Adult presentation of X‐linked Conradi‐Hünermann‐Happle syndrome

Abstract

Conradi-Hünermann-Happle syndrome, or X-linked Dominant Chondrodysplasia Punctata Type 2 (CDPX2), is a genodermatosis caused by mutations in EBP. While typically lethal in males, females with CDPX2 generally manifest by infancy or childhood with variable features including congenital ichthyosiform erythroderma, chondrodysplasia punctata, asymmetric shortening of the long bones, and cataracts. We present a 36-year-old female with short stature, rhizomelic and asymmetric limb shortening, severe scoliosis, a sectorial cataract, and no family history of CDPX2. Whole exome sequencing (WES) revealed a p.Arg63del mutation in EBP, and biochemical studies confirmed a diagnosis of CDPX2. Short stature in combination with ichthyosis or alopecia, cataracts, and limb shortening in an adult should prompt consideration of a diagnosis of CDPX2. As is the case with many genetic syndromes, the hallmark features of CDPX2 in pediatric patients are not readily identifiable in adults. This case demonstrates the utility of WES as a diagnostic tool in the evaluation of adults with genetic disorders.

Human Cholesterol Biosynthesis Defects

“…The pattern and then resolution of skin scaling as well as its histological profile is a differentiating diagnostic feature for CDPX2 compared to CHILD syndrome. Diagnosis of CDPX2 in adulthood can be difficult due to the childhood resolution of the characteristic skin lesions and epiphyseal stippling [86]; however, a combination of cutaneous manifestations, asymmetric limb reduction and cataracts (found in 65% of patients) is a good suggestion of this condition for further investigation [86]. CDPX2 presents with characteristic facial features including frontal bossing, midface hypoplasia and flat nasal bridge [74,81].…”

Cutaneous Mosaicism and Dermatoses with Mosaic Pattern: Review

“…Katarakt gibi göz anomalileri de bu sendroma eşlik edebilir. 13,32 e e) ) M MI ID DA AS S s se en nd dr ro om mu u ( (m mi ik kr ro of ft ta al lm mi i v ve e l li in ne ee er r d de er ri i d de ef fe ek kt tl le er ri i) ): HCCS geninde mutasyon sonucu görülen ve mikroftalmi, dermal aplazi ve sklerokornea ile seyreden bir sendromdur. Sıklıkla yüz-boyun bölgesindeki Blaschko çizgilerini izleyen eritemli, telenjiektatik ve aplazik lezyonlarla seyreder.…”

Structural and functional foot disorders in patients with genodermatoses: a single-centre, retrospective chart review

“…Palmoplantar keratodermas (PPKs), a heterogeneous group of cornification diseases, are characterised by a thickened epidermis on the palms and soles [3]. Some syndromic generalised diseases of cornification cause symptoms such as abnormal second and third toes (Refsum disease), pes cavus (ichthyosis follicularis, atrichia, and photophobia [IFAP]), or limb shortening (Conradi-Hünermann-Happle syndrome) [4,5]. However, little data are available on foot deformities in rare genodermatoses; as such, foot deformities and their consequences in patients with genodermatoses are often neglected in clinical practice, reducing patients' quality of life [6].…”