Absent Eyebrows Research Articles

Whitaker syndrome: A case report of autoimmune polyendocrine syndrome type 1 with dilated cardiomyopathy.

This case report highlights dilated cardiomyopathy as a cardiovascular complication in autoimmune polyendocrine syndrome type 1 (APS-1), emphasizing the need for early recognition and a multidisciplinary approach. Comprehensive care and regular follow-up are crucial in managing these atypical presentations to optimize patient outcomes. APS-1, also known as Whitaker syndrome, is characterized by a triad of mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. This rare autosomal recessive disorder results from mutations in the autoimmune regulator (AIRE) gene. Cardiovascular and pulmonary manifestations in APS-1 are infrequently reported in the literature. We present a case of a 28-year-old male who presented with shortness of breath and pedal edema. Physical examination revealed alopecia, absence of eyebrows, hyperpigmentation on joints, oral candidiasis, and nail dystrophy. Echocardiography demonstrated dilated cardiomyopathy (DCM) and pericardial effusion. Chest x-ray showed left-sided pleural effusion. Laboratory investigations revealed hypocalcemia, hyperphosphatemia, low parathyroid hormone (PTH), low cortisol, and high adrenocorticotropic hormone (ACTH) levels. The combination of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency confirmed the diagnosis of APS-1. To the best of our knowledge, this is the first Pakistani and second worldwide reported case of APS-1 presenting with such a combination of manifestations. Early recognition and multidisciplinary management are crucial for improving outcomes in these patients.

Arousal and valence have dissociable effects on responses to schematic emotional faces.

Studies examining behavioural responses to emotional stimuli usually report one of two patterns of responses to negative stimuli. Some studies find faster responses to negative material. Other studies find slower responses to negative stimuli. While the attentional mechanisms proposed to explain these findings (attentional capture in the former case, delayed disengagement in the latter) are not at odds with one another, the behavioural findings do need to be reconciled. We posit that arousal, being the primary differentiator of threatening and nonthreatening stimuli, needs to be more carefully considered. To this end, two experiments were conducted evaluating the role of stimulus arousal and valence in the processing of schematic emotional faces. In Experiment 1, stimulus arousal was manipulated via the presence or absence of eyebrows in the schematic faces in a faces flanker task. Results showed faster responses to faces with eyebrows but no differences in the faces flanker asymmetry between faces with and without eyebrows. In Experiment 2, participants rated the faces on an evaluative space grid. Results showed the presence of the eyebrows had a greater impact on negative ratings for negative faces than for the other expressions. This suggests that stimulus valence and arousal were manipulated by the eyebrows and the reaction time differences could not be attributed purely to perceptual differences. Together these results suggests that both valence and arousal impact the processing of emotional schematic faces, and that these effects are dissociable. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A-318 Pseudo-hypertriglyceridemia in a 2-year-old Male with Global Developmental Delay, Myopathy and Adrenal Hypoplasia

Abstract Background Pseudo-hypertriglyceridemia is an overestimation of serum triglyceride levels due to laboratory assays that measure free glycerol concentrations instead of triglycerides directly. Consequently, conditions presenting with elevated levels of endogenous or exogenous free glycerol, such as glycerol kinase deficiency, result in an overestimation of serum triglycerides. Glycerol kinase deficiency (GKD) is caused by pathogenic variants of the GK gene on chromosome Xp21. Three forms of GKD are recognized, characterized as infantile, juvenile, and adult forms. While the juvenile and adult forms are recognized as isolated GKD, the infantile form manifests itself as part of the Xp21.3 contiguous gene deletion syndrome, also known as complex GKD. This syndrome is composed of genes associated with Duchenne muscular dystrophy (DMD), X-linked congenital adrenal hypoplasia (NR0B1), and intellectual disability (IL1RAPL1). GKD is characterized biochemically by hyperglycerolaemia and glyceroluria. Case Description A 2-year-old male presented to the genetics clinic with a history of global developmental delay (gross motor and speech), axial hypotonia, poor head control and inability to sit unassisted or walk. Significant findings on examination included a startled appearance, absent eyebrows and temporal thinning, high forehead, frontal bossing, axial hypotonia and peripheral hypertonia. Laboratory findings included elevated creatine kinase (CK) of 14809 units/L (normal 27–160 units/L), aspartate aminotransferase (AST) of 307 (normal 20–60 units/L), alanine aminotransferase (ALT) 265 (normal 15–45 units/L), Adrenocorticotropic Hormone (ACTH) 156 (normal 6–48 pg/mL), and elevated triglycerides at 683 (normal 44–157 mg/dL). There was also a family history of developmental delay and intellectual disability in patient's mother and younger sister. Method Triglycerides are commonly measured indirectly with different enzyme reagents. The Triglycerides in this boy were measured by an automated chemistry analyzer based on a colorimetric serial enzymatic reaction including lipase, glycerol kinase and L-α-glycerol-phosphate oxidase1. Urinary organic acids profile including glycerol was extracted from acidified urine (pH 1-2) using diethyl ether. Organic extracts are then evaporated to dryness under nitrogen and trimethysilyl derivatized by the addition of N, O-bis (trimethylsilyl) trifluoroacetamide with 1% trimethylchorosilane (BSTFA/TMCS) and analyzed by gas chromatography-mass spectrometry (GC-MS). Results A comprehensive work-up including qualitative urinary organic acid analysis and chromosomal microarray was carried out. Urinary organic acids analysis revealed very abnormal accumulation of glycerol. Chromosomal microarray results showed a 4.2 Mb deletion of Xp21.3p21.1 (29296579-33551038) including complete copies of GK, DMD, and NR0B1 genes as well as multiple exons of IL1RAPL1. This confirmed his GKD as part of the Xp21 continuous gene deletion syndrome. Elevated triglycerides were then recognized as pseudo-hypertriglyceridemia after the diagnosis. Mild glyceroluria is also observed in the younger sister of this patient. Discussion and Conclusion This case highlights the importance recognizing pseudo-hypertriglyceridemia and diagnostic challenges. Earlier identification through urine organic acid analysis could have been made. The combination of clinical presentations and increased glycerol should cause suspicion for GKD. Female carriers of this X-linked disorder need to be evaluated for intellectual disability, as seen in this patient's mother and younger sister.

Molecular and phenotypic spectrum of cardio-facio-cutaneous syndrome in Chinese patients

BackgroundCardio-facio-cutaneous (CFC) syndrome is a RASopathy subtype that presents with unique craniofacial dysmorphology, congenital heart disease, dermatologic abnormalities, growth retardation, and intellectual disability. This study describes the phenotypic spectrum of CFC in China and its association with CFC syndrome gene variants.ResultsTwenty Chinese CFC patients, aged 0.6–9.5 years old, were included in this study and their clinical phenotypic spectrum was compared with that of 186 patients with CFC from non-Chinese ethnicities. All 20 Chinese patients with CFC carried de novo heterozygous BRAF, MAP2K1, and MAP2K2 variants. Two novel variants were detected and consistently predicted to be deleterious using bioinformatic tools. The clinical features of CFC in the Chinese patients included hypertrophic cardiomyopathy (2/20, 10%), pulmonary valve stenosis (2/20, 10%), curly or sparse hair (7/20, 35%), epilepsy (1/20, 5%), and hypotonia (10/20, 50%); these features were less frequently observed in Chinese patients than non-Chinese patients (p < 0.05). In contrast, feeding difficulties (19/20, 95%) were more frequently observed in the Chinese patients. Absent eyebrows and severe short stature were more common in patients with BRAF variants than in those with MAP2K1/2 variants. Facial recognition software was used to recognize most CFC patients using artificial intelligence.ConclusionThis study identified novel and common variants in our cohort of 20 Chinese patients with CFC. We uncovered differences in clinical features between Chinese and non-Chinese patients and detected genotype–phenotype correlations among the BRAF and MAP2K1/2 variant subgroups. This is the largest cohort of Chinese CFC patients to our knowledge, providing new insights into a subtype of RASopathy.

Eyebrow Reconstruction in Craniofacial Clefts by Abnormal Hairline Extention.

The absence of eyebrows, whether complete or partial, has been observed in specific types of craniofacial clefts, primarily occurring in Tessier clefts numbers 9 to 13. To address this defect, several techniques have been used to improve eyebrow appearance, such as the island scalp flap and scalp strip grafting technique. However, these methods did not yield satisfactory esthetic results. In this study, the authors present findings from 7 patients with craniofacial clefts, in whom the eyebrows were completely reconstructed through the rotation flap technique, using abnormal frontal hairline extension, in 1 or 2 stages. The result was natural-looking and highly satisfactory, with no associated morbidity.

BG01 Confirming small nuclear ribonucleoprotein polypeptide E as a cause of nonsyndromic hypotrichosis

Abstract Hereditary nonsyndromic hypotrichosis comprises at least 15 genetically distinct but phenotypically overlapping disorders. Affected individuals generally have hair at birth, which sheds during infancy or childhood. Severity ranges from partial alopecia to complete loss of scalp and body hair, with phenotypic variability between and within families. Genetic testing is essential for accurate diagnosis and counselling. We describe a case where several factors contributed to a delay in genetic diagnosis. A female child of nonconsanguineous White parents was born at term with normal hair that started to shed at 2 weeks of age. By 6 weeks of age, there was a complete absence of scalp, eyelash and eyebrow hair. There was no relevant family history apart from atopy. On examination at 3.3 years of age, she had total alopecia apart from some hairs in the external auditory canals. Nails, teeth and sweating were normal. She appeared developmentally normal and healthy apart from mild eczema with persistent erythema on both cheeks. The differential diagnosis included autoimmune alopecia and genetic nonsyndromic hypotrichosis. She was recruited to the 100 000 Genomes Project, but primary analysis did not identify any causative variants. Reanalysis using a limited gene-agnostic approach identified heterozygosity for the c.1A&amp;gt;G; p.(Met1?) variant in small nuclear ribonucleoprotein polypeptide E (SNRPE) that was not present in parents. This variant is not present in the gnomAD population database and is predicted to alter the initiation codon of SNRPE. It has been reported de novo in a British girl with sparse scalp hair and eyelashes and absent eyebrows, and in eight affected members of a Spanish family whose phenotypes ranged from sparse eyebrows and eyelashes to complete alopecia (Pasternack SM, Refke M, Paknia E et al. Mutations in SNRPE, which encodes a core protein of the spliceosome, cause autosomal dominant hypertrichosis simplex. Am J Hum Genet 2013; 92:81–7). This condition has been designated hypotrichosis type 11. SNRPE encodes a core protein of U small nuclear ribonucleoproteins, which are essential to the removal of introns from pre-mRNA and thus critical for the post-transcriptional modification of RNA. In our case, review of the primary analysis showed that the incorrect gene panel was applied (‘familial cicatricial alopecia’ instead of ‘nonsyndromic hypotrichosis’) and that SNRPE was listed as ‘amber’ for hypotrichosis, meaning ‘moderate evidence for this gene–disease association and should not yet be used for genome interpretation’. Genomics England has now incorporated nonsyndromic hypotrichosis into the ‘ectodermal dysplasia’ panel, with SNRPE now listed as ‘green’ for hypotrichosis 11, meaning a ‘high level of evidence for this gene–disease association’. This case emphasizes the importance of revisiting negative results as knowledge evolves.

A Rare Case of Ablepharon Macrostomia Syndrome

Ablepharon Macrostomia Syndrome (AMS) is a rare condition characterized by absent or extremely short eyelids and a large fish-like mouth, only 20 cases were reported. AMS is characterized by absent or short eyelids, absent eyebrows and eyelashes, macrostomia, and external ear abnormalities

Extended Overview of Ocular Phenotype with Recent Advances in Hypohidrotic Ectodermal Dysplasia.

The term ectodermal dysplasias (EDs) describes a heterogeneous group of inherited developmental disorders that affect several tissues of ectodermal origin. The most common form of EDs is hypohidrotic ectodermal dysplasia (HED), which is characterized by hypodontia, hypotrichosis, and partial or total eccrine sweat gland deficiency. HED is estimated to affect at least 1 in 17,000 people worldwide. Patients with HED have characteristic facies with periorbital hyperpigmentation, depressed nasal bridge, malar hypoplasia, and absent or sparse eyebrows and eyelashes. The common ocular features of HED include madarosis, trichiasis, and ocular chronic surface disease due to dry eye syndrome, which manifests clinically with discomfort, photophobia, and redness. Dry eye is common in HED and results from a combination of ocular surface defects: mucus abnormalities (abnormal conjunctival mucinous glands), aqueous tear deficiency (abnormalities in the lacrimal gland) and lipid deficiency (due to the partial or total absence of the meibomian glands; modified sebaceous glands with the tarsal plate). Sight-threatening complications result from ocular surface disease, including corneal ulceration and perforation with subsequent corneal scarring and neovascularization. Rare ocular features have been reported and include bilateral or unilateral congenital cataracts, bilateral glaucoma, chorioretinal atrophy and atresia of the nasolacrimal duct. Recognition of the ocular manifestations of HED is required to perform clinical surveillance, instigate supportive and preventative treatment, and manage ocular complications.

Natural Reconstruction: A Comprehensive Standardized Operating Procedure for Restoring Eyebrow Loss Due to Scarring.

Background:Scarring that results in eyebrow loss is a cosmetic problem that can result in severe psychological distress. Although hair transplantation is increasingly used for eyebrow restoration, graft loss may occur, preventing achievement of desired results. Single-hair follicle transplantation, however, may be effective. The authors describe outcomes of a standardized method of eyebrow reconstruction, involving single-hair follicle transplantation combined with follicular unit extraction, in patients with absent eyebrows because of scarring.Methods:This study was approved by the institutional ethics committee of Nanfang Hospital and all patients provided written informed consent before surgery. The medical records of patients who underwent eyebrow reconstruction from 2012 to 2019 for eyebrow loss caused by scar formation were reviewed retrospectively. Outcomes evaluated included satisfaction, graft survival rate, and long-term complications. A nine-step standardized operating procedure was established for eyebrow reconstruction in patients with eyebrow absence attributable to scarring.Results:During the study period, 167 patients (205 eyebrows) underwent eyebrow reconstruction. Following the first stage of reconstruction, 95 percent of patients were highly satisfied with the density and natural appearance of their eyebrows. The average graft survival rate was 85 percent (range, 70 to 90 percent), significantly higher than the 75 percent survival rate previously reported. Fewer than 5 percent of patients underwent the second stage of reconstruction, with these patients expressing satisfaction with their outcomes. No obvious complications were observed.Conclusion:This standardized method may optimize outcomes in patients with eyebrow absence attributable to scarring.CLINICAL QUESTION/LEVEL OF EVIDENCE:Therapeutic, IV.

Eyebrow Reconstruction With Temporal Hairline Relay Flap.

Eyebrow is one of the most important features of the face; the absence of eyebrows will cause a heavy psychological burden to patients. Existing brow reconstruction techniques are not perfect for every case of eyebrow defect. In this study, a patient who suffered from eyebrows loss after radiotherapy for hemangioma underwent eyebrow reconstruction with the relay transfer of a temporal hairline flap. The entire procedure was performed in the outpatient operating room. The temporal hairline flap was transferred to the eyebrow region in a relay and survived well without necrosis. In the 2-month follow-up, the shape and density of the reconstructed eyebrows were satisfactory. The operation showed this technique was innovative, economic, and recommended as a suitable choice for eyebrow reconstruction, especially in those patients with poor hair transplantation recipient area.

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.

Conradi–Hunermann syndrome: A rare case of chondrodysplasia punctata

Conradi–Hunermann syndrome is a common form of chondrodysplasia punctata, inherited as X-linked dominant disorder of cholesterol metabolism due to mutation of emopamil-binding protein gene resulting in a spectrum of skeletal, cutaneous, and ocular abnormalities. One-day-old premature, cesarean-delivered female neonate admitted with xerotic, featherlike yellow-to-white hyperkeratotic scale all over the body with craniofacial defect, coarse hair, patches of cicatricial alopecia, and absent eyebrows. Baby had rhizomelic shortening of proximal limb, clinodactyly, club foot, talipes equinovarus, and bilateral congenital cataract. Radiological skeletal survey revealed punctate stippled calcification involving left femoral head epiphysis, bilateral tarsal bones, vertebral bodies of multiple thoracolumbar vertebrae, and sternum. Serum level of 8-dehydrocholesterol was elevated. Diagnosis of rare disease can be made on clinical suspicion and radiological survey in resource-limited setting.

CLINICAL PRESENTATION OF AN EXTENDED CONSANGUINEOUS FAMILY INHERITING WOOLLY HAIR HYPOTRICHOSIS

Hypotrichosis is a hair-loss condition that is characterized by sparse hair on scalp, reduced to absent eyebrows and eyelashes. This report is presented of a D.I.Khan, Pakistan based family with multiple patients showing typical phenotype of Woolly Hair Hypotrichosis. All patients in the current family had fragile, thin, brown coloured wooly hair on the head scalp. They had sparse eyebrows but revealed normal eyelashes. Apart from hair phenotype, patients did not exhibit any abnormal features of skin and nail. Herein the shown family tree, each square and circle represent male and female person, respectively. Blacked filled symbols of male and female represent patients, while unfilled square and circle depict normal individuals. Double line, across the square and circle, shows the consanguineous marriage. Roman numbers designate generation ID, while Arabic numbers within the generation indicate” individual ID. Pedigree analysis indicate that parents of all patients have first degree consanguinity, and segregation disease in autosomal recessive fashion.

Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation-positive patients.

Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.

Novel pathogenic RECQL4 variants in Chinese patients with Rothmund-Thomson syndrome

BackgroundRothmund-Thomson syndrome (RTS) is a rare autosomal recessive disorder mainly characterized by cutaneous poikiloderma, sparse hair, short stature and skeletal defects. Deleterious mutations in the RecQ-like DNA helicase type 4 (RECQL4) gene have been detected in approximately two-thirds of RTS cases. MethodsThree Chinese patients from two unrelated families were enrolled for clinical evaluation. Targeted next-generation sequencing (NGS) using a custom panel consisting of 705 short-stature-related genes was performed for the probands. Variants detected by NGS were confirmed by Sanger sequencing and examined in family members. ResultsThe probands presented with characteristic features of severe growth delay, poikiloderma mostly on the face, buttocks and extremities, sparse or absent hair, eyelashes, and eyebrows, forearm reduction defects, small hands with hypoplasia of the middle phalanx (little finger) in one of the probands, epicanthus, hypertelorism, and dental abnormalities. In addition, novel auricle features and other rare facial features, including narrow palpebral fissure, depressed nasal bridge, and small chin were exhibited. Four novel RECQL4 variants were identified, including three pathogenic frameshift variants, c.1724_1725delAC, p.His575fs*7; c.2421dupT, p.Asp808*; c.1770_1807del, p.Pro591fs*2, and one likely pathogenic missense variant, c.691G>A, p.Gly231Ser. ConclusionOur study expands the mutational spectrum of RECQL4 gene and reveals novel phenotypes observed in Chinese RTS patients.

A recurrent missense mutation in the LPAR6 gene underlies hereditary hypotrichosis

Hypotrichosis is a heritable condition described by sparse hairs, sparse to absent eyebrows, eyelashes, axillary, and body hair, but with normal teeth and nails. Genotyping was carried out of family from fourth generation from district Sibi, Balochistan, having two affected males and one female. Genotyping was done targeting LPAR6-linked microsatellite markers present on chromosome 13q14.11-q21.32. The exon located on LPAR6 gene, were amplified of both affected and normal individuals of the family revealing linkage at locus on chromosome 13. Sequencing result of the LPAR6, shown a recurrent missense mutation c.436G>A, p. G146R) in a family. A recurrent missense mutation revealed in the current investigation encompass the evidence of LPAR6 gene hereditary hypotrichosis. Keywords: Hereditary hypotrichosis; LPAR6 gene; Missense mutation http://dx.doi.org/10.19045/bspab.2017.60072

In silico analysis of missense mutations in LPAR6 reveals abnormal phospholipid signaling pathway leading to hypotrichosis.

Autosomal recessive hypotrichosis is a rare genetic irreversible hair loss disorder characterized by sparse scalp hair, sparse to absent eyebrows and eyelashes, and sparse axillary and body hair. The study, presented here, established genetic linkage in four families showing similar phenotypes to lysophosphatidic acid receptor 6 (LPAR6) gene on chromosome 13q14.11-q21.32. Subsequently, sequence analysis of the gene revealed two previously reported missense mutations including p.D63V in affected members of one and p.I188F in three other families. Molecular modeling and docking analysis was performed to investigate binding of a ligand oleoyl-L-alpha-lysophosphatidic acid (LPA) to modeled protein structures of normal and mutated (D63V, G146R, I188F, N248Y, S3T, L277P) LPAR6 receptors. The mutant receptors showed a complete shift in orientation of LPA at the binding site. In addition, hydropathy analysis revealed a significant change in the membrane spanning topology of LPAR6 helical segments. The present study further substantiated involvement of LPAR6-LPA signaling in the pathogenesis of hypotrichosis/woolly hair and provided additional insight into the molecular mechanism of hair development.

Mutations in the lipase‐H gene causing autosomal recessive hypotrichosis and woolly hair

Hypotrichosis is characterised by sparse scalp hair, sparse to absent eyebrows and eyelashes, or absence of hair from other parts of the body. In few cases, the condition is associated with tightly curled woolly scalp hair. The present study searched for disease-causing sequence variants in the genes in four Pakistani lineal consanguineous families exhibiting features of hypotrichosis or woolly hair. A haplotype analysis established links in all four families to the LIPH gene located on chromosome 3q27.2. Subsequently, sequencing LIPH identified a novel non-sense mutation (c.328C>T; p.Arg110*) in one and a previously reported 2-bp deletion mutation (c.659_660delTA, p.Ile220ArgfsX29) in three other families.

Ectodermal Dysplasia - A Family Study

Ectodermal dysplasias (ED) are group of genetically heterogenous conditions that are characterized by abnormal development of ectodermal structures. The most affected structures are teeth, skin and its derivatives (hair, sweat glands) along with other ectodermal structures. The purpose of this work was to present the family with four boys affected with ED. We described the clinical report of male infant (affected twin) aged two months and his older brothers with absence of eyebrows and eyelashes, saddle nose, dry flaky skin, rare thin blond hair, and large number of dental anomalies with pathohistological-skin positive analysis for ectodermal dysplasia. Only a few abnormally formed teeth erupted (microdontia and conical teeth) and at the later then average age. Radiographic examination confirmed previous clinical findings and determined taurodontism of the molar teeth. They also presented pseudoprognathism of the mandible due to micrognathism of the maxilla. Based on the positive family history (two older brothers), clinical picture and pathohistological findings of the skin we concluded that the child (and his twin brother) were also affected. EDA gene missense mutation, Ala349Thr (GCA --> ACA), was responsible for the condition of observed family. Hair hypotriyhosis, brittle, scanty hair, absent or scanty eyelashes and eyebrows, blonde, fine scalp hair, as minor clinical signs at grandmother and only scanty eyelashes at mother were observed. Mutation analysis in families with X-linked ED help in genetic counseling, prenatal diagnosis, and confirmation of carrier status.

Remember the periroot sheet in orthodontic treatment of ectodermal dysplasia patients

Introduction: Root resorption has various etiologies. Recent studies have demonstrated a periroot sheet covering the root. The outermost layer of this sheet is the Malassez' epithelial layer. Tooth malformations are seen in ectodermal dysplasia and it is believed that the ectodermal layer in the periroot sheet differs in cases of ectodermal dysplasia. Case reports: Three cases of unexpected severe root resorption are demonstrated. Two cases were diagnosed with ectodermal dysplasia and the third appeared with thin, curly hair and absence of eyebrows but no ectodermal diagnosis. In the ectodermal cases, there were severe orthodontically provoked resorptions on the teeth that appeared to be permanent but were possibly primary. In the third case, there was heavy resorption on permanent teeth due to orthodontic treatment. Discussion: The orthodontist should be aware that aggressive resorption can occur in cases not diagnosed with ectodermal dysplasia but with signs of ectodermal deviations, and that tooth morphology, hair, and skin are important to observe before proceeding with treatment.