Pili torti may occur as an inherited, isolated phenomenon with onset in the early months of life. The hair is usually fairer than expected and is spangled, dry and brittle. Alterations of the inner root sheath likely lead to the abnormal molding and twisting of the hair shaft on its own axis. Inheritance patterns can be autosomal dominant [16], autosomal recessive [17] or sporadic [18]. A late onset of pili torti has been described with the onset in childhood or after puberty. It is an autosomal dominant condition in white patients with black unruly, coarse, stiff hair and non-progressive mental deficiency [19]. Other inherited entities may present pili torti and include Menkes syndrome, Björnstad syndrome, Crandall syndrome and ectodermal dysplasia.

Menkes kinky hair syndrome, also known as trichopoliodystrophy, is a rare X-linked recessive, progressive neurodegenerative with connective tissue manifestations. It is clinically characterized by progressive psychomotor impairment, treatment-refractory seizures and hair shaft abnormalities [20], most commonly PT, but other defects, such as trichorrhexis nodosa (TN), have been described. The condition is related to a mutation in a copper-transporting gene located on chromosome Xq13.3 resulting in a disorder caused by deficiency or dysfunction of a copper-transporting ATPase, ATP7A [21]. Four types of Menkes disease can be distinguished. The two extremes forms, the severe classical form and the mildest, called occipital horn syndrome (OHS), affect >90 % of patients. Moderate and mild forms likely represent variant of MD and OHS. The infants appear normal at birth and then typically develop neurologic deterioration, lethargy and a loss of milestones in the second or third months of age. Skin and hair hypopigmentation and bone and connective tissue alterations with soft skin and joint laxity are present. There is microcephaly and the hair shaft does not grow long and is easily broken. Light microscopy is an important clue for the early suspicion of Menkes syndrome. Flattened hair is twisted 180° along its axis intermingled with normal hair (Fig. 14.2). The diagnosis can be confirmed by a low plasma level of copper and ceruloplasmin. If untreated, most patients die within the first year of life. Longer-term survivors are reported as a result of early treatment with parenteral administration of copper in the neonatal period. It may prevent neurological deterioration but does not improve the non-neurological features such as hair or connective tissues laxity [22].

In 1965, Björnstad described eight patients with pili torti and hearing loss [23]. The combination of these two findings was later coined Björnstad’s syndrome. Patients develop hair loss in the first 2 years of life, while the hearing deficit may become evident in the first 3–4 years of age. Only 39 cases of Björnstad syndrome have been reported in the English literature and only two cases have been reported in Japan [24].

Both autosomal and recessive inheritance patterns have been described and mapped to the gene locus 2q34–q36 [25]. Al-Owain et al. described a novel phenotype in a series of nine Saudi Arabian patients from four consanguineous families three of which were related. They identified a causative mutation in the BCS1L gene [26].

Crandall syndrome is similar to Björnstad syndrome but presents with hypogonadism [27]. Most cases are autosomal recessive.

Mental retardation is rarely associated in both syndromes.

TN may occur alone but has been reported in certain genodermatoses and metabolic disorders.

In congenital TN, inherited as an autosomal dominant trait, the hair is usually normal at birth but is replaced within a few months with abnormal, fragile hair. The condition tends to improve with age.

In two main metabolic inborn errors of the urea cycle, argininosuccinic aciduria and citrullinemia, TN can occur. TN occurs in approximately 50 % of cases of the neonatal form of argininosuccinic aciduria while in citrullinemia may present TN, atrophic hair bulbs, and/or pili torti. Clinically, manifestations are similar in both conditions; symptoms include lethargy, seizures, respiratory distress and development delay. Hair is usually normal at birth, with later development of dry, dull hair and TN. The light microscopic appearance of TN is a fracture associated with swelling of cortical cells and splaying them out from the main body of the hair shaft resembling the end of a brush (Fig. 14.3). The condition reverts to normal with dietary treatment of the metabolic condition, but it recurs quickly if the diet is abandoned [28].

Trichothiodystrophy (TTD) is a heterogeneous rare group of autosomal recessive disorders of DNA repair unified by the presence of sulfur-deficient brittle hair. It is caused by a mutation of a regulatory gene involved in the transcription of DNA. There is a wide variety of phenotypes, from brittle hair only to severe intellectual impairment and developmental delay (Fig. 14.5).

Eight subgroups have been categorized by Itin et al. [29] and include BIDS (brittle hair, intellectual impairment, decreased fertility, and short stature), IBIDS (BIDS + ichthyosis), PIBIDS (BIDS + photosensitivity), SIBIDS (otosclerosis + IBIDS), ONMR (onychotrichodysplasia, chronic neutropenia, and mental retardation), and Sabinas, Pollitt, and Marinesco–Sjögren syndromes [30]. Individuals with TTD may present with a collodion baby phenotype and intrauterine growth retardation can occur.

In TTD, 95 % of photosensitivity patients have abnormalities in nucleotide excision repair (NER) and can be assigned to the xeroderma pigmentosum (XP) complement group D (XPD) [29]. Non-photosensitivity TTD patients represent a genetically heterogeneous disorder. Mutations in chromosome 7p14 have been identified in two types of patients with Amish brittle-hair syndrome and non-photosensitivity TTD with mental retardation and/or decreased fertility [31].

The clinical appearance is a short, brittle, disordered sparse hair. This may be absent at birth and is not fully developed until 3 months of age [32]. On light microscopy, the hair has an irregular outline and a flattened shaft in which twists occur like a folded ribbon. Two types of fractures are seen—trichoschisis and an atypical trichorrhexis nodosa (less splaying out of the cortical cells). Under polarized light the typical “tiger tail” pattern confirms the diagnosis. The low cystine (sulfur) content of hair is postulated to account for cuticular and cortical weakness, provoking the fracture. A study reveals an inverse correlation between sulfur content and percent of hairs with shaft abnormalities (trichoschisis, trichorrhexis nodosa, or ribbon/twist), but there was no association between clinical disease severity and percent of abnormal hairs [33].

Diagnosis. Is made by visualization of the “tiger tail” banding seen in all hairs with polarizing microscopy providing a reliable diagnostic test. Scanning electron microscopy shows a flattened shaft with irregular ridging and disordered reduced, or absent cuticle scan pattern.

Netherton syndrome (NS) is a severe autosomal recessive skin disorder characterized by congenital ichthyosiform erythroderma, TI, and atopic manifestations with an elevated IgE level [34]. Recently, pathogenic mutations were identified in serine protease inhibitor Kazal-type 5 (SPINK5) [35], the gene that encodes lympho-epithelial Kazal-type related inhibitor (LEKTI), a type of serine protease inhibitor involved in the regulation of skin barrier formation and immunity. The major neonatal complication is the hypernatremic dehydration and staph skin infections complicated by neurologic signs.

Although the severity varies considerably, the clinical and microscopic findings are present from birth with a large variability in phenotypic expression. Most patients present a congenital generalized exfoliative erythroderma which can last up to 2 years followed by an ichthyosiform eruption with polycyclic erythematous plaques with fine double-edged scaling, named ichthyosis linearis circumflexa (Fig. 14.6).