Sparse Hair Research Articles

A novel homozygous synonymous variant further expands the phenotypic spectrum of POLR3A‐related pathologies

Pathogenic biallelic variants in POL3RA have been associated with different disorders characterized by progressive neurological deterioration. These include the 4H leukodystrophy syndrome (hypomyelination, hypogonadotropic hypogonadism, and hypodontia) and adolescent-onset progressive spastic ataxia, as well as Wiedemann-Rautenstrauch syndrome (WRS), a recognizable neonatal progeroid syndrome. The phenotypic differences between these disorders are thought to occur mainly due to different functional effects of underlying POLR3A variants. Here we present the detailed clinical course of a 37-year-old woman in whom we identified a homozygous synonymous POLR3A variant c.3336G>A resulting in leaky splicing r.[3336ins192, =, 3243_3336del94]. She presented at birth with intrauterine growth retardation, lipodystrophy, muscular hypotonia, and several WRS-like facial features, albeit without sparse hair and prominent scalp veins. She had no signs of developmental delay or intellectual disability. Over the years, above characteristic facial features, she showed severe postnatal growth retardation, global lipodystrophy, joint contractures, thoracic hypoplasia, scoliosis, anodontia, spastic quadriplegia, bilateral hearing loss, aphonia, hypogonadotropic hypogonadism, and cerebellar peduncles hyperintensities in brain imaging. These manifestations partially overlap the clinical features of the previously reported POLR3A-associated disorders, mostly mimicking the WRS. Thus, our study expands the POLR3A-mediated phenotypic spectrum and suggests existence of a phenotypic continuum underlying biallelic POLR3A variants.

Two zinc-finger proteins control the initiation and elongation of long stalk trichomes in tomato

Plant glandular trichomes are epidermal secretory structures that are important for plant resistance to pests. Although several regulatory genes have been characterized in trichome development, the molecular mechanisms conferring glandular trichome morphogenesis are unclear. We observed the differences in trichomes in cultivated tomato cv. ‘Moneymaker’ (MM) and the wild species Solanum pimpinellifolium PI365967 (PP), and used a recombinant inbred line (RIL) population to identify the genes that control trichome development in tomato. We found that the genomic variations in two genes, HAIR (H) and SPARSE HAIR (SH), contribute to the trichome differences between MM and PP. H and SH encode two paralogous C2H2 zinc-finger proteins that function redundantly in regulating trichome formation. Loss-of-function h/sh double mutants exhibited a significantly decreased number of Type I trichomes and complete loss of long stalk trichomes. Molecular and genetic analyses further indicate that H and SH act upstream of ZFP5. Overexpression of ZFP5 partially restored the trichome defects in NIL-hPPshPP. Moreover, H and SH expression is induced by high temperatures, and their mutations inhibit the elongation of trichomes that reduce the plant repellent to whiteflies. Our findings confirm that H and SH are two vital transcription factors controlling initiation and elongation of Type I and III multicellular trichomes in tomato.

Prosthetic rehabilitation of a hypohidrotic ectodermal dysplasia patient: A case report

Aim: Ectodermal dysplasia is a rare hereditary disease that arises from a developmental disorder of 2 or more ectoderm-derived tissues. Ectodermal dysplasia is seen in 3 different types: anhidrotic, hypohidrotic, and hidrotic. Its anhidrotic and hypohidrotic types are the most common. This study presents the intraoral findings and dental treatment approach of a case diagnosed with hidrotic ectodermal dysplasia that demonstrates the typical characteristics of the disease, such as anodontia, hypohydrosis (reduced sweating), hypotrichosis (sparse hair), and loss of vertical dimension.
 Methodology: A 5-year-old male patient presented to the clinic of the Prosthetic Dental Treatment Department of the School of Dentistry at Dicle University on 25.10.2020 with complaint of missing teeth. A genetic analysis conducted in 2016 showed that he was a homozygous carrier of the p.Cys148Arg (c.442 T>C) mutation on the 5th exon of the ectodysplasin-A receptor (EDAR) gene. The mutation detected in the patient was associated with ectodermal dysplasia. An extraoral clinical examination revealed sparse hair, eyebrows, and eyelashes; soft, smooth, and dry skin; thin, linear wrinkles around the eyes and the lips; drooping, thickened lips; a sunken nose; fractured nails; hyperthermia due to lack of sweat glands; hyperkeratosis in the skin and soles of the feet; 2 nipples on one side of the chest; and reduced vertical facial height. An intraoral examination revealed anodontia; there were no teeth on the maxilla or the mandible and no radiographically identified tooth germ. Dry mouth due to a lack of sufficient saliva was another finding.
 Conclusion: In this case report, in the presence of anodontia, a removable total prosthesis, which is a non-invasive treatment option, was applied. Production of endosseous implants was postponed for a later time following the patient’s growth and development.
 
 How to cite this article: Gökçe D, Ayna E, Seyfioğlu Polat Z. Prosthetic rehabilitation of a hypohidrotic ectodermal dysplasia patient: A case report. Int Dent Res 2021;11(Suppl.1):292-8. https://doi.org/10.5577/intdentres.2021.vol11.suppl1.43
 
 Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.

Carasil and htra1: an early adulthood syndrome

Cerebral Autosomal Recessive Arteriopathy Subcortical Infracts Leukoencephalopathy (CARASIL), is an autosomal recessive disorder inherited by two copies of an abnormal gene from some trait, one from each parent. Person with this disorder may have a change in deep white matter in brain; and this disorder can be characterized by damage to small blood vessels in brain. Increasing muscle tone, slurred speech, stiff movement of legs, gait disturbance, spondylosis, sparse hair are the major symptoms. But the ultimate cause of this disorder can lead to loss of memory, cognitive impairment. This disorder can be caused in early adulthood i.e., between 20-40 years of age. CARASIL has first reported in Japan, later occurred in China and Caucasian population. A neurological disorder named Binswanger’s disease (BD) and chronic immunological disorder multiple sclerosis are main different alternation of this disease. Mutation requires the high temperature resultant, A serine peptidase 1 causes CARASIL, so it is a serine protease.
 Serine protease HTRA1 is an enzyme that in humans is encoded by HTRA1 gene. HTRA1 protein is composed of four distinct protein domains. This is located on the long (q) arm of chromosome 10 in a region known as 10q26. This protein is a secreted enzyme that is proposed to regulate the availability of insulin like growth factors (IGF) by cleaving IGF binding proteins. HTRA1 enzyme helps breakdown many other kinds of proteins in this space surrounding cells (extracellular matrix). This is attached to protein in Transforming Growth Factor Beta (TGF-beta) and slows down their ability to send chemical signals. Variant known as rs11200638 is found in an area of gene called promoter region which starts the production HTRA1 enzyme. It is unclear how of polymorphism in the HTRA1 gene might be an age-related macular degeneration.
 So at last, we can conclude that CARASIL is related to brain inherited from the abnormal genes caused to small arteries and to the specific area of deep brain in higher function; tissue loss due to lack of oxygen where small arteries get blocked destruction to myelin an oily substance covers and protects the nerve fibers in CNS.

Novel missense mutation of the TP63 gene in a newborn with Hay-Wells/Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome: clinical report and follow-up

IntroductionAnkyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare genetic syndrome with ectodermal dysplasia. About 100 patients have been reported to date. It is associated to a heterozygous mutation of the tumor protein p63 (TP63) gene, located on chromosome 3q28. Typical clinical manifestations include: filiform ankyloblepharon adnatum (congenital adherence of the eyelids), ectodermal abnormalities (sparse and frizzy hair, skin defects, nail alterations, dental changes and hypohidrosis), and cleft lip/palate. Diagnostic suspicion is based on clinical signs and confirmed by genetic testing.Patient’s presentationWe hereby report on a female newborn with erythroderma, thin lamellar desquamations, extensive skin erosions, sparse and wiry hair, filiform ankyloblepharon adnatum, agenesis of the lachrymal puncta, cleft palate and nail dysplasia. Her phenotype was compatible with AEC syndrome. Then, based on the clinical suspicion, sequencing analysis of the TP63 gene was performed, and revealed a de novo novel missense mutation. Eyelids adherence and cleft palate underwent surgical correction, while skin erosions were treated with topical antibiotics/antifungals and emollient/re-epithelizing creams. A surgical reconstruction is presently planned for the agenesis of the lachrymal puncta. The infant currently is 17 months of age and is included in a multidisciplinary follow-up. At present shows growth impairment and mild developmental delay, and typical signs of ectodermal dysplasia with small areas of dermatitis lesions on the scalp, without further abnormalities.ConclusionsOur report underlines the relevance of an early and careful clinical evaluation in neonates with ankyloblefaron, facial dysmorphism, and signs of ectodermal dysplasia. In these cases, the suspicion of AEC syndrome must be promptly raised, and sequencing analysis of TP63 early performed as well. An individualized, multidisciplinary and long-term follow-up should be guaranteed to affected subjects and their families, also to identify associated morbidities and prevent possible serious complications and adverse outcomes.

Recurrent Fevers in a Boy Toddler with Dysmorphic Features and Hypodontia.

Recurrent Fevers in a Boy Toddler with Dysmorphic Features and Hypodontia.

Four hypotrichosis families with mutations in the gene LSS presenting with and without neurodevelopmental phenotypes.

Four hypotrichosis families with mutations in the gene LSS presenting with and without neurodevelopmental phenotypes.

Molecular basis of ectodermal dysplasia

Ectodermal dysplasia (ED) syndrome is a rare genetic disease that involves a heterogeneous group of hereditary disorders that occur as a result of mutations in genes that code for development of fetal ectoderm and lead to numerous disorders. Defects in the development of the ectoderm cause symptoms in tissues derived from the ectoderm layer, such as skin, nails, hair, and teeth. Because many pathways are involved in the development of the ectoderm, there are mutations in many genes that cause ED. Owing to the heterogeneity of ED, there are different types of the disease that have different symptoms. These symptoms include sparse hair, abnormal or missing teeth, nail dystrophy, lack of sweating owing to the absence of sweat glands, and cancer. In this review, in addition to discussing the role and pathway of each of the genes involved in ED, the incidence of cancer in these patients, diagnostic methods and differentiation from other similar diseases, and the treatments currently being performed for ED are discussed.

Novel pathogenic variants in the RECQL4 gene causing Rothmund‐Thomson syndrome in three Chinese patients

Rothmund-Thomson syndrome (RTS) is a rare autosomal-recessive disorder characterized by poikiloderma, short stature, sparse hair, skeletal abnormalities, and cancer predisposition. Mutations in ANAPC1 or RECQL4 have been identified to underlie RTS. Either Sanger sequencing or next-generation sequencing (NGS) was performed for three Chinese RTS patients. Copy number variants were called by the eXome-Hidden Markov Model using read-depth data of NGS, and the putative heterozygous deletion was confirmed by PCR with multiple primers. The breakpoints were identified by Sanger sequencing. All patients presented with characteristic features of poikiloderma, short stature, and sparse hair, eyelashes, and eyebrows. In addition, patient 1 had intellectual disability and speech delay, and patient 2 developed osteosarcoma when she was 13years old. Biallelic RECQL4 variants were identified in all three patients. Five of the six variants were novel, including c.119-1G>A, c.2886-1G>A, c.2290C>T (p.Gln764*), and c.3552dupG (p.Arg1185Glufs*42), and a gross deletion encompassing exons 6 to 10. Our study expands the genetic and clinical spectrums of RTS. Furthermore, we reported the first heterozygous gross deletion in RECQL4.

NAD(P)HX dehydratase (NAXD) deficiency due to a novel biallelic missense variant and review of literature

Encephalopathy, progressive, early-onset, with brain edema and/or leukoencephalopathy, 2 (PEBEL2; MIM# 618321), caused by biallelic pathogenic variants in the NAD(P)HX dehydratase (NAXD) is a rare metabolite repair disorder. It is characterized by progressive neurological deterioration usually associated with a febrile illness. The other common findings include skin lesions, elevated serum or cerebrospinal fluid lactate levels, and brain neuroimaging abnormalities. Currently, variants in NAXD have been reported in eight unrelated individuals including six truncating and six missense variants. We report on an additional individual with characteristic findings of PEBEL2, and an additional finding of sparse scalp hair. A novel missense variant c.301G > A, p.(Ala101Thr) in a homozygous state was identified through exome sequencing. This study adds to the phenotypic and mutational spectrum of PEBEL2. We review the existing phenotypic and genotypic information for the individuals with this neurometabolic condition.

Genotype-Phenotype Correlations in 208 Individuals with Coffin-Siris Syndrome.

Coffin-Siris syndrome (CSS, MIM 135900) is a multi-system intellectual disability syndrome characterized by classic dysmorphic features, developmental delays, and organ system anomalies. Genes in the BRG1(BRM)-associated factors (BAF, Brahma associated factor) complex have been shown to be causative, including ARID1A, ARID1B, ARID2, DPF2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, and SOX4. In order to describe more robust genotype-phenotype correlations, we collected data from 208 individuals from the CSS/BAF complex registry with pathogenic variants in seven of these genes. Data were organized into cohorts by affected gene, comparing genotype groups across a number of binary and quantitative phenotypes. We determined that, while numerous phenotypes are seen in individuals with variants in the BAF complex, hypotonia, hypertrichosis, sparse scalp hair, and hypoplasia of the distal phalanx are still some of the most common features. It has been previously proposed that individuals with ARID-related variants are thought to have more learning and developmental struggles, and individuals with SMARC-related variants, while they also have developmental delay, tend to have more severe organ-related complications. SOX-related variants also have developmental differences and organ-related complications but are most associated with neurodevelopmental differences. While these generalizations still overall hold true, we have found that all individuals with BAF-related conditions are at risk of many aspects of the phenotype, and management and surveillance should be broad.

CASE REPORT: REPORTING THE ORO-DENTAL FINDINGS OF ELLIS-VAN CREVELD SYNDROME – A RARE GENETIC DISORDER

<h3>Introduction</h3> Ellis-van Creveld syndrome (EVC) is a rare autosomal recessive disorder, which is also known as chondroectodermal dysplasia. It is caused by genetic mutation in 2 genes: EVC1 and EVC2. The syndrome has a rare occurrence with a prevalence of 1 in 60,000 to 200,000 worldwide. EVC consists of a distinctive tetrad of various clinical manifestations: chondrodysplasia of tubular bones leading to dwarfism, polydactyly plus syndactyly, ectodermal dysplasia comprising of sparse hair together with dystrophic nails, and congenital morbus cordis commonly involving the single atrium and ventricular septal defect. In addition to the characteristic features, EVC also consists of a unique set of oral manifestations. The present case discusses the various oro-dental findings in a young patient of this rarely reported syndrome. <h3>Case Report</h3> A 7-year-old male patient visited Jinnah Sindh Dental Outpatient Department with a complaint of missing maxillary anterior teeth. In the present case, the patient had a history of consanguineous marriage of parents, supporting the recessive nature of the disorder. <h3>General Examination</h3> The general examination showed that the patient had disproportionate short stature. The limbs were short with postaxial polydactyly affecting both hands. The nails were thin and dystrophic. Other findings were hypertelorism and broad depressed nasal bridge. <h3>Oral Examination</h3> The oral examination revealed absence of mandibular anterior mucobuccal fold, mandibular hyperplastic frenula, labiogingival adhesions, serrated appearance of the gingiva, and morphological abnormalities of mandibular anterior teeth with prominent diastema. The maxillary incisors were absent. Multiple frenulum and attaching labial mucosa to alveolar mucosa were also observed.

Isolated autosomal recessive woolly hair/hypotrichosis: genetics, pathogenesis and therapies.

Isolated autosomal recessive woolly hair/hypotrichosis (ARWH) is a rare hereditary hair disease characterized by tightly curled sparse hair at birth or in early infancy. Patients with ARWH consist of genetically heterogeneous groups. Woolly hair autosomal recessive 1 (ARWH1) (MIM #278150), woolly hair autosomal recessive 2 (ARWH2) (MIM #604379) and woolly hair autosomal recessive 3 (ARWH3) (MIM #616760) are caused by mutations in LPAR6, LIPH and KRT25, respectively. In addition, nonsense variants in C3ORF52 (*611956) were identified in ARWH patients. The frequencies of the mutations in the causative genes in ARWH patients are thought to differ by ethnicity and country/geographical area. Large numbers of ARWH families with LIPH mutations have been described only in populations from Japan, Pakistan and the Volga-Ural region of Russia. In that region of Russia, most ARWH families have an extremely prevalent founder mutation, the deletion of exon 4, in LIPH. In the Pakistani population, 47.2% of ARWH families had the disease due to LIPH mutations and 52.8% of them carried LPAR6 mutations. The prevalent, recurrent LIPH mutation c.659_660delTA (p.Ile220Argfs*29) was found in more than half of Pakistani ARWH families with LIPH mutations. Most Japanese ARWH families (98.7%) harbour LIPH mutations, including the two highly prevalent, recurrent LIPH mutations c.736T>A (p.Cys246Ser) and c.742C>A (p.His248Asn). In ARWH patients whose disease was due to LIPH, LPAR6 or C3ORF52 mutations, the loss of function of LIPH, LPAR6 or C3ORF52 leads to reduced LIPH-LPA-LPAR6 signalling, resulting in the decreased transactivation of EGFR signalling and the phenotype of underdeveloped hairs. Our recent prospective interventional study suggests that topical minoxidil might be a promising treatment for ARWH due to LIPH mutations, although sufficiently effective treatments have not been established for ARWH yet.

Homozygous ITGA3 Missense Mutation in Adults in a Family with Syndromic Epidermolysis Bullosa (ILNEB) without Pulmonary Involvement

Homozygous ITGA3 Missense Mutation in Adults in a Family with Syndromic Epidermolysis Bullosa (ILNEB) without Pulmonary Involvement

Endophytic fungi in blueberry cultivars, in three production areas of Argentina

Blueberries develop a shallow and fibrous root system, with sparse root hairs, normally colonized by mycorrhizal fungi. The presence of endophytic fungi in blueberry roots has been studied mainly in the area of origin of each species. The aims of the present study were to determine the occurrence of endophytic fungi in the roots of southern highbush blueberry (SHB) cultivars, in the three most important blueberry production areas of Argentina, and identify them. Soil samples with blueberry rootlets were obtained and endophytic fungi were isolated from them. Some of them by classical taxonomy identification, and, when this was not possible, PCR amplified material were sequenced (Macrogen laboratory), DNA fragments were analyzed with the Basic Local Alignment Search Tool (BLAST) and identified, through GenBank. Blueberry roots were found to be colonized by a large number of fungal genera, which varied greatly among locations and cultivars. Some of the endophytic fungi identified have pathogenic function, others are only plant hosts, and some of them have mycorrhizal function as is the case of genus Oidiodendron where we found O. maius and O. echinulatum. We may conclude that SHB is associated with local ericoid fungi, some of which are mycorrhizal and some dark septate endophytes, which, in most cases, do not match with those found in production regions of their native area, but same of them are important to promote blueberry growth.

A Novel Homozygous WRN Mutation Identified in a Middle Aged Man With Diabetes Mellitus Complicated By Multiple Features of Accelerated Aging

Background: Werner syndrome (WS; MIM# 277700) is a rare genetic disorder characterized by accelerated aging and predisposition to cancers. The causal gene, WRN, encodes a multifunctional nuclear protein that belongs to the RecQ family of DNA helicases. The earliest sign of WS is short stature due to the lack of pubertal growth spurt. In addition to the aged-appearance, WS patients typically develop functional declines of multiple organs including the endocrine system in their middle ages. Frequent Endocrine disorders include Type 2 Diabetes (T2D), dyslipidemia (DL), hypothyroidism, hypogonadism and osteoporosis. Most common causes of deaths are myocardial infarction and cancers in their 50s. Clinical Case: A 54-year old man was admitted for right wrist septic arthritis. His medical history was pertinent for premature cataract diagnosed in his 2nd decade. He had uncontrolled T2D (peak HbA1C level 10%) since the age of 32 years, treated with oral hypoglycemics including glimepiride, sitagliptin and metformin then shifted to insulin over the past 2 years. He also had DL since the age of 41 years, characterized by hypertriglyceridemia (766 mg/dL) with very low HDL (7 mg/dL). At age 50, he was diagnosed with hypothyroidism and negative anti-TPO antibodies. Moreover, he had refractory bilateral leg ulcers that manifested at the age of 35 years requiring multiple debridments, premature coronary artery disease at the age of 38 years and ischemic cardiomyopathy. On examination, his height was 154 cm and weight 42 kgs. He had prominent eyes, a pinched nose, grey and sparse scalp hair with absence of eyebrows and eyelashes. Hoarse voice was easily noticeable. He had very thin limbs, flat feet, central fat distribution and muscle wasting. Skin was shiny, tight, and atrophic with overlying hypermelanosis. Old bilateral hyperkeratotic deep feet ulcers were noticed with variable necrosis. Blood chemistry testing showed: HbA1C 8.2%, disturbed lipid profile, TG 341 mg/dL, HDL 17 mg/dL, LDL 155 mg/dL, and TSH 21 µU/mL (0.2 - 4.2 µU/mL). MRI of the foot revealed Achilles’ tendon calcification. His parents were 2nd degree cousins and had normal features. Three of his siblings had similar features and premature death. His diabetes was atypical due to his low BMI, high insulin requirements and the relatively early onset. WS was suspected based on the overall features of accelerated aging with characteristic deep leg ulcers and the family history. Genetic sequence analysis revealed a novel pathogenic homozygous nonsense variant mutation c.1111G>T, p.Glu371* of the WRN gene. Conclusion: Werner syndrome is a rare genetic disease, but it carries high morbidity and mortality burden, in addition to impaired quality of life. It should be highly suspected in patients with atypical T2D, DL, premature coronary disease, refractory leg ulcers with features of accelerated aging and short stature.

Two new species of Euphaea Selys, 1840 (Odonata: Zygoptera: Euphaeidae) from northern Western Ghats, India

Two new species of the damselfly genus Euphaea Selys, 1840 (Odonata: Euphaeidae) are described from the Western Ghats of Satara District, Maharashtra, distinguished by their distinct morphology and coloration. E. thosegharensis Sadasivan &amp; Bhakare sp. nov. is similar to E. cardinalis (Fraser, 1924), but is distinguished by the extensor and flexor surface of all femora black while all femora bright red in E. cardinalis; apical fourth of Hw black while apical half of Hw black in E. cardinalis; genae reddish-orange, black in E. cardinalis; a tuft of sparse stub black hair on either side of tergite of S9 while both S8 and S9 with tufts of long ventral hairs in E. cardinalis. Male genital vesicle matt black, with distal border rounded angles, while vesicle black and hexagonal in shape with rounded angles in E. cardinalis and S9 twice the length of S10, while S9 and S10 of equal length in E. cardinalis. E. pseudodispar Sadasivan &amp; Bhakare sp. nov., is very close to E. dispar (Rambur, 1842), but is differentiated easily by the absence of yellow patch on legs as in E. dispar; only apical fifth of Hw black; genae being yellowish-white, while black in E. dispar; male genital vesicle brownish-black &amp; rhomboid-shaped and with no transverse rugosities while black with distal border rounded and with fine transverse rugosities in E. dispar; penis with single seta on each side while E. dispar has three pairs; sternite of S9 very prominently extending ventrally like a beak in comparison with E. dispar. We have identified additional morphological characters useful in taxonomy of Euphaea of the Western Ghats for example, tufts of ventral hairs on terminal abdominal segments genital vesicle, penile structure of males and sternite of S9 in the males, and vulvar scales of females. A taxonomic key to all known species of genus Euphaea of the Western Ghats is also provided.

Hypotrichosis‐lymphedema‐telangiectasia syndrome: Report of ileal atresia associated with a SOX18 de novo pathogenic variant and review of the phenotypic spectrum

Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is a rare condition caused by pathogenic variants in the SOX18 gene. SOX18 plays a key role in angio- and lymphangiogenesis due to its expression in venous endothelial cells from which the lymphatic system develops. It is also expressed in embryonic hair follicles, heart, and vascular smooth muscle cells. The main clinical symptoms of HLTS include sparse hair, alopecia totalis, lymphedema, most often affecting lower limbs, and telangiectatic lesions. Only 10 patients with a SOX18 pathogenic variant have been described that presented with additional features such as hydrocele, renal failure, arterial or pulmonary hypertension, aortic dilatation, and facial dysmorphism. Here, we summarize these phenotypic variations and report an additional HLTS patient, with a 14-nucleotide de novo duplication in SOX18 and congenital ileal atresia, a feature not previously associated with HLTS.

Pregnancy in a patient with Rothmund-Thomson type 2 syndrome.

Rothmund-Thomson syndrome (RTS; MIM#268400) is an autosomal recessive genodermatosis with <500 cases described in the literature [1]. About 60% of RTS cases carry biallelic pathogenic variants in the RECQL4 gene representing the prevalent RTS subentity (RTS-2) [1]. RTS-2 is characterized by poikiloderma manifesting in the first months of life on photo-exposed areas, short stature, sparse hair, eyelashes and/or eyebrows, skeletal abnormalities, and predisposition to malignancy [1]. Endocrine signs may be present and subfertility is common; however, a few patients have had healthy offspring [2-3].

Acrocephalosyndactyly Syndrome: A Rare Case Report

Acrocephalosyndactyly or Apert syndrome is a rare disorder in which the fingers and toes are fused,giving the appearance of webbed hand and feet. Also, there is craniosynostosis, leading to severe mid-facehypoplasia and characteristic facial deformities. Here there is a genetic mutation in the fibroblast growthfactor receptor 2 (FGFR2) gene with autosomal dominant inheritance. A case of an 8-year-old male child isreported here with frontal bossing, acrocephaly, prominent ocular hypertelorism with divergent strabismus,saddle-shaped nose, mid-face hypoplasia, crowded anterior teeth, sparse hair and severe bilateral syndactylyof the feet and hands.