Conradi–Hünermann syndrome

(Redirected from Conradi syndrome) Rare X-linked form of chondrodysplasia punctata Medical condition

Conradi–Hünermann syndrome
Other names	"Conradi–Hünermann–Happle syndrome", "Happle syndrome," and "X-linked dominant chondrodysplasia punctata"
Specialty	Medical genetics

Conradi–Hünermann syndrome is a rare type of chondrodysplasia punctata. It is associated with the EBP gene and affects between one in 100,000 and one in 200,000 babies.

Signs and symptoms

Possible signs and symptoms may include

Growth deficiency
Low nasal bridge
Flat face
Down-slanting space between eyelids
Cataracts
Asymmetric limb shortness
Joint shortening or spasms
Frequent scoliosis
Frequent kyphosis
Abnormal redness of the skin
Thick scales on infant skin
Large skin pores
Flaky skin
Sparse hair
Coarse hair
Bald spots/alopecia
Ichthyosis

Genetics

Conradi–Hünermann syndrome is a form of chondrodysplasia punctata, a group of rare genetic disorders of skeletal development involving abnormal accumulations of calcium salts within the growing ends of long bones. Conradi–Hünermann syndrome is commonly associated with mild to moderate growth deficiency, disproportionate shortening of long bones, particularly those of the upper arms and the thigh bones, short stature, and/or curvature of the spine. In rare cases, intellectual disability may also be present. While evidence suggests that Conradi–Hünermann syndrome predominantly occurs in females and is usually inherited as an X-linked dominant trait, rare cases in which males were affected have also been reported.

The genetics of Conradi–Hünermann syndrome have perplexed medical geneticists, pediatricians and dermatologists for some time, but a number of perplexing features of the genetics of the syndrome have now been resolved, including the fact that the disease is caused by mutations in a gene, and these mutations are simple substitutions, deletions or insertions and are therefore not "unstable". Scientists are still trying to understand exactly where the mutation occurs so that they can correct it.

Diagnosis

An important test to confirm a diagnosis of Conradi–Hünermann syndrome is evaluating the plasma for elevated levels of a substance known as sterols. Mutations of the EBP gene result in the accumulation of sterols in the plasma and certain tissues of the body. Sterol levels are measured by gas chromatography-mass spectrometry.

Screening

Genetic screening for Conradi–Hünermann syndrome via the EBP Gene is offered by multiple providers.

Treatment

Treatment can involve operations to lengthen the leg bones, which involves many visits to the hospital. Other symptoms can be treated with medicine or surgery. Most female patients with the syndrome can live a long and normal life, while males have only survived in rare cases.

History

It is also known as Happle's syndrome, after the German Physician, Rudolf Happle (b. 1938), who wrote a series of papers about the disease in 1976. The name Conradi–Hünermann Syndrome is named for Erich Conradi (1882–1968), and Carl (Karl) Hünermann (1904–1978), both are German Physicians.

References

Thomas Bernard Fitzpatrick; Irwin M. Freedberg (2003). Fitzpatrick's Dermatology in General Medicine. ISBN 978-0-07-138076-8.
^ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L.; Joseph L. Jorizzo; Ronald P. Rapini (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
Ausavarat S, Tanpaiboon P, Tongkobpetch S, Suphapeetiporn K, Shotelersuk V (2008). "Two novel EBP mutations in Conradi–Hünermann–Happle syndrome". Eur J Dermatol. 18 (4): 391–3. doi:10.1684/ejd.2008.0433 (inactive 1 November 2024). PMID 18573709.{{cite journal}}: CS1 maint: DOI inactive as of November 2024 (link)
Steijlen PM, van Geel M, Vreeburg M, et al. (December 2007). "Novel EBP gene mutations in Conradi–Hünermann–Happle syndrome". Br. J. Dermatol. 157 (6): 1225–9. doi:10.1111/j.1365-2133.2007.08254.x. PMID 17949453. S2CID 25890696.
National Organization for Rare Disorders. "Conradi Hünermann Syndrome - NORD (National Organization for Rare Disorders)". National Organization for Rare Disorders. Retrieved 2018-03-01.
National Center for Biotechnology Information (2016-08-17). "Clinical test for Chondrodysplasia punctata 2 X-linked dominant Offered by Laboratory Genetic Metabolic Diseases". National Center for Biotechnology Information. Retrieved 2018-03-01.
National Center for Biotechnology Information (2017-12-04). "Clinical test for Chondrodysplasia punctata 2 X-linked dominant offered by PreventionGenetics". National Center for Biotechnology Information. Retrieved 2018-03-01.

External links

Classification	D ICD-10: Q77.3 ICD-9-CM: 756.59 OMIM: 302960 DiseasesDB: 32527 SNOMED CT: 398719004

GeneReviews/NCBI/NIH/UW entry on Chondrodysplasia Punctata 2, X-Linked, Conradi–Hünermann Syndrome, Happle Syndrome

Osteochondrodysplasias

Osteodysplasia/
osteodystrophy

Diaphysis	Camurati–Engelmann disease
Metaphysis	Metaphyseal dysplasia Jansen's metaphyseal chondrodysplasia Schmid metaphyseal chondrodysplasia
Epiphysis	Spondyloepiphyseal dysplasia congenita Multiple epiphyseal dysplasia Otospondylomegaepiphyseal dysplasia
Osteosclerosis	Raine syndrome Osteopoikilosis Osteopetrosis
Other/ungrouped	FLNB Boomerang dysplasia Opsismodysplasia Polyostotic fibrous dysplasia McCune–Albright syndrome

Chondrodysplasia/
chondrodystrophy
(including dwarfism)

Osteochondroma

osteochondromatosis
- Hereditary multiple exostoses

Chondroma/enchondroma

enchondromatosis
- Ollier disease
- Maffucci syndrome

Growth factor receptor

FGFR2:	Antley–Bixler syndrome
FGFR3:	Achondroplasia Hypochondroplasia Thanatophoric dysplasia

COL2A1 collagen disease

SLC26A2 sulfation defect

Chondrodysplasia punctata

Other dwarfism

X-linked disorders

X-linked recessive
Immune	Chronic granulomatous disease (CYBB) Wiskott–Aldrich syndrome X-linked severe combined immunodeficiency X-linked agammaglobulinemia Hyper-IgM syndrome type 1 IPEX X-linked lymphoproliferative disease Properdin deficiency
Hematologic	Haemophilia A Haemophilia B X-linked sideroblastic anemia
Endocrine	Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy KAL1 Kallmann syndrome X-linked adrenal hypoplasia congenita
Metabolic	Amino acid: Ornithine transcarbamylase deficiency Oculocerebrorenal syndrome Dyslipidemia: Adrenoleukodystrophy Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency Pyruvate dehydrogenase deficiency Danon disease/glycogen storage disease Type IIb Lipid storage disorder: Fabry disease Mucopolysaccharidosis: Hunter syndrome Purine–pyrimidine metabolism: Lesch–Nyhan syndrome Mineral: Menkes disease/Occipital horn syndrome
Nervous system	X-linked intellectual disability: Coffin–Lowry syndrome MASA syndrome Alpha-thalassemia mental retardation syndrome PHF8 Eye disorders: Color blindness (red and green, but not blue) Ocular albinism (1) Norrie disease Choroideremia Other: Charcot–Marie–Tooth disease (CMTX2-3) Pelizaeus–Merzbacher disease SMAX2
Skin and related tissue	Dyskeratosis congenita Hypohidrotic ectodermal dysplasia (EDA) X-linked ichthyosis X-linked endothelial corneal dystrophy
Neuromuscular	Becker muscular dystrophy/Duchenne Centronuclear myopathy (MTM1) Conradi–Hünermann syndrome Emery–Dreifuss muscular dystrophy 1
Urologic	Alport syndrome Dent's disease X-linked nephrogenic diabetes insipidus
Bone/tooth	AMELX Amelogenesis imperfecta
No primary system	Barth syndrome McLeod syndrome Smith–Fineman–Myers syndrome Simpson–Golabi–Behmel syndrome Mohr–Tranebjærg syndrome Nasodigitoacoustic syndrome

X-linked dominant
X-linked hypophosphatemia Focal dermal hypoplasia Fragile X syndrome Aicardi syndrome Incontinentia pigmenti Rett syndrome CHILD syndrome Lujan–Fryns syndrome Orofaciodigital syndrome 1 Craniofrontonasal dysplasia

Inborn errors of steroid metabolism

Mevalonate
pathway

HMG-CoA lyase deficiency

To cholesterol

desmosterol path: Desmosterolosis

Steroids

Corticosteroid
(including CAH)

aldosterone: Glucocorticoid remediable aldosteronism

Sex steroid

To androgens	17α-Hydroxylase deficiency 17,20-Lyase deficiency Cytochrome b₅ deficiency 3β-Hydroxysteroid dehydrogenase deficiency 17β-Hydroxysteroid dehydrogenase deficiency 5α-reductase 2 deficiency Pseudovaginal perineoscrotal hypospadias
To estrogens	Aromatase deficiency Aromatase excess syndrome

Other

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