 year ago when she presented with herpes simplex virus lesions disseminated throughout her body. Family history showed female and male patient deaths due to severe herpes simplex virus and human papillomavirus infections who died without receiving a genetic diagnosis (Figure 1, III-5e7). The patient was admitted with complaints of a swelling and wound on her lip which was under antifungal and antibiotic prophylaxis. The lip wound had begun as a herpetic lesion 7 months previously, and intravenous acyclovir was applied for 50 days by a regional clinic after progression of the lesion despite topical treatment. Foscarnet had been initiated

Epidemiological Profile of Cleft Lip and Palate Patients Attending Tertiary Care Hospital and Medical Research Centre, Belgaum, Karnataka–A Hospital Based Study

Cleft Lip and/or Palate (CL±P) is the most common congenital malformation of the face and its pattern varies with geography worldwide. Pattern and magnitude remains uncertain due to very few studies. This study has been conducted to study the epidemiological profile of CL±P patients attending a Tertiary Care Hospital & Medical Research Centre, Karnataka, India. This study includes 2453 CL±P Patients registered from 2007-2012 in the Department of Plastic and Reconstructive Surgery of this Hospital & Medical Research Centre. Data were collected from January to September 2013. Variables like age, sex, socioeconomic status, cleft pattern, birth order and consanguinity were noted. Associations of clefts with different variables were studied using Chi-square test. Among all cleft cases, 55.7% were males and 44.3% were females. Age of patients at presentation ranged from 1 day to 71 years with a median age of 2 years. Cleft Lip, Cleft Lip-Palate, Cleft Palate and rare clefts were noted in 21.7%, 61.1%, 16% and 1.1% cases, respectively. Family history was present in 1.3% cases. Consanguineous marriage was noted in 48.9% parents. 54.6% had income of less than Rs 5000 per month. 77% cases were first and second born child. Prevalence of CL±P was significantly higher in children of consanguineous parents (p<0.0001).

A case of Griscelli syndrome

A hallmark of Griscelli syndrome, a rare autosomal recessive disorder, is hair hypopigmentation characterized by a silver-gray sheen and the presence of large clusters of pigment unevenly distributed in the hair shaft. Either a primary neurological impairment or immune abnormalities are associated with this phenotype. We report the case of a 10-year-old child of consanguineous parents. He presented with abdominal pain and fever and was noted to have silvery hair, eyelashes, and eyebrows. Bone marrow studies indicated hemophagocytosis, whilst microscopic examination of the hair showed irregular agglomerations of pigment in hair shafts. The prognosis, treatment, and genetic counseling needs differ considerably among the various forms of Griscelli Syndrome.

Fraser Syndrome: case report in lacrimal system

Fraser syndrome is a systemic condition characterized by cryptophthalmos, syndactyly and abnormal genitalia, which may be associated with urinary tract, ear, nose, larynx and skeletal abnormalities. Cryptophthalmos can be an isolated finding (that has been reported as an autosomal dominant trait) or associated with other congenital anomalies (reported as an autosomal recessive disorder). Child, female, nine month of life, evaluated in the lacrimal setor of Federal University of São Paulo. Child of consanguineous parents. Her physical examination showed total unilateral [...]

Craniodentofacial Manifestations in a Rare Syndrome: Orofaciodigital Type IV (Mohr-Majewski Syndrome).

Background. The orofaciodigital syndromes (OFDS) are a heterogeneous group of syndromes that affect the face, oral cavity, and the digits. OFDS type IV (OMIM %258860) is rare and characterized by broad nasal root and tip, orbital hypertelorism or telecanthus, micrognathia, hypoplastic mandible, and low-set ears. Oral symptoms may include cleft lip, cleft or highly arched palate, bifid uvula, cleft or hypoplastic maxillary and mandibular alveolar ridge, oral frenula, lingual hamartoma, and absent or hypoplastic epiglottis. Dental anomalies are common and generally include disturbances in the number of teeth. Case Report. This report presents a six-year-old girl, referred with the chief complaint of missing teeth. She was diagnosed as having OFDS type IV based on clinical findings. Her parents reported three deceased children and two fetuses that had the same phenotype. She was the seventh child of consanguineous parents who were first cousins. Conclusion. This is a very rare syndrome. Many reported OFDS type IV cases have consanguineous parents, consistent with an autosomal recessive trait. Manifestation of cleft palate in the healthy sibling may be mild expression of the disorder or an unrelated isolated cleft.