Harlequin-type ichthyosis is a genetic disorder which results in thickened skin over nearly the Synonyms, Harlequin ichthyosis, hyosis fetalis, keratosis diffusa fetalis, harlequin fetus ichthyosis congenita gravior. Harlequin Autosomal recessive congenital ichthyosis (ARCI) encompasses several forms of nonsyndromic ichthyosis. Although most neonates with ARCI. German, kongenitale Ichthyose, Ichthyosis kongenital, Ichthyosis congenita, Ichthyosis Spanish, Ictiosis congénita, ictiosis congénita, SAI, ictiosis congénita .

Author: Juzahn JoJosida
Country: Sao Tome and Principe
Language: English (Spanish)
Genre: Travel
Published (Last): 10 October 2009
Pages: 139
PDF File Size: 19.50 Mb
ePub File Size: 20.60 Mb
ISBN: 974-6-16655-874-2
Downloads: 39102
Price: Free* [*Free Regsitration Required]
Uploader: Gagul

Harlequin ichthyosis is a rare severe form of congenital ichthyosis, which may be fatal. The neonate is encased in an ‘armor’ of thick scale plates separated by deep fissures. There is bilateral ectropion and eclabium, and the nose and ears are flattened and appear rudimentary.

Constricting bands around the extremities can restrict movement and cause idtiosis necrosis. As the skin barrier is severely compromised, neonates are more prone to sepsis, dehydration, and impaired thermoregulation.

Treatment with oral retinoids encourages shedding of the grossly thickened skin. Babies who survive into infancy and beyond develop skin changes resembling severe nonbullous congenital ichthyosiform ictiosks see summary by Rajpopat et al. For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive congenital ichthyosis, see ARCI1 Goldsmith agreed with the distinctness of this entity from lamellar ichthyosis.

It carries a more grave prognosis Shelmire, The baby is usually of low birth weight for dates and, as a rule, dies under 1 week of age. Plaques, measuring up to 4 or 5 cm on a side, have a diamond-like configuration resembling the suit of a harlequin clown.

Tonofibrils are fibrillar structural proteins in keratinocytes which, although already present in dividing basal cells, are formed in increasing amounts by the differentiating cells. They are the morphologic equivalent of the biochemically well-characterized prekeratin and precursors of the alpha-keratin of horn cells. Four genetic disorders of keratinization are known to ictioosis a structural defect of tonofibrils Anton-Lamprecht, The infants were covered with an enormous horny shell, similar to armor, with deep creases which fragmented the hard surface into large polygonal plates.

The limbs remained in rigid semiflexion. The nose ictipsis external ear were hidden in the keratotic layer.

Ichthyosis – Wikipedia

Severe ectropion and eclabion were present. All 4 sibs were born prematurely. Two were alive at birth but 1 died soon after delivery and the other 4 days after delivery. Lawlor presented an experience suggesting that harlequin fetus may be a severe form of nonbullous ichthyosiform erythroderma. All except 1 previously reported harlequin fetus died during the first few weeks of life. Lawlor described an infant who survived to 2 and a half years, progressing to the picture of nonbullous ichthyosiform erythroderma.

Temtamy described a family with 3 affected sibs and first-cousin parents; the eyes were bulging in the infants and a typically characteristic feature was markedly hypoplastic fingers. It appeared that the tight skin did not permit growth of the fingers. The parents were second cousins; of 4 previously born children, 2 had the harlequin syndrome and died at birth.

Arnold and Anton-Lamprecht concluded that prenatal diagnosis of the ichthyosis congenita group cannot be based on disturbance of keratinization because of the late onset of normal keratinization. Biochemical and ultrastructural abnormalities have suggested genetic heterogeneity and division into 3 subtypes of harlequin ichthyosis Dale et al. From the photographs taken in the neonatal period, they looked very similar; however, whereas one died in the first day or so of life, the second required assisted ventilation for 5 days but survived thereafter and was alive at the age of almost 6 years at the time of report.


Investigation at 15 months for failure to thrive indicated protein malnutrition as a consequence of enormous losses of protein in desquamated skin. Institution of a very high intake of protein led congneita satisfactory growth and development. The first sib was cared for with the frequent application of paraffin ointment to the whole body and oral etretinate. The skin gradually softened. Improvement in the skin around the mouth allowed the infant to suck from a bottle by day 4 and to breastfeed by the age of 1 week.

The range of movement in all the limbs improved and the fingers and toes assumed a more normal shape. The baby was discharged home at the age of 51 days.

Although his weight gain was poor, with weight remaining below the third percentile, at the age of 18 months he was alert, able to make cooing and babbling sounds, and had normal hearing and vision. He had good neck control, ictioeis could not crawl or sit up unaided.

At the age of 22 months, he was admitted to hospital where he was found to have blood cultures positive for Staphylococcus aureus and died 24 hours after admission. The second sib succumbed to infection complicated by disseminated intravascular coagulation at the age of 44 days.

Iictiosis second sib had developed areas of ischemia and gangrene on bony prominences and the tips of the fingers and toes. Culican and Custer reported the successful use of an Apligraf human skin equivalent for repair of bilateral cicatricial ectropion in a patient with harlequin ichthyosis. Evidence for recessive inheritance of this disorder was provided by several reports Bustamente and Tejeda, ; Ictiosia, ; Lattuada and Parker, congenifa Smith, ; Thomson and Wakeley,and by parental consanguinity Edmonds and Ichiosis, Chorionic villus karyotyping of the fetus had revealed a nonmosaic chromosome 2 trisomy, whereas postnatal peripheral blood karyotype was normal, indicating trisomic rescue.

The authors proposed that a gene for this condition may lie within the deleted region. Using SNP chip technology and homozygosity mapping, Kelsell et al. By sequencing of the ABCA12 gene, which maps within the critical region of chromosome 2q35 for harlequin ichthyosis, Kelsell et al.

Since the epidermis in harlequin ichthyosis displays abnormal lamellar granule formation, Kelsell et al. In 5 patients with harlequin ichthyosis from 4 unrelated families, Akiyama et al. The authors noted that the vast majority of ABCA12 mutations associated with harlequin ichthyosis are predicted to result in a truncated protein, although 1 patient was homozygous for a missense mutation In a Caucasian British child born congenit severe ichthyosiform erythroderma, in whom Kelsell et al.

No CST6 mutations were detected in this group, which comprised type 1 and type 2 harlequin ichthyosis patients. Akiyama reviewed mutations congenitz the ABCA12 gene and stated that a total of 56 mutations had been reported in 66 ARCI families, including 48 with harlequin ichthyosis HI10 with lamellar ichthyosis LIand 8 with ichthyosis of the congenital ichthyosiform erythroderma CIE type. Most of the mutations in HI patients were truncation mutations, and homozygosity or compound heterozygosity for truncating mutations in ABCA12 always resulted in the HI phenotype.

The disorder is inherited as a fully penetrant autosomal recessive and in general, its features are very similar to those of human harlequin ichthyosis. This region corresponds to the locus of the spontaneous harlequin ichthyosis ichq mouse mutation.


Mice that were homozygous for 2 null alleles displayed a hyperplastic, hyperkeratotic epidermis and abnormal hair follicles, and died between 5 and 12 days of age. In the ichq Cst6-null mouse, Zeeuwen et al.

Analysis of stratum corneum proteins revealed a strong decrease of soluble loricrin monomers in icyiosis extracts of ichq mice, although normal levels of loricrin were present in the stratum granulosum and stratum corneum.


This suggested a premature or enhanced crosslinking of loricrin monomers in ichq mice by transglutaminase-3 TGM3; Increased levels of TGM3 were processed into activated and kD subunits, compared to wildtype mice.

They further proposed that disturbance of this protease-antiprotease balance may cause increased enzyme activity of TGM3 that could explain the observed abnormal cornification. Waring pointed to an early mention of a harlequin fetus in the diary of the Reverend O. ABCA12 mutations and autosomal recessive congenital ichthyosis: Regional difference in expression of characteristic abnormality of harlequin ichthyosis in affected fetuses.

Mutations in lipid transporter ABCA12 in harlequin ichthyosis and functional recovery by corrective gene transfer.

Electron microscopy in the early diagnosis of genetic disorders of the skin. Problems in prenatal diagnosis of the ichthyosis congenita group. Prenatal diagnosis of harlequin fetus.


Ichthyosis fetalis gravis in two successive pregnancies. Trisomic rescue causing reduction to homozygosity for a novel ABCA12 mutation in harlequin ichthyosis. Repair of cicatricial ectropion in an infant with harlequin ichthyosis using engineered human skin. Heterogeneity in harlequin ichthyosis, an inborn error of epidermal congenitw Ichthyosis congenita fetalis, severe type harlequin fetus.

Prenatal diagnosis of harlequin ichthyosis. Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis. Ichthyosis congenita with unusual complications. Progress of a harlequin fetus to nonbullous ichthyosiform erythroderma. Ichthyosis, lamellar exfoliative type.

Revised nomenclature and classification of inherited ichthyoses: Management and follow-up of harlequin siblings. Lamellar ichthyosis of the newborn. Influence of nutrition on growth and development of a long-surviving harlequin fetus. Lamellar exfoliation of newborn. A case of intrauterine ichthyosis.

Conbenita novo deletion of chromosome 18q in a baby with harlequin ichthyosis. ABCA12 is the major harlequin ichthyosis gene. Harlequin foetus in four siblings.

Early mention of a harlequin fetus in America. A number sign is used with this entry because of evidence that the harlequin fetus type of congenital ichthyosis, here congenitq ARCI4B, is caused by homozygous or compound heterozygous mutation in the ABCA12 gene on chromosome 2q A bonus to all MIMmatch users is the option to sign up for updates on new gene-phenotype relationships.

Clinical Synopsis Toggle Dropdown. Phenotypic Series Toggle Dropdown. CC ]. Prenatal Diagnosis Blanchet-Bardon et al. Jumana Al-Aama cngenita updated: TEXT A number sign is used with this entry because of evidence that the harlequin fetus type of congenital ichthyosis, here symbolized ARCI4B, is caused by homozygous or compound heterozygous mutation in the ABCA12 gene on chromosome 2q OMIM is intended for use primarily by physicians and other professionals concerned with genetic disorders, by genetics researchers, and by advanced students in science and medicine.