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Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome(MDHLO)

MedGen UID:
1794190
Concept ID:
C5561980
Disease or Syndrome
Synonyms: MDHLO; MUSCULAR DYSTROPHY, CONGENITAL HEARING LOSS, AND OVARIAN INSUFFICIENCY SYNDROME
 
Gene (location): GGPS1 (1q42.3)
 
Monarch Initiative: MONDO:0859189
OMIM®: 619518

Definition

Muscular dystrophy, congenital hearing loss, and ovarian insufficiency syndrome (MDHLO) is an autosomal recessive systemic disorder characterized by progressive muscle weakness, sensorineural hearing loss, and endocrine abnormalities, mainly primary amenorrhea due to ovarian insufficiency. Features of the disorder appear soon after birth, although endocrine anomalies are not noted until puberty. The severity of the phenotype is variable: some patients may lose ambulation and have significant respiratory insufficiency, whereas others retain the ability to walk (Foley et al., 2020). [from OMIM]

Clinical features

From HPO
Female infertility
MedGen UID:
5795
Concept ID:
C0021361
Pathologic Function
Infertility in a woman.
Premature ovarian insufficiency
MedGen UID:
9963
Concept ID:
C0025322
Disease or Syndrome
Amenorrhea due to loss of ovarian function before the age of 40. Primary ovarian inssuficiency (POI) is a state of female hypergonadotropic hypogonadism. It can manifest as primary amenorrhea with onset before menarche or secondary amenorrhea.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
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).
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Poor suck
MedGen UID:
324693
Concept ID:
C1837142
Finding
An inadequate sucking reflex, resulting in the difficult of newborns to be breast-fed.
Sensorineural hearing loss disorder
MedGen UID:
9164
Concept ID:
C0018784
Disease or Syndrome
A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.
Loss of ambulation
MedGen UID:
332305
Concept ID:
C1836843
Finding
Inability to walk in a person who previous had the ability to walk.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Progressive muscle weakness
MedGen UID:
68704
Concept ID:
C0240421
Finding
Centrally nucleated skeletal muscle fibers
MedGen UID:
330782
Concept ID:
C1842170
Finding
An abnormality in which the nuclei of sarcomeres take on an abnormally central localization (or in which this feature is found in an increased proportion of muscle cells).
Rimmed vacuoles
MedGen UID:
340089
Concept ID:
C1853932
Finding
Presence of abnormal vacuoles (membrane-bound organelles) in the sarcolemma. On histological staining with hematoxylin and eosin, rimmed vacuoles are popcorn-like clear vacuoles with a densely blue rim. The vacuoles are often associated with cytoplasmic and occasionally intranuclear eosinophilic inclusions.
Skeletal muscle autophagosome accumulation
MedGen UID:
1814214
Concept ID:
C5676640
Finding
Abnormal accumulation of autophagosomes in skeletal muscle tissue.
Respiratory insufficiency
MedGen UID:
11197
Concept ID:
C0035229
Pathologic Function
Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.
Reduced forced vital capacity
MedGen UID:
337630
Concept ID:
C1846678
Finding
An abnormal reduction in the amount of air a person can expel following maximal inspiration.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Weak cry
MedGen UID:
65892
Concept ID:
C0234860
Finding
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Mitochondrial hypertrophy
MedGen UID:
1740956
Concept ID:
C5435767
Finding
Enlargement of mitochondria. Mitochondrial hypertrophy is not discernible by light microscopy. By electron microscopy (EM), hypertrophic mitochondria have normal cristae and normal matrix density. In contrast, swollen mitochondria display swollen cristae and irregular matrix densities in EM.

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