Syndromes Associated with Hair Disorders

ABSTRACT

Syndromes, defined as clusters of consistent symptoms, are vital in understanding diseases and disorders. The interplay between hair and clinical syndromes is examined in brief here, emphasizing the need for a unified data resource to aid clinicians and postgraduate students. The syndromes are categorized into hypertrichosis, characterized by excessive hair growth, and hypotrichosis, defined by a lack of hair. For hypertrichosis, various syndromes such as Ambras, Cantú, and Rubinstein-Taybi syndrome are elucidated, highlighting their distinct clinical features and genetic underpinnings. Hypotrichosis syndromes include Bjornstad’s, Netherton and Rothmund-Thomson syndromes. By categorizing and elucidating the array of hair-related syndromes, this comprehensive review aims to enhance clinical understanding and improve patient care in this domain.

INTRODUCTION

Syndrome is a group of symptoms which consistently occur together. The word “Syndrome” derives from the Greek meaning “concurrence.”. When a syndrome is paired with a definite cause, this becomes a disease. In some instances, a syndrome is so closely linked with a pathogenesis or cause that the words syndrome, disease, and disorder end up being used interchangeably for them.

Hair, an appendage of the skin has more often than not, amassed more popularity for its cosmetic appeal than it is medical relevance but it still continues to form an integral part of many clinical syndromes. There is a lack of collective data as a one-stop solution for all syndromes involving hair. Herein, we have attempted to group together in alphabetical order all the syndromes involving hair, hoping it serves as a useful tool for clinicians and postgraduate students worldwide. Syndromes associated with hair disorders can be grouped as hypertrichosis or hypotrichosis.

Hypertrichosis is defined as excessive hair growth anywhere on the body in either males or females. It is important to distinguish hypertrichosis from hirsutism, which is a term reserved for females who grow an excessive number of terminal hairs in androgen-dependent sites. Syndromes associated with hypertrichosis are tabulated in Table 1.

Table 1.

Syndrome associated with hypertrichosis

Syndromes associated with hypertrichosis

AS

Barber-Say syndrome

CAHMR syndrome

Cantu syndrome

Coffin siris syndrome

Cornelia de lange syndrome

Districhiasis-lymphedema syndrome

Fetal alcohol syndrome

Fetal hydantoin syndrome

Gorlin Chaudry Moss syndrome

H syndrome

HAIR-AN syndrome

Hurler’s syndrome

Hypertrichosis cubiti: Hairy elbow syndrome

Lawrence-Seip Syndrome (acquired generalized lipodystrophy)

Oliver-McFarlane’s syndrome (Trichomegaly syndrome)

PCOS

POEMS syndrome

Rubinstein Taybi syndrome

Schinzel-Gieldon midface retraction syndrome

Stiff skin syndrome

Waardenburg’s syndrome

Winchester syndrome/MONA syndrome

Zimmerman Laband syndrome

CAHMR - Cataract, hypertrichosis, and mental retardation; HAIR-AN - Hyperandrogenism insulin resistance acanthosis nigricans; PCOS - Polycystic ovary syndrome; POEMS - Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin abnormalities; MONA - Multicentric osteolysis, nodulosis, and arthropathy

1. Ambras syndrome (AS) (hypertrichosis universalis congenita, Ambras type; HTC1)[1]

   • AS is a rare and special form of congenital hypertrichosis, associated with dysmorphic facial features and a familial pattern of inheritance

   • This condition affects both the sexes without any racial and geographical distribution

   • Clinically, it manifests mucocutaneous as long, fine, vellus hair covering the entire body, sparing the palms, soles, mucous membranes, and dorsal terminal phalanges and associated with dysmorphic facial features such as triangular, coarse face, broad palpebral fissures, bushy eyebrows, hypertelorism, prominent bulbous nose, round nasal tip, large interalar distance, anteverted nares, and flat sulcus mentolabialis.

2. Barber–Say syndrome[2]

   • It is a rare congenital disorder characterized by hypertrichosis, redundant skin, hypoplastic or absent nipples, and dysmorphic facial features including macrostomia, bulbous nose, ocular telecanthus, eyelid ectropion, and abnormal ears

   • TWIST2 mutation is reported in various case reports

   • Genetic testing forms the basis of further prevention

   • Dermis and/or subcutaneous septa may help to confirm this diagnosis.

3. CAHMR (Cataract-hypertrichosis-intellectual disability syndrome) syndrome[3]

   • It is congenital acquired hypertrichosis, associated with congenital lamellar cataracts and mental retardation

   • Additional features consist of macrodontia and pectus excavatum

   • In a family, an autosomal recessive inheritance was suggested.

4. Cantú syndrome (hypertrichotic osteochondrodysplasia)[4]

   • Cantú syndrome is characterized by congenital hypertrichosis; distinctive coarse facial features enlarged heart with enhanced systolic function or pericardial effusion and in many, a large patent ductus arteriosus requiring repair; and skeletal abnormalities

   • The diagnosis of Cantú syndrome is established in a proband with suggestive clinical findings and a heterozygous pathogenic variant in ABCC9 or KCNJ8 identified by molecular genetic testing

   • Depilatories or laser hair removal for hypertrichosis can be tried.

5. Coffin–Siris syndrome (CSS)[5]

   • Inherited in an autosomal dominant manner

   • CSS is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degrees, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair

   • The diagnosis of CSS is established in a proband with suggestive findings by identification of a heterozygous pathogenic variant.

6. Cornelia de Lange Syndrome also known as Brachmann-de Lange syndrome[6]

   • It is inherited as an autosomal dominant and X-linked recessive gene, mainly due to mutation in SMC1A and NIPBL gene

   • Patients have a low birth weight and are short of stature, demonstrating dwarfism. Respiratory difficulties, frequently a cognitive deficit, and a characteristic face-small nose, low ear implantation, prominent philtrum, commissures of the mouth inclined downwards, widely spaced teeth, confluent eyebrows (synophrys) are seen

   • Hypertrichosis which includes long, curly eyelashes, and a low hair implantation line is observed on both the forehead and the neck.

7. Districhiasis–Lymphedema syndrome[7]

   • It is an autosomal dominant disorder with a mutation in FOXC2 gene

   • It is a triad of primary lymphedema, distichiasis, and ocular manifestations. Patients will have extra eyelash over inferior or superior eyelids ranging from the full set of extra eyelashes to single hair

   • Ocular manifestations include ptosis, corneal irritation, recurrent conjunctivitis, and photophobia

   • Other associated features include congenital heart disease, renal anomalies, varicose veins, web neck, and cleft palate.

8. Fetal Alcohol syndrome[8]

   • Develops in a high proportion of infants born to alcoholic mothers

   • The infant is small and microcephalic with retarded milestones, heart, and joint defects

   • Hypertrichosis and capillary angiomatosis accompany distinctive facies (short palpebral fissures, prominent nose, and maxillary hypoplasia).

9. Fetal hydantoin syndrome[9]

   • It results from maternal consumption of phenytoin

   • Fetus presents with hypertrichosis, low posterior hairline, short webbed neck, depressed nasal bridge, ocular hypertelorism, and psychomotor retardation.

10. Gorlin–Chaudry–Moss syndrome (GCMS)[10]

    • GCMS is a rare disorder consisting of craniofacial dysostosis, hypertrichosis, underdeveloped genitalia, and ocular and dental anomalies

    • Caused by recurrent mutations affecting the 217^th amino acid in SLC25A24

    • Have a similar genetic basis as Fontane syndrome.

11. H syndrome[11]

    • H syndrome is a systemic autosomal recessive inherited histiocytosis, with characteristic cutaneous findings accompanying systemic manifestations without any standard treatment for better controlling or progression prevention of the diseases

    • Presents with hyperpigmentation and hypertrichosis, hepatosplenomegaly, heart anomalies, hearing loss, hypogonadism, low height, and occasionally, hyperglycemia[12]

    • Hypertrichosis can be almost permanently removed by laser.

12. Hyperandrogenism, insulin resistance, and acanthosis nigricans (HAIR-AN) syndrome[13]

    • HAIR-AN – A syndrome of HAIR-AN – is a specific and rare subphenotype of the polycystic ovary syndrome (PCOS) characterized by the presence of severe IR

    • Hirsutism is a presenting feature where laser therapy can be helpful

    • Laser can be helpful in hirsutism

    • Combined hormonal contraceptives that contain both ethinyl estradiol (EE) and a progestin or antiandrogen such as cytoproterone, and metformin, an insulin-sensitizing agent, are considered first-line therapy to reduce IR and regulate the menstrual cycle.

13. Hurler’s syndrome[14]

    • Hurler syndrome is a rare autosomal recessive lysosomal storage disorder

    • Affected individuals demonstrate typical coarse facial features including a flat nasal bridge and excessive hair growth

    • Usually manifests as cognitive developmental delay, corneal clouding, cardiac disease, and characteristics of musculoskeletal manifestations.

14. Hypertrichosis cubiti: (Hairy elbow syndrome)[15]

    • Described by Beighton in 1970, a congenital malformation characterized by the presence of hypertrichosis symmetrically at birth, or which develops during infancy around the elbows, extending from midhumerus to midforearm

    • The mode of inheritance remains unclear an autosomal recessive, or autosomal dominant form with variable penetrance and expression, or a spontaneous mutation

    • Initially, the hairs tend to be fine, but later on, at approximately aged 5 years, these become long and woolly, tending to disappear as of adolescence

    • It has been associated with short stature, brachydactyly, short nails, short nose, antimongoloid slant of the eyes, ptosis and an asymmetrical face, diabetes mellitus, limb abnormalities, and developmental disorders.

15. Lawrence–Seip syndrome (acquired generalised lipodystrophy)[16]

    • It is characterized by atrophy of subcutaneous adipose tissue, IR, hyperinsulinemia, and diabetes mellites

    • There is complete loss of the subcutaneous adipose tissue, which is always evident before the age of 2 years, hepatomegaly, splenomegaly, hyperlipemia, xanthomas, and excessive bone growth and clitoris growth, with genital precocity

    • Hypertrichosis is visible from birth, although it becomes more evident with age, especially on the face, where the hairs on the head merge into those of the eyebrows and cheeks. There is also hypertrichosis on the neck, arms, and legs

16. Oliver-McFarlane syndrome (Trichomegaly syndrome).[17]

    • It is a very rare condition with genetic analysis placed within the group of PNPLA6-related disorders

    • Only 33 clinically documented cases have been found till 2021, all sporadic

    • It is characterized by physical and mental retardation, pigmentary degeneration of the retina and the eyelashes, and very long eyebrows which need to be cut periodically, contrasting with an especially notable hypertrichosis on the occipital area.

17. Polycystic ovarian syndrome[18]

    • Polycystic ovary syndrome is the most common endocrine disorder affecting women of reproductive age, involving pathways that produce metabolic, reproductive, cardiovascular, and dermatologic effects

    • Any two of the following is required for the diagnosis: oligo or anovulation, hyperandrogenism (clinical or biochemical), and polycystic ovarian morphology on transvaginal ultrasonography

    • Hirsutism and acanthosis nigricans are the most reliable clinical markers of PCOS.

18. POEMS syndrome also known as Crow–Fukase syndrome also known as Takatsuki syndrome:[19]

    • A rare entity characterized by the association of peripheral neuropathy of the sensory-motor polyneuropathy type, organomegaly, one or more endocrinopathies, and presence of monoclonal gammopathy

    • Hyperpigmentation is present in 90% of cases; edema in 80% of cases; and hypertrichosis in 71% of cases, especially on the lower limbs

    • Patient should have at least 3 or more of the 5 features

    • There is the elevation of interleukin-1 (IL-1) beta, IL-6, tumor necrosis factor-alpha (TNF-α), and vascular endothelial growth factor.

19. Rubinstein-Taybi syndrome

    • Mental deficiency, dwarfism, the presence of broad and large big toes, and a “bird face” with an antimongoloid palpebral fissure, high-arched palate, pointed nose, irregular teeth, and low implantation of large ears

    • In 64% of cases, hypertrichosis of the trunk, limbs, and face, with a low frontal hair implantation line.

20. Schinzel–Giedion midface retraction syndrome[20]

    • It is inherited in autosomal recessive inheritance

    • The midface retraction which is pathognomonic consists of shallow orbits and midface hypoplasia with resulting prominence of the forehead, large fontanelles, and widely patent cranial sutures, particularly the metopic suture

    • Babies with Schinzel–Giedion syndrome often have excessive hairiness (hypertrichosis) that usually disappears in infancy.

21. Stiff Skin syndrome[21]

    • Stiff skin syndrome is a scleroderma-like disorder that presents in infancy or early childhood with rock-hard skin, limited joint mobility, and mild hypertrichosis in the absence of visceral or muscle involvement, immunologic abnormalities, or vascular hyperreactivity

    • Supportive histopathologic findings consisting of either fascial sclerosis or increased fibroblast cellularity with sclerotic collagen bundles in the deep reticular.

22. Waardenburg’s syndrome[22]

    • Presents with congenital perceptive deafness, broad nasal root, confluent eyebrows, lateral displacement of the medial canthi, heterochromia irides, premature canities, white forelock, and hypopigmented macules

    • Sensory neural hearing loss (SNHL), abnormal pigmentation of the iris, and diagnosed first-degree relative form the major diagnostic criteria for the diseases.

23. Winchester syndrome (MONA syndrome)

    • Characterized by the presence of dwarfism, joint destruction, corneal opacities, osteolysis of the carpal and the tarsal bones, osteoporosis, and a thickened and hyperpigmented skin with hypertrichosis.

24. Zimmermann–Laband syndrome[23]

    • It is an extremely rare autosomal dominant congenital disorder. It is a craniofacial malformation syndrome with predominant intraoral involvement consisting of gingival fibromatosis diffusion in early development

    • It is also characterized by hypo/aplastic nails and distal phalanges, abnormalities of soft cartilages of the nose and/or ears, hepatosplenomegaly, hyperextensibility of joints, mild hirsutism, hypertrichosis, and intellectual disability.

Hypotrichosis refers to a sparsity of hair that is present right at or soon after birth. Syndromes associated with hypotrichosis are tabulated in Table 2.

Table 2.

Syndromes associated with hypotrichosis

Syndromes associated with hypotrichosis/alopecia

Alopecia epilepsy oligophrenia syndrome of Moynahan

BDC syndrome

Bjornstad’s syndrome

Carvajal syndrome

Christ–Siemens–Touraine syndrome/HED

Clouston syndrome/hidrotic ectodermal dysplasia

Conradi Hunermann Haple syndrome

Crandall’s syndrome

Cushing’s syndrome

Graham Little-Piccardi-Lassueur syndrome

Hallermann Streiff Syndrome/Francois dyscephaly syndrome/Hallermann-Streiff-Francois syndrome

Loose anagen hair syndrome

Marie–Unna syndrome

Marinesco–Sjögren syndrome

Menkes’ kinky hair syndrome (trichothiodystrophy)

Naxos syndrome

Netherton syndrome

Pseudothalidomide syndrome

RHS

RTS

TRPS

Uncombable hair syndrome (syndrome spun-glass hair, pili trianguli et Canaliculi, Cheveux Incoiffables)

HED - Hypohidrotic ectodermal dysplasia; RHS - Rapp Hodgkin Syndrome; RTS - Rothmund-Thomson syndrome; BDC - Bazex-Duprol-Christol; TRPS - Tricho–rhino–phalangeal syndrome

1. Alopecia epilepsy oligophrenia syndrome of Moynahan[24]

   • A rare, genetic syndrome with an autosomal recessive trait characterized by congenital alopecia, early-onset epilepsy, intellectual disability, and speech delay

   • Large stature, delayed bone development, microcephaly with abnormal electroencephalogram, and hypogonadism have been associated.

Four types of Moynahan syndrome have been suggested [Table 3].

Table 3.

Types of Moynahan syndrome

Types	Features
Type I	Total alopecia and mental retardation, in association with microcephaly
Type II	subtotal alopecia and mental retardation with or without epilepsy
Type III	subtotal alopecia and psychomotor retardation with microcephaly and epilepsy
Type IV	Universal alopecia, intellectual disabilities, developmental delay, epilepsy

• 2. BDC syndrome[25]

  • Bazex-Duprol-Christol syndrome is inherited as an X-linked dominant syndrome and has a classical triad of congenital hypotrichosis, follicular atrophoderma, and multiple basal cell carcinomas

  • Associated features include milia formation, characteristic facial features such as a pinched nose with hypoplastic ala and prominent columella, atopic dermatitis, keratosis piliaris, hypermobility of joints, and multiple epidermal cysts

  • Hair shaft defects are pili torti and trichorrhexis nodosa.

• 3. Bjornstad’s syndrome[26]

  • It is an autosomal recessive disorder caused by a mutation in the BCS1L gene which codes for a chaperone protein

  • It is characterized by pili torti (flat and twisted hair shafts) on scalp and body hairs that lead to fragile lustreless hairs. Patients will have sensorineural hearing loss in 3 to 4 years. Cells of the inner root sheath are specifically sensitive to the accumulation of reactive oxygen species, leading to deafness and hair shaft defects

  • Associated symptoms include anhidrosis, speech difficulties, intellectual disabilities, and hypogonadism.

• 4. Carvajal syndrome[27]

  • It is a triad of woolly hairs (since birth), palmoplantar keratoderma (during infancy), and left ventricular hypertrophy (asymptomatic during the first few years but can lead to sudden cardiac death during adolescence)

  • It is due to a mutation in the gene encoding desmoplakin on chromosome 6p24

  • Other associated symptoms are clubbing of fingers, follicular keratosis over the knee and elbows, and transient purpuric blisters.

• 5. Christ–Siemens–Touraine syndrome also known as hypohidrotic ectodermal dysplasia (HED)[28]

  • Approximately one-third of cases are inherited in either an autosomal recessive or autosomal dominant pattern, of which males and females are affected equally, whereas males are disproportionately affected by the X-linked HED

  • The genes involved encode proteins utilized in the TNF-α signaling pathway

  • Hypohidrosis due to hypoplasia of sweat glands leads to fever in a child and heat intolerance throughout life, especially during exercise. Scalp hair is thin, sparse, slow-growing, and lightly pigmented, though secondary sexual hair can be normal.

• 6. Clouston Syndrome also known as hidrotic ectodermal dysplasia[29]

  • A rare autosomal dominant disorder characterized by nail thickening/shortening, palmoplantar keratoderma, and short, thin sparse hair, and is caused by different mutations in the gap junction b6 gene (GJB6), which encodes for connexin-30

  • The patient presents with pale-colored, patchy, wiry, and brittle scalp hair during infancy, with progressive hair loss typically, leading to total alopecia by puberty, has the ability to sweat, and have normal dentition. Eyebrows, axillary, and pubic hair are sparse or absent, and eyelashes are short and sparse

  • The diagnosis can be confirmed by genetic analysis.

• 7. Conradi Hunermann Haple syndrome[30]

  • It is a rare genetic disorder characterized by skeletal dysplasia, stippled epiphyses, cataracts, transient ichthyosis, and atrophic residua in a mosaic pattern, X-linked dominant disorder due to mutation in emopamil binding protein

  • It occurs almost exclusively in females. Cutaneous involvement typically starts as a severe congenital ichthyosis with adherent large scales following the lines of Blaschko on an erythrodermic background. Patchy cicatricial alopecia with coarse, lustre-less hair often emerges on the scalp and represents the most conspicuous constant cutaneous feature in many cases

  • Diagnosis is confirmed by plasma sterol and mutation analysis.

• 8. Crandall’s syndrome[31]

  • It is an autosomal recessive disorder, characterized by a triad of deafness, hypogonadism (Luteinizing hormone- LH, growth hormone- GH deficiencies), and alopecia, associated with pili torti, and therefore it resembles with Bjornstad syndrome (deafness and pili torti).

• 9. Cushing’s Syndrome[32]

  • Cushing’s syndrome is an endocrine disorder that comprises a large group of signs and symptoms resulting from chronic exposure to excess corticosteroids

  • The prominent skin findings reflect the hypercatabolic effects of hypercortisolism-purple striae and hyperpigmentation

  • In contrast, female baldness or female hair loss has been variably reported and is rarely the chief complaint of a patient presenting with Cushing’s syndrome.

• 10. Graham Little-Piccardi-Lassueur syndrome[33]

  • Piccardi in 1913, described a case of progressive scalp cicatricial alopecia, noncicatricial alopecia in the axilla and pubic area, and follicular spinous papules on the trunk and extremities, to which he gave the name cheratosi spinulosa (keratotic spinulosa). Graham Little, later in 1915 published a similar case of a 55-year-old woman, which was described as “folliculitis decalvans et atrophicans”

  • It is a type of lichen planopilaris characterized by the triad of patchy cicatricial alopecia of the scalp, noncicatricial alopecia of the axilla and groin, and a follicular spinous papule on the body, scalp, or both.

• 11. Hallermann Streiff Syndrome also known as Francois dyscephaly syndrome[34]

  • It a type of ectodermal dysplasia with a mutation in GJA1 gene

  • Rare entity first described in the medical literature in 1893, characterized by distinctive malformations of the skull and facial (craniofacial) region; sparse hair (hypotrichosis); eye abnormalities; dental defects; degenerative skin changes (dermal atrophy), particularly in the scalp and nasal regions; and proportionate short stature

  • Characteristic facial features include brachycephaly and frontal bossing, beak-shaped nose, microphthalmia, and dental anomalies

  • Cutaneous manifestations include sparse, brittle, lustreless hairs over scalp, café au lait macules, acanthosis nigricans, dermal atrophy, and koilonychia.

• 12. Loose anagen hair syndrome[35]

  • It is a sporadic/autosomal dominant disorder, mostly due to impaired keratinization of the inner hair root sheath. Mutation in genes K6HF and K6IRS is also involved in loose anagen hairs

  • It is predominantly seen in girls aged between 2 and 6 years. Parents complain that child’s hair is sparse, lustreless, and does not grow. Hairs can be easily pluckable and extracted without pain

  • Phenotypes of loose anagen syndrome are: [Table 4]

  • Hair pluck trichogram will show floppy sock appearance of anagen hairs due to ruffled cuticle

  • Histopathological examination of scalp biopsy shows cleft in IRS and ORS.

• 13. Marie–Unna syndrome[12]

  • It is an autosomal dominant disorder characterized by a distinctive pattern of hair loss

  • Mutation of the U2HR gene, located in chromosome 8p21 is responsible

  • Individuals are born with sparse or absent hairs at birth, later there is regrowth of coarse, unruly hair in childhood and progressive, nonscarring loss of hair again at or nearing puberty

  • There is a receding of hair line with increasingly sparse hair on the vertex, parietal, and occipital region resembling androgenetic alopecia. Eyebrows, eyelashes, body hair, and secondary sexual hair are sparse or absent

  • Eyebrow loss and the presence of wiry, twisted hair is important for diagnosis.

Table 4.

Phenotypes of loose anagen syndrome

Types	Features
Type A	Decreased hair density
Type B	Unruly hair
Type C	Normal-appearing hair with excessive shedding of anagen hairs

Marinesco–Sjögren syndrome[36]

• It is inherited in an autosomal recessive manner

• Clinical features include trichoschisis, nail and teeth defects, physical and mental retardation, and cerebellar ataxia. Progressive myopathy and cataracts

• Carrier testing for at-risk relatives and prenatal and preimplantation genetic testing is possible if the pathogenic variants in the family are known

14. Menkes’ kinky hair syndrome (trichopoliodystrophy)[37]

• This X-linked recessively transmitted disorder caused by mutations in ATP7A gene is located on Xq12–q13. A copper metabolism defect results in the alteration of keratinization as well as pigmentation of hair, as copper is required in the formation of melanin as well as cystine synthesis

• The hair is normal at birth but after the shedding of the first hair in infancy the new hair that grows are light-colored, twisted, and fragile with a “steel wire” appearance. Diagnosis after the first 3 months of life is relatively easy because of the characteristic hair changes and advanced systemic features.

Naxos syndrome[38]

• It is an autosomal recessive disorder occurring due to a mutation in the plakoglobin gene on chromosome 17q21, causing truncation in the C terminal of protein

• It is characterized by a triad of woolly hair, palmoplantar keratoderma, and arrhythmogenic right ventricular cardiomyopathy

• Woolly hairs are present since birth while palmoplantar keratoderma starts in infancy as the child starts to use his/her hands and feet

• Cardiac abnormalities were detected during the early adolescent period in the form of electrocardiogram abnormalities (low voltage ECG, T-wave inversion, and Epsilon wave).

15. Netherton’s syndrome[39]

• It is an autosomal recessive condition characterized by a triad of symptoms, which include congenital ichthyosis, atopic features, and hair structural abnormalities. Pathogenic mutations in SPINK5, located on 5q32, resulting in decreased expression of a large serine protease inhibitor termed LEKTI

• The syndrome often manifests soon after birth with generalized erythroderma and scaling

• Hair abnormalities, in contrast with skin changes, are seldom apparent before the first year of age. Hair microscopy can reveal the characteristic bamboo hairs or trichorrhexis invaginata, which underlie a progressive alopecia involving the eyebrows first and scalp areas later on

• Newborns are at risk for numerous and often life-threatening complications such as hypernatremic dehydration and other electrolyte imbalances, impaired thermoregulation, and systemic infections

• Cutaneous features are invariably accompanied by atopic manifestations such as allergic rhinitis, asthma, allergic reactions to food and common antigens, and elevated immunoglobulin E levels.

16. Pseudothalidomide syndrome[40]

• It is an autosomal recessive disorder due to a mutation in ESCO2 gene

• Characterized by hypomelia, hypotrichosis, and a port-wine stain-like facial capillary hemangioma

• The patient will have cleft lip-cleft palate, nose and ear abnormalities, hypertelorism, and prominent eyes with corneal clouding, microcephaly, and mental retardation

• Prenatal diagnosis is possible with chorionic villi sampling and amniocentesis.

Rapp Hodgkin syndrome[41]

• It is a type of anhidrotic ectodermal dysplasia, described by Rapp and Hodgkin in 1968, with autosomal dominant inheritance

• It is a distinct clinical entity or part of EEC syndrome (ectodactyly, ectodermal dysplasia, and cleft lip/ palate syndrome) from a mutation in TP63 (tumor protein p63) gene. EEC syndrome results

• Other dermatological features include coarse and wiry hairs, small mouth, narrow nose, oligodontia or anodontia, conical teeth, anonychia, hyponychia, narrow or dystrophic nails, lacrimal duct abnormalities, ear and ear canal abnormalities, and genitourinary abnormalities.

17. Rothmund–Thomson syndrome[42]

• It is inherited in an autosomal recessive manner

• Usually characterized by a rash that progresses to poikiloderma; sparse hair or total alopecia, sparse or absent eyelashes, and/or eyebrows; small size; skeletal and dental abnormalities; juvenile cataracts; and an increased risk for cancer, especially osteosarcoma.

18. Tricho–rhino–phalangeal syndrome (TRPS)[31]

• Is a group of two autosomal dominant genetic diseases (TRPS I and TRPS II) characterized by skeletal abnormalities, distinct facial features, and ectodermal features

• Clinical features include a large pear-shaped nose, thick and broad eyebrows, prominent ears, short stature, short digits, cone-shaped epiphyses, dystrophic nails, and fine, sparse hair

• TRPS II may be accompanied by mild-to-moderate intellectual disability

• Hairs are typically fine, sparse, slow-growing, and not very pigmented

• The pattern of hair loss is similar to that seen in male pattern baldness, with the recession of the frontotemporal hairline and thinning of hair diameter. Approximately one-third of males go nearly or completely bald within a few years after puberty, whereas women typically keep most of their hair but have a high frontal hairline. Patients may have sparse lateral eyebrows and eyelashes

• TRPS II, arise de novo and thus family history is not necessary to make a diagnosis. Sequence analysis can typically confirm the diagnosis of TRPS I, and chromosomal microarray analysis can be used to diagnose TRPS II.

19. Uncombable Hair Syndrome (Syn. Spunglass Hair, Pili Trianguli et Canaliculi, Cheveux Incoiffables)[31]

• Most reported cases are sporadic, but autosomal dominant and autosomal recessive inheritance has been described

• Mutations are located in three genes involving peptidylarginine deiminase 3, transglutaminase 3, and trichohyaline

• Most often present in infancy or early childhood. Spun-glass-appearing scalp hairs that are dry, curly, blond, and totally resist all efforts of styling. Hair is not fragile and grows normally. Hair texture and manageability improve with aging

• Associated conditions include ectodermal dysplasia, retinal dysplasia/pigmentary dystrophy, juvenile cataract, tooth enamel anomalies, oligodontia, digit abnormalities, and phalangoepiphyseal dysplasia.

CONCLUSION

Hair’s clinical importance, often overshadowed by its aesthetic allure, remains significant, contributing to various syndromes. A comprehensive grasp of hair-related syndromes is crucial for healthcare professionals. Categorizing them into hypertrichosis and hypotrichosis facilitates precise diagnosis and tailored treatments, enhancing the overall management of these conditions.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.