Localized autosomal recessive hypotrichosis is characterized by fragile hairs that break easily, leaving short, sparse scalp hairs. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, ... Localized autosomal recessive hypotrichosis is characterized by fragile hairs that break easily, leaving short, sparse scalp hairs. The disorder affects the trunk and extremities as well as the scalp, and the eyebrows and eyelashes may also be involved, whereas beard, pubic, and axillary hairs are largely spared. In addition, patients can develop hyperkeratotic follicular papules, erythema, and pruritus in affected areas. In some patients with congenital hypotrichosis, monilethrix-like hairs showing elliptical nodes have been observed (summary by Schaffer et al., 2006). - Genetic Heterogeneity of Autosomal Recessive Localized Hypotrichosis LAH2 (HYPT7; 604379) is caused by mutation in the LIPH gene (607365) on chromosome 3q27, and LAH3 (HYPT8; 278150) is caused by mutation in the LPAR6 (P2RY5) gene (609239) on chromosome 13q14.12-q14.2. See also hypotrichosis and recurrent skin vesicles (613102), which is caused by mutation in the DSC3 gene (600271).
Kljuic et al. (2003) reported 2 consanguineous Pakistani pedigrees with autosomal recessive localized hypotrichosis. Affected members displayed hypotrichosis restricted to the scalp, chest, arms, and legs. Facial hair, including eyebrows and beard, was less dense, and axillary hair, ... Kljuic et al. (2003) reported 2 consanguineous Pakistani pedigrees with autosomal recessive localized hypotrichosis. Affected members displayed hypotrichosis restricted to the scalp, chest, arms, and legs. Facial hair, including eyebrows and beard, was less dense, and axillary hair, pubic hair, and eyelashes were spared. Overall, the patients' skin was normal except for patches of scalp where small papules were visible, likely a consequence of ingrown hairs. Histologic analysis of scalp skin revealed abnormal hair follicles and shafts, which were thin and atrophic and often appeared coiled up within the skin due to their inability to penetrate the epidermis. Another defect was a marked swelling of the precortical region, resulting in the formation of a bulbous 'bleb' within the base of the hair shaft. Rafique et al. (2003) described multiple members of 3 consanguineous kindreds from different regions of Pakistan who had LAH. They had hair on the scalp at birth, which regrew sparsely after ritual shaving at 1 week of age. They were nearly devoid of normal eyebrows and eyelashes, but their axillary and pubic hair was normal. Affected males had normal beard hair, but no hair on their arms or legs. Wajid et al. (2007) examined 6 affected individuals from a large consanguineous Pakistani family with hypotrichosis of varying severity. All affected children were born without hair. After ritual shaving at approximately 3 weeks of age, sparse and coarse hair growth occurred that was sometimes accompanied by itching, redness, and roughness of the scalp. Fragile hairs were present in all affected individuals. Comparison of the clinical findings in the 4 male patients revealed marked variability that was not age-dependent in terms of severity: 2 boys, ages 5 and 7 years, had a relatively mild phenotype, sparing the eyebrows and lashes; a 17-year-old boy had follicular hyperkeratosis, erythema, and scaling affecting the scalp, eyebrows, and eyelashes; and the most severely affected individual was almost completely without hair at 13 years of age. Hair shafts from affected males showed tapered broken ends in addition to monilethrix-like nodes. All affected individuals had normal teeth, nails, and sweating, and their skin was otherwise normal with no papular lesions on the limbs and no palmoplantar keratoderma. Despite the marked variation in severity, Wajid et al. (2007) stated that the clinical findings were most consistent with a diagnosis of localized autosomal recessive hypotrichosis. - Monilethrix-like Congenital Hypotrichosis Hanhart (1955) reported a sister and brother with hypotrichosis who were born of first-cousin Swiss parents. At 21 years of age, the proband had dark brown hair that was partly normal and partly made up of thin, rough hairs that were broken off at different lengths; microscopic examination showed the characteristic regular 'spindles' of monilethrix. Keratosis follicularis was present on her occipital scalp and neck. Her axillary and pubic hair were also affected, and again only part of the hair was involved. She was also reported to be intellectually impaired. Her 37-year-old brother had similar hair with extensive balding, but 2 other sibs had normal hair, and the brother had 3 daughters with normal hair. Salamon and Schnyder (1962) later examined the parents and found no monilethrix-like hairs or keratosis follicularis; they also reported that the proband had a 3-year-old daughter with normal hair. Shimomura et al. (2006) studied a Japanese girl with congenital hypotrichosis who had short, dry, brittle, and lusterless scalp hairs, most of them emerging from keratotic follicular papules and breaking easily. Her eyebrows were also sparse, whereas her eyelashes were spared; nails and teeth were normal. At 7 months of age, her hair shafts showed no abnormalities under light microscopy, but scanning electron microscopy (SEM) revealed that the thickness of the shaft varied in some parts, resulting in nodes of normal thickness and abnormally thin internodes without regular periodicity. Breaks in the hair shaft always occurred at internodes, which at higher magnification were seen to have longitudinal ridges. Distal portions of some hairs were tapered and kept their cuticular scales, whereas others showed roughly broken bundles of cortical fibers. At 2 years of age, the patient had long terminal hairs which looked normal even by SEM, but short broken hairs were also present which showed the same abnormalities as previously observed, features resembling those of moniliform hair seen in monilethrix (158000). Schaffer et al. (2006) described 3 sibs of Iraqi and Iranian Jewish descent with monilethrix-like congenital hypotrichosis. The proband was a 2-year-old girl who was born with sparse, stubbly hair and a complete lack of eyebrows and eyelashes, who subsequently developed coarse, short, brittle hairs over most of the scalp, appearing as stubble and 'black dots' clinically. The hair growth was accompanied by numerous follicular papules on the scalp, associated with mild erythema, a variable degree of keratosis, and severe pruritus. She had no palmoplantar keratoderma or hypohidrosis, other skin lesions, or abnormalities of the teeth or nails. Her 4-month-old affected fraternal twin brothers were born with scattered, patchy areas of dark stubble on the scalp. Neither twin had eyebrow hairs; 1 had sparse eyelashes. All 3 sibs had crusting erosions of the scalp in the neonatal period that subsequently healed and did not recur. Light microscopy of hairs from the proband revealed an uneven, undulating diameter, and some areas appeared as separate elliptical nodal fragments with tapered ends. Many hairs displayed trichoschisis characterized by rounded, frayed ends, whereas other hairs showed bent shafts or longitudinal twisting suggestive of pili torti. Scalp biopsy of the proband at 18 months of age showed a normal density of terminal anagen hair follicles but with a markedly irregular structure, including 2 or 3 hair follicles converging in a single ostium. The formation of dilated 'blebs' was evident in the hair shafts of some follicles. There was an irregular boundary between the inner root sheath and the hair shaft, and the cortex of the shafts was distorted in appearance. Some hair shafts exhibited a jagged shape and fragmentation. The interfollicular epidermis was slightly hyperplastic with focal parakeratosis. Zlotogorski et al. (2006) studied 12 Jewish families of Iraqi, Iranian, and Moroccan descent who had early-onset generalized scalp alopecia within the first days of life, with a 'black dots' appearance. Follicular hyperkeratotic papules on the scalp, accompanied by erythema, scaling, dryness, and pruritus were also noted in infancy. Improvement in hair growth was documented towards the end of the second year of life, with patchy or widespread alopecia, especially of the posterior scalp. Hairs in general were short and brittle, but some reached a length of 10 to 20 cm. Two or 3 hair follicles infrequently converged in a single ostium. Eyebrows and eyelashes were sparse, with no body hair, decreased axillary hair, and sparing of pubic hair. Hyperkeratotic papules were most common on the lower posterior scalp and nape of neck, with a variable number of papules on the extensor surfaces of the upper arm and thigh and periumbilical area. Nails, teeth, and sweating were normal. The common hair abnormality was the elliptical node typical of monilethrix. Other occasionally seen hair abnormalities included pili torti, trichoschisis, trichorrhexis nodosa-like defects, and tapered hairs.
Kljuic et al. (2003) identified an identical homozygous 5-kb deletion within the DSG4 gene (607892.0001) in affected individuals from 2 Pakistani families with localized autosomal recessive hypotrichosis (LAH).
In 6 affected members of a large consanguineous ... Kljuic et al. (2003) identified an identical homozygous 5-kb deletion within the DSG4 gene (607892.0001) in affected individuals from 2 Pakistani families with localized autosomal recessive hypotrichosis (LAH). In 6 affected members of a large consanguineous Pakistani family with hypotrichosis, Wajid et al. (2007) identified homozygosity for a 1-bp deletion in the DSG4 gene (607892.0002). - Monilethrix-like Congenital Hypotrichosis In a Japanese girl with monilethrix-like congenital hypotrichosis, who was negative for mutation in the 3 keratin genes known to cause autosomal dominant monilethrix (158000), Shimomura et al. (2006) identified compound heterozygosity for mutations in the DSG4 gene (607892.0003-607892.0004). The authors suggested that LAH and monilethrix overlap and should not be regarded independently. In a 2-year-old girl of Iraqi and Iranian Jewish descent, who had monilethrix-like congenital hypotrichosis and was negative for mutation in the 3 keratin genes known to cause autosomal dominant monilethrix, Schaffer et al. (2006) identified compound heterozygosity for mutations in the DSG4 gene (607892.0005-607892.0006). Her affected fraternal twin brothers were also compound heterozygotes for the mutations. Schaffer et al. (2006) stated that these cases expanded the LAH phenotype to include monilethrix-like hairs and cutaneous fragility of the scalp in the neonatal period. In 7 Iraqi Jewish patients with monilethrix-like congenital hypotrichosis mapping to a gene cluster on chromosome 18q, Zlotogorski et al. (2006) sequenced the candidate gene DSG4 and identified homozygosity for a missense mutation (607892.0007). Subsequently, compound heterozygosity for 3 additional mutations were detected, including a splice site mutation and a 1-bp deletion in patients of Iranian descent (607892.0008 and 607892.0009, respectively) and a nonsense mutation in patients of Moroccan descent (607892.0010). Zlotogorski et al. (2006) suggested that the lack of classical hair shaft beading in previously reported LAH1 patients might be explained by the different mutations involved or by a different genetic background, but also noted that in some patients beading may be very scarce and may be overlooked unless dermatoscopic examination is performed to identify the distorted monilethric short hairs. Zlotogorski et al. (2006) concluded that despite the lack of microscopic hair shaft findings in LAH, there is considerable clinical overlap between LAH and patients with monilethrix-like congenital hypotrichosis.