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Hennekam-Beemer syndrome

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: CUTANEOUS MASTOCYTOSIS, CONDUCTIVE HEARING LOSS AND MICROTIA; Mastocytosis cutaneous with short stature conductive hearing loss and microtia; Skin mastocytosis hearing loss microcephaly mild dysmorphic features and severe mental retardation
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
Concept ID:
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Monarch Initiative: MONDO:0009569
OMIM®: 248910
Orphanet: ORPHA2135


A rare multiple congenital anomalies syndrome characterized by cutaneous mastocytosis, microcephaly, microtia and/or hearing loss, hypotonia and skeletal anomalies (e.g. clinodactyly, camptodactyly, scoliosis). Additional common features are short stature, intellectual disability and difficulties. Facial dysmorphism may include upslanted palpebral fissures, highly arched palate and micrognathia. Rarely, seizures and asymmetrically small feet have been reported. [from ORDO]

Clinical features

From HPO
Short foot
MedGen UID:
Concept ID:
A measured foot length that is more than 2 SD below the mean for a newborn of 27 - 41 weeks gestation, or foot that is less than the 3rd centile for individuals from birth to 16 years of age (objective). Alternatively, a foot that appears disproportionately short (subjective).
Clinodactyly of the 5th finger
MedGen UID:
Concept ID:
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Short stature
MedGen UID:
Concept ID:
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Feeding difficulties
MedGen UID:
Concept ID:
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Conductive hearing impairment
MedGen UID:
Concept ID:
Disease or Syndrome
An abnormality of vibrational conductance of sound to the inner ear leading to impairment of sensory perception of sound.
MedGen UID:
Concept ID:
Congenital Abnormality
Underdevelopment of the external ear.
Intellectual disability
MedGen UID:
Concept ID:
Mental or Behavioral Dysfunction
Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.
MedGen UID:
Concept ID:
Congenital Abnormality
Developmental hypoplasia of the mandible.
MedGen UID:
Concept ID:
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
MedGen UID:
Concept ID:
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Joint contracture of the 5th finger
MedGen UID:
Concept ID:
Anatomical Abnormality
Chronic loss of joint motion in the 5th finger due to structural changes in non-bony tissue. The term camptodactyly of the 5th finger is used if the distal and/or proximal interphalangeal joints are affected.
MedGen UID:
Concept ID:
Head circumference below 2 standard deviations below the mean for age and gender.
Cutaneous mastocytosis
MedGen UID:
Concept ID:
Mastocytosis, or mast cell disease, is a heterogeneous group of clinical disorders characterized by the abnormal accumulation of mast cells in various tissues, especially in the skin and hematopoietic organs. Mastocytosis usually appears in infancy or early adulthood. In most pediatric cases, the disease is limited to the skin, but it can be associated with systemic symptoms due to the release of mediators from mast cells, even when there is no systemic infiltration. It usually has a good prognosis, with substantial improvement or spontaneous resolution before puberty. In rare cases, the disease may remain active through adolescence as a systemic adult mastocytosis. Cutaneous mastocytosis is characterized by macules, papules, nodules, or diffuse infiltration of the skin, often associated with localized hyperpigmentation. Gentle rubbing of the lesions induces histamine release from mechanically activated mast cells, causing local wheals, erythema, and often pruritus, a phenomenon termed the 'Darier sign.' In contrast to childhood-onset mastocytosis, adult-onset mastocytosis often persists for the lifetime of the patient and is also more likely to be a severe and systemic disease involving numerous organs. In some cases, it is associated with a clonal hematologic non-mast-cell lineage disease, such as a myelodysplastic or myeloproliferative disorder. Adult-onset mastocytosis can also lead to the rare mast cell leukemia, which carries a high risk of mortality (summary by Bodemer et al., 2010 and Kambe et al., 2010).
High palate
MedGen UID:
Concept ID:
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Upslanted palpebral fissure
MedGen UID:
Concept ID:
The palpebral fissure inclination is more than two standard deviations above the mean for age (objective); or, the inclination of the palpebral fissure is greater than typical for age.
MedGen UID:
Concept ID:
Congenital Abnormality
Epicanthus is a condition in which a fold of skin stretches from the upper to the lower eyelid, partially covering the inner canthus. Usher (1935) noted that epicanthus is a normal finding in the fetus of all races. Epicanthus also occurs in association with hereditary ptosis (110100).
Underdeveloped nasal alae
MedGen UID:
Concept ID:
Congenital Abnormality
Thinned, deficient, or excessively arched ala nasi.
Wide nasal bridge
MedGen UID:
Concept ID:
Increased breadth of the nasal bridge (and with it, the nasal root).
Dermatographic urticaria
MedGen UID:
Concept ID:
Disease or Syndrome
An exaggerated whealing tendency when the skin is stroked, that is, formation of red, itchy bumps and lines on the skin as a result of pressure on the skin (for instance, stroking the skin with a pen or tongue depressor).

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHennekam-Beemer syndrome

Professional guidelines


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Recent clinical studies


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Koster MJ, Samec MJ, Warrington KJ
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J Allergy Clin Immunol 2017 Aug;140(2):349-355. doi: 10.1016/j.jaci.2017.06.007. PMID: 28780942
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Cells 2021 Jun 28;10(7) doi: 10.3390/cells10071613. PMID: 34203240Free PMC Article
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Košutova P, Mikolka P
Physiol Res 2021 Dec 30;70(Suppl4):S567-S583. doi: 10.33549/physiolres.934767. PMID: 35199544Free PMC Article
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Clinical prediction guides

Darden DB, Brakenridge SC, Efron PA, Ghita GL, Fenner BP, Kelly LS, Mohr AM, Moldawer LL, Moore FA
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Recent systematic reviews

Sales C, Calma AD
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