Occipital horn syndrome

Occipital horn syndrome
Classification and external resources
ICD-10	E83.0
OMIM	304150
DiseasesDB	33413

Occipital horn syndrome (OHS), formerly considered a variant of Ehlers-Danlos syndrome,^[1] is an X-linked recessive connective tissue disorder. It is caused by a deficiency in the transport of the essential mineral copper, associated with mutations in the ATP7A gene.^[2]^[3] Only about 2/3 of children with OHS are thought to have genetically inherited the disorder; the other 1/3 do not have the disease in their family history. Since the disorder is X-linked recessive the disease affects more males. This is because they do not have a second X chromosome, unlike females, so essentially are lacking the 'backup' copy with proper function. Females are much more likely to be carriers only. For a female to be affected they must carry two defective X chromosomes, not just one.^[4] The disorder is considered a milder variant of Menkes disease.^[5]

Characteristics 1
Treatment 2
See also 3
References 4
External links 5

Characteristics

It is characterized by a deficiency in biliary copper excretion that causes deformations in the skeleton. These include projections on the back of the skull (parasagittal bone exostoses arising from the occipital bone—the so-called "occipital horns") as well as deformities of the elbow, radial head dislocation, hammer-shaped lateral ends of the clavicles, and abnormalities of the hips and pelvis.^[1] OHS presents in early to middle childhood.^[4] Children may present with features such as:

Normal/slightly delayed intelligence
Long neck, high arched palate, long face, high forehead
Looseness of skin and "double jointed"
Inguinal Hernias
Twisting of blood vessels
Bladder diverticula
Dysautonomia—inability to regulate parts of the nervous system
Chronic Diarrhea
Coarse hair

Treatment

Courses of treatment for children with is dependent upon the severity of their case. Children with OHS often receive physical and occupational therapy.^[4] They may require a feeding tube to supplement nourishment if they are not growing enough. In an attempt to improve the neurological condition (seizures) copper histidine or copper chloride injections can be given early in the child’s life. However, copper histidine injections have been shown ineffective in studies of copper metabolic-connective tissue disorders such as OHS.^[6]

References

^ ^a ^b Online 'Mendelian Inheritance in Man' (OMIM) 304150
^ Scheiber, Ivo; Dringen, Ralf; Mercer, Julian F. B. (2013). "Chapter 11. Copper: Effects of Deficiency and Overload". In Astrid Sigel, Helmut Sigel and Roland K. O. Sigel. Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences 13. Springer. pp. 359–387.
^ Tang J, Robertson S, Lem KE, Godwin SC, Kaler SG (November 2006). "Functional copper transport explains neurologic sparing in occipital horn syndrome". Genet. Med. 8 (11): 711–8.
^ ^a ^b ^c Horn Syndrome, 9 August 2004.
^ Kennerson ML, Nicholson GA, Kaler SG, et al. (March 2010). "Missense mutations in the copper transporter gene ATP7A cause X-linked distal hereditary motor neuropathy". Am. J. Hum. Genet. 86 (3): 343–52.
^ Kodama, H., C. Fujisima, W. Bhadhprasit. (November 2010). . Brain & Development.

External links

GeneReviews/NCBI/NIH/UW entry on ATP7A-Related Copper Transport Disorders
Occipital horn syndrome at NIH's Office of Rare Diseases

Sex linkage: 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's disease Mucopolysaccharidosis: Hunter syndrome Purine-pyrimidine metabolism: Lesch–Nyhan syndrome Mineral: Menkes disease/Occipital horn syndrome

Nervous system	X-linked mental retardation: Coffin–Lowry syndrome MASA syndrome X-linked alpha thalassemia mental retardation syndrome Siderius X-linked mental retardation syndrome 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's 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 error of metal metabolism (E83, 275)

Transition metal

high:	Primary iron overload disorder: Hemochromatosis/HFE1 Juvenile/HFE2 HFE3 African iron overload/HFE4 Aceruloplasminemia Atransferrinemia Hemosiderosis

deficiency:	Iron deficiency

high:	Copper toxicity Wilson's disease

deficiency:	Copper deficiency Menkes disease/Occipital horn syndrome

high:	Zinc toxicity

deficiency:	Acrodermatitis enteropathica

Electrolyte

Na⁺ and K⁺

see

PO₄³⁻

high:	Hyperphosphatemia

deficiency:	Hypophosphatemia alkaline phosphatase Hypophosphatasia

Mg²⁺

high:	Hypermagnesemia

deficiency:	Hypomagnesemia

Ca²⁺

high:	Hypercalcaemia Milk-alkali syndrome (Burnett's) Calcinosis (Calciphylaxis, Calcinosis cutis) Calcification (Metastatic calcification, Dystrophic calcification) Familial hypocalciuric hypercalcemia

deficiency:	Hypocalcaemia Osteomalacia Pseudohypoparathyroidism (Albright's hereditary osteodystrophy) Pseudopseudohypoparathyroidism

Index of nutrition

Description	Fats Sugars

Disease

Treatment	Drugs

Occipital horn syndrome