Acute skin manifestations of Conradi-Huenermann syndrome in a male adult

Crovato, F.

doi:10.1001/archderm.121.8.1064

Cited by 7 publications

(9 citation statements)

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“…CHH is predominantly lethal in male embryos carrying a germline EBP mutation, although a number of cases of surviving affected males have been described [Crovato and Rebora, ; Hochman and Fee, ; De Raeve et al, ; Tronnier et al, ; Omobono and Goetsch, ; Happle, ]. For many of these cases, molecular analysis has not been performed or reported, but these males demonstrated features similar to those of affected females.…”

Section: Introductionmentioning

confidence: 99%

An unusual phenotype of X‐linked developmental delay and extreme behavioral difficulties associated with a mutation in the EBP gene

Hartill

Tysoe

Manning

et al. 2014

American J of Med Genetics Pt A

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We report on a family in which four males over three generations are affected with X-linked recessive developmental delay, learning difficulties, severe behavioral difficulties and mild dysmorphic features. Plasma sterol analysis in three of the four affected males demonstrated increased concentrations of 8-dehydrocholesterol (8-DHC) and cholest-8(9)-enol. All four affected males had a novel hemizygous missense mutation, p.W47R (c.139T>C), in EBP. Functional studies showed raised levels of cholest-8(9)-enol in patient's cultured fibroblast cells, which were suppressed when the cells were incubated with simvastatin. EBP encodes 3β-hydroxysteroid-delta8, delta7-isomerase, a key enzyme involved in the cholesterol biosynthesis pathway. Mutations in EBP have previously been associated with Conradi-Hunermann-Happle syndrome (CHH), an X-linked dominant disorder characterized by skeletal dysplasia, skin, and ocular abnormalities, which is usually lethal in males. Four previous reports describe X-linked recessive multiple anomaly syndromes associated with non-mosaic EBP mutations in males, two at the same amino acid position, p.W47C. This phenotype has previously been described as "MEND" syndrome (male EBP disorder with neurological defects). The family reported herein represent either a novel phenotype, or an expansion of the MEND phenotype, characterized by extreme behavioral difficulties and a scarcity of structural anomalies. Simvastatin therapy is being evaluated in two males from this family.

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Section: Introductionmentioning

confidence: 99%

An unusual phenotype of X‐linked developmental delay and extreme behavioral difficulties associated with a mutation in the EBP gene

Hartill

Tysoe

Manning

et al. 2014

American J of Med Genetics Pt A

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“…X‐linked dominant Conradi‐Hunermann‐Happle syndrome (CDPX2; MIM 302960) is a rare chondrodysplasia punctata primarily affecting females. CDPX2 is presumed lethal in males [Wettke‐Schafer and Kantner, 1983], although about 10 affected males have been reported [Crovato and Rebora, 1985; Hochman and Fee, 1987; Sillevis Smitt et al, 1987; De Raeve et al, 1989; Tronnier et al, 1992; Omobono and Goetsch, 1993; Happle, 1995; Sutphen et al, 1995; Aughton et al, 2001]. CDPX2 is a postsqualene cholesterol biosynthetic disorder due to 3‐β‐hydroxysteroid‐Δ8,Δ7‐isomerase deficiency caused by mutations in the emopamil binding protein ( EBP ) gene [Braverman et al, 1999].…”

Section: Introductionmentioning

confidence: 99%

Improved outcomes in patients with osteogenic sarcoma of the head and neck

Patel

Meyers

Huvos

et al. 2002

Cancer

154

133

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X‐linked dominant Conradi‐Hunermann‐Happle syndrome (CDPX2; MIM 302960) is a rare chondrodysplasia punctata primarily affecting females. CDPX2 is presumed lethal in males, although a few affected males have been reported. CDPX2 is a cholesterol biosynthetic disorder due to 3‐β‐hydroxysteroid‐Δ8,Δ7‐isomerase deficiency caused by mutations in the emopamil binding protein (EBP) gene. A 2.5‐year‐old Caucasian male was followed from the age of 6 weeks and noted to have significant developmental delay, hypotonia, seizures, and patchy hypopigmentation. Multiple congenital anomalies included a unilateral cataract, esotropia, crossed renal ectopia, stenotic ear canals, and failure to thrive, requiring G‐tube placement. Multiple minor anomalies and ptosis were noted. No skeletal asymmetry or chondrodysplasia punctata were noted on skeletal survey at 6 weeks and 13 months. An extensive genetic work‐up including cholesterol (126–176 mg/dl) and 7‐dehydrocholesterol was unrevealing. However, the levels of 8(9)‐cholestenol and 8‐dehydrocholesterol were mildly increased in plasma, which was confirmed in cultured fibroblasts. This prompted molecular analysis of the EBP gene, which revealed a novel hemizygous (nonmosaic) mutation in exon 2 (L18P). Two restriction digests were developed that confirmed this mutation in skin fibroblasts, blood, and buccal cells (all nonmosaic). We determined that the patient's mother (adopted) also has the L18P mutation enabling prenatal diagnosis of a normal male fetus. She has normal stature, no asymmetry, no cataracts at this time, and has a patch of hyperpigmentation on her chest best visualized on Woods lamp examination, characteristic of CDPX2. The mild maternal phenotype has been described previously. However, this nonmosaic missense mutation has resulted in a severe phenotype in her surviving son. © 2003 Wiley‐Liss, Inc.

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“…By way of exception, however, several male patients with CDPX2 have been documented. [6][7][8][9][10][11][12][13][14] Recently, there were a few reports about male patients with nonmosaic EBP (emopamil-binding protein) mutations and neurological and dysmorphic features being categorized as having a particular phenotypic variant of CHH syndrome. [15][16][17] We here describe a further case of CHH syndrome occurring in a boy with a postzygotic EBP mutation, review the literature and propose a new name for the nonmosaic phenotype with neurological symptoms in males (Table 1).…”

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confidence: 99%