Sparse Scalp Hair Research Articles

Neonatal progeroid syndrome (Weidman Rautenstrauch syndrome): A case report from Jammu &Kashmir, India.

A female one month old with features supporting a diagnosis of neonatal progeroid syndrome(WRS) presented to our neonatology section of GB pant children hospital Srinagar .she had prenatal and post natal growth failure, generalized lipotrophy, triangular face, psedohydrocephalous, sparse scalp hair and eye brows, prominent scalp veins and greatly widened anterior fontenella.

A novel deletion mutation in theDSG4gene underlies autosomal recessive hypotrichosis with variable phenotype in two unrelated consanguineous families

Autosomal recessive hypotrichosis is a rare human hereditary disorder presenting as sparse scalp hair or as woolly hair occurring on various parts of the body. Various forms of isolated hypotrichosis have been reported to date. Mutations in at least 11 genes have been reported to cause hypotrichosis. To investigate the clinical and genetic basis of autosomal recessive hypotrichosis in two unrelated consanguineous families. Genotyping by highly polymorphic microsatellite markers established linkage in both families to the DSG4 gene on chromosome 18q21. PCR amplification of exons and intron-exon borders of the DSG4 gene was performed, and the products sequenced to search for disease-causing sequence variants. Clinical investigation revealed typical hypotrichosis in the affected members of one family, while other affected members showed presence of monilethrix-like scalp hair. Sequence analysis of DSG4 revealed a novel deletion mutation (c.85-1_191del) in the affected subjects of both families. This study further extends the body of evidence that mutations in the DSG4 gene result in both hypotrichosis and monilethrix-like scalp hair.

Clinical features, diagnostic criteria, and management of Coffin-Siris syndrome.

Coffin-Siris syndrome (OMIM#135900) is a multiple congenital anomaly syndrome classically characterized by hypo- or aplasia of the fifth digit nails or phalanges, as well as coarse facial features, sparse scalp hair, and moderate to severe cognitive and/or developmental delay. The recent identification of molecular etiologies has served to effectively characterize a large set of patients who have been described with Coffin-Siris between the time of its initial description and the present. However, despite recent advances, a number of patients who traditionally fit the diagnosis have yet to have identified causes. This could be due to patients who lie outside the defined phenotype, or alternatively, to additional as yet unidentified genes which may play roles. Here we outline the range of clinical features described in the broader diagnostic category, review the continuing phenotypic challenges and note those subsets of patients for whom molecular causes have yet to be clarified. Finally, we discuss recommendations for clinical management of these individuals.

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.

A syndrome of facial dysmorphism, cubital pterygium, short distal phalanges, swan neck deformity of fingers, and scoliosis

We report on an adolescent girl with sparse scalp hair, wide columella extending below alae nasi, webbing at elbows, broad finger tips, short distal phalanx of fingers, swan neck deformity of fingers, scoliosis, tall vertebrae, short fibulae, short fourth metatarsal bone, abnormal distal humeri, and unilateral clubfoot at birth. The combination of these features represents a novel phenotype. We sequenced the protein-coding regions of the FLNA and FLNB genes and did not observe any pathogenic sequence variation. Chromosomal microarray revealed a de novo copy number variation of uncertain clinical significance on 7p22.3.

Prevalence of cutaneous manifestations in chronic renal failure patients on regular hemodialysis: a hospital-based study

Background Chronic renal failure (CRF) presents with an array of cutaneous manifestations. Newer changes are being described since the advent of hemodialysis (HD), which prolongs life expectancy, providing time for these changes to manifest. Objective The aim of this study was to estimate the prevalence and pattern of cutaneous manifestations among patients with CRF on regular HD. Patients and methods This case-series study included 100 patients with CRF on regular HD. They were subjected to a full assessment of history, and general and dermatological examinations of the skin, hair, nails, and oral mucosa. Results All patients included in this study had at least one cutaneous manifestation attributed to CRF. The most prevalent finding was xerosis (72%), followed by pruritus (52%) and hyperpigmentation (44%), whereas purpura (2%) and bullous dermatosis (1%) were the least detected. Oral changes included xerostomia (46%), macroglossia with teeth markings (43%), fissured tongue (17%), ulcerative stomatitis (11%), and angular cheilitis (6%). The most common nail changes were absent lunula (61%), half and half nail (41%), and koilonychia (29%). Hair changes included sparse scalp hair (48%), sparse body hair (41%), and brittle and lusterless hair (39%). Hypertension and diabetes mellitus were the most common causes of CRF (53 and 18%, respectively). Conclusion Every CRF patient on HD had at least one cutaneous manifestation, which may appear before or after HD. The most common cutaneous manifestations were xerosis, pruritus, hyperpigmentation, xerostomia, macroglossia, absent lunula, half and half nail, sparse scalp hair, and sparse body hair.

Hereditary hypotrichosis simplex of the scalp.

Hereditary hypotrichosis simplex of the scalp is a genetic disorder, characterized by sparse or absent scalp hair without structural defects, in the absence of other ectodermal or systemic abnormalities. Structural hair defects may be presented with a genetic disorder affecting hair growth or part of a congenital syndrome or may indicate underlying metabolic disorders, or may be associated with other diseases. We describe a 26-years-old Persian girl suffering from hypotrichosis simplex of the scalp with trichorrhexis nodosa who had no ectodermal defects and systemic disease.

A transient myelodysplastic/myeloproliferative neoplasm in a patient with cardio‐facio‐cutaneous syndrome and a germline BRAF mutation

A male infant, born at 32 weeks gestation by cesarean because of hydrops fetalis, presented with multiple anomalies, such as sparse and curly scalp hair, absent eyebrows, frontal bossing, an atrial septal defect, pulmonary artery stenosis, and whole myocardial thickening. He was clinically diagnosed with cardio-facio-cutaneous (CFC) syndrome, and was confirmed to have a germline V-raf murine sarcoma viral oncogene homologue B1 (BRAF) c.721 A>C mutation. At 1 month of age, he presented with a transient myelodysplastic/myeloproliferative neoplasm (MDS/MPN), which improved within a month without the administration of antineoplastic agents. This is the first report of CFC syndrome with MDS/MPN. The coexistence of MDS/MPN may be related to this BRAF c.721 A>C mutation.

An interstitial deletion of 8q23.3–q24.22 associated with Langer–Giedion syndrome, Cornelia de Lange syndrome and epilepsy

We present a 19-year-old male with laxity of skin and joints, sparse scalp hair, facial dysmorphism, epilepsy, multiple exostoses, scoliosis, gastroesophageal reflux, cardiovascular defects, and an 8q23.3–q24.22 deletion detected by array comparative genomic hybridization. The patient was previously misdiagnosed as having Ehlers–Danlos syndrome. However, his clinical findings are in fact correlated with trichorhinophalangeal syndrome type II/Langer–Giedion syndrome and Cornelia de Lange syndrome-4. We discuss the genotype–phenotype correlation and the consequence of haploinsufficiency of TRPS1, RAD21, EXT1 and KCNQ3 in this case.

Neuroimaging Features in Congenital Trichomegaly: The Oliver-McFarlane Syndrome

A 23-year-old woman presented to our hospital with 9 months history of progressive ataxia, visual loss since childhood due to retinitis pigmentosa and primary amenorrhea. On examination, there were also sparse scalp hair, very long and curled upwards eyelashes and short stature. Oliver-McFarlane syndrome was suspected. Brain MRI disclosed cerebellar atrophy and hyperintense signal in corticospinal tracts on FLAIR and T2-weighted images. Therefore, brain imaging must be thoroughly investigated in patients with suspected Oliver-McFarlane syndrome, in order to determinate whether cerebellar atrophy and hyperintense signal in corticospinal tracts are part of this neurological condition.

Yunis-Varón Syndrome Is Caused by Mutations in FIG4, Encoding a Phosphoinositide Phosphatase

Yunis-Varón syndrome (YVS) is an autosomal-recessive disorder with cleidocranial dysplasia, digital anomalies, and severe neurological involvement. Enlarged vacuoles are found in neurons, muscle, and cartilage. By whole-exome sequencing, we identified frameshift and missense mutations of FIG4 in affected individuals from three unrelated families. FIG4 encodes a phosphoinositide phosphatase required for regulation of PI(3,5)P(2) levels, and thus endosomal trafficking and autophagy. In a functional assay, both missense substitutions failed to correct the vacuolar phenotype of Fig4-null mouse fibroblasts. Homozygous Fig4-null mice exhibit features of YVS, including neurodegeneration and enlarged vacuoles in neurons. We demonstrate that Fig4-null mice also have small skeletons with reduced trabecular bone volume and cortical thickness and that cultured osteoblasts accumulate large vacuoles. Our findings demonstrate that homozygosity or compound heterozygosity for null mutations of FIG4 is responsible for YVS, the most severe known human phenotype caused by defective phosphoinositide metabolism. In contrast, in Charcot-Marie-Tooth disease type 4J (also caused by FIG4 mutations), one of the FIG4 alleles is hypomorphic and disease is limited to the peripheral nervous system. This genotype-phenotype correlation demonstrates that absence of FIG4 activity leads to central nervous system dysfunction and extensive skeletal anomalies. Our results describe a role for PI(3,5)P(2) signaling in skeletal development and maintenance.

Two cases of autosomal recessive woolly hair with LIPH gene mutations

Woolly hair is a hereditary disorder characterized by fine and tightly curled hair. Autosomal recessive woolly hair (ARWH) was recently determined to result from mutations in either the lipase H (LIPH) or the LPAR6 (P2RY5) gene. An 8-year-old boy (proband) and his 11-year-old brother presented with tightly coiled and sparse scalp hair. The boys did not have cardiomyopathy, palmoplantar keratoderma, or facial dysmorphism. Their parents had normal hair growth and no woolly hair. The sequence analysis of their genomic DNA revealed that the proband and his brother had a homozygous mutation of c.736T > A in the LIPH gene. On the basis of these findings, these patients were diagnosed with ARWH. To the best of our knowledge, only 20 cases of ARWH have been previously reported in Japan. However, several reports showed that one mutation was detected in the 4/200 normal and unrelated alleles in healthy Japanese control individuals, indicating the presence of ARWH in patients with extremely mild symptoms.

Trichorhinophalangeal syndrome with low expression of TRPS1 on epidermal and hair follicle epithelial cells

Trichorhinophalangeal syndrome (TRPS) is an autosomal-dominant congenital hair loss disease characterized by sparse and slow-growing scalp hair, craniofacial and skeletal abnormalities, pear-shaped nose, thin upper lip, brittle and thin toenails, and bilateral brachydactyly of the big toes. We report a case of TRPS1 exhibiting these clinical features with a novel heterozygous single nucleotide substitution in exon 3 of the TRPS1 gene. By immunohistochemical analysis of a biopsied specimen of the patient's alopecia lesion, we found for the first time that the expression level of TRPS1 was markedly reduced in the epidermis and the outer root sheath of hair follicles as compared to a normal subject. In addition, higher expression of phospho-Stat3 was found consequent to the loss of TRPS1 in the outer root sheath.

A unique combination of 17pter trisomy and 21qter monosomy in a boy with developmental delay, severe intellectual disability, growth retardation and dysmorphisms

BackgroundMicroduplication at 17p13.3 and microdeletion at 21q22 are both rare chromosomal aberrations. The presence of both genomic imbalances in one patient has not been previously reported in literature. In this study, we performed a molecular diagnostic testing with a whole genome microarray on a 3-year-old boy with developmental delay, mental retardation and multiple malformations. MethodsA routine G-banding karyotype analysis was performed using peripheral lymphocytes. Chromosome microarray analysis (CMA) was done using Affymetrix CytoScan™ HD array. Genomic imbalances were further confirmed by multiple ligation-dependent probe amplification (MLPA). ResultsThe result of karyotyping was normal but CMA detected a 9.8Mb microduplication at 17p13.3–13.1 (chr17: 1–9,875,545) and a 2.8Mb microdeletion involving 21q22.3–qter (chr21: 45,239,077–48,097,372). The imbalances were due to a balanced translocation present in patient's mother. The patient was characterized with short stature, profound developmental delay, non-verbal, intellectual disability as well as craniofacial dysmorphism, subtle brain structural anomaly and sparse scalp hair. ConclusionsThis is the first patient reported with a combination of a microduplication at 17p13.3–13.1 and a microdeletion at 21q22.3–qter. Both genomic imbalances were undetected by conventional karyotyping but were delineated with CMA test. Synergistic effect from the two rare genomic imbalances is likely responsible for the severe clinical phenotypes observed in this patient.

Hallermann-Streiff syndrome

Hallermann-Streiff syndrome (HSS) is a rare disorder characterized by dyscephalia, with facial and dental abnormalities. We report a 12-year-old female child who presented with abnormal facial features, dental abnormalities and sparse scalp hair.

Neonatal progeroid syndrome (Wiedemann-Rautenstrauch syndrome) in an Egyptian child with premature loss of teeth, and café au lait skin patches

A female, 26months old with features supporting the diagnosis of neonatal progeroid syndrome was presented. She had prenatal and postnatal growth failure, generalized lipoatrophy except for fat pads in the suprabuttock areas, triangular face, pseudohydrocephalous, sparse scalp hair and eyebrows, prominent scalp veins, greatly widened anterior fontanels, and moderate mental retardation. The patient had also some features not reported previously as premature loss of milk teeth, large mouth, atrophic gums, protruded lower jaw, and café aulait skin patches on lower limbs. Nail dystrophy was also detected. She had local depression of the left parietal bone on CT brain, white matter demyelination in MRI brain, and high level of cholesterol.

A recessive form of Marshall syndrome is caused by a mutation in the COL11A1 gene

Recently, Tompson et al 1 described the use of autozygosity mapping and expression studies to identify compound heterozygous mutations (c.2386G>C/c.3943G>T; c.1786dupG/c.3124G>A) in the COL11A1 gene in two unrelated patients as...

Prevalent founder mutation c.736T>A of LIPH in autosomal recessive woolly hair of Japanese leads to variable severity of hypotrichosis in adulthood

Mutations in LIPH are a cause of autosomal recessive woolly hair (ARWH). Homozygous c.736T>A (p.Cys246Ser), and compound heterozygous c.736T>A and c.742C>A (p.His248Asn) have been reported in 5 and 7 Japanese children with ARWH respectively. The severity of hypotrichosis is known to be able to change in the clinical course, and the mutation patterns of LIPH do not always correlate with the severity of hypotrichosis in ARWH caused by other mutation sites of LIPH. However, all 12 Japanese children previously reported to have ARWH have shown similar severity of hypotrichosis. In this study, we investigated the clinical features and molecular basis of ARWH in patients including three adults (three adults and two children) from five non-related Japanese families. Five families of Japanese origin that presented with woolly hair were studied. The phenotype was confirmed by clinical examination. Direct automated DNA sequencing of the LIPH gene was performed to identify the mutations in our probands. All patients had had woolly hair since birth. Homozygous c.736T>A mutations were found in four patients, including three adult cases, and compound heterozygous c.736T>A and c.742C>A mutations were found in one child patient. The two adults and two children had only sparse scalp hair, although one adult woman had mild hypotrichosis with long hairs. Some patients with homozygous c.736T>A can have a mild hypotrichosis phenotype with long hairs in adulthood.

Severe diffuse non‐scarring hair loss in systemic lupus erythematosus – clinical and histopathological analysis of four cases

Although diffuse non-scarring hair loss been found common in systemic lupus erythematosus (SLE), study that conduted on the severe type has been scarce. This study aims to explore the dermoscopic and pathological features of severe diffuse hair loss in SLE. Data including clinico-laboratory, dermoscopic and histopathological findings of four patients with SLE with severe diffuse hair loss were analysed retrospectively. All four patients were women aged 41, 39, 14 and 48 with complaints of hair loss involving 55%, 100%, 60% and 55% of their scalp respectively. Common clinical findings observed in the patients were sparse scalp hair with clusters of newly regrown hair. Scalp dermoscopy showed scaling, perifollicular telangiectasia, increased numbers of short vellus hairs, focal atrichia and decreased hair shaft pigmentation. Scalp tissue histopathology revealed typical changes of SLE such as epidermal atrophy with focal liquefaction, degeneration of the basement membrane zone, pigment incontinence, mild focal perivascular and perifollicular lymphocytic infiltrates and deposition of immunoglobulins at the dermal-epidermal junction. Treatment and improvement in SLE disease activity indices had a favourable impact on hair regrowth. The severe type of hair loss in patient with SLE presents a unique set of clinical, dermoscopic and histopathological features.