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Macrocephaly, dysmorphic facies, and psychomotor retardation(MDFPMR)

MedGen UID:
934733
Concept ID:
C4310766
Disease or Syndrome
Synonym: MDFPMR
 
Gene (location): HERC1 (15q22.31)
 
Monarch Initiative: MONDO:0014863
OMIM®: 617011

Definition

Macrocephaly, dysmorphic facies, and psychomotor retardation (MDFPMR) is an autosomal recessive neurodevelopmental disorder characterized by large head and somatic overgrowth apparent at birth followed by global developmental delay. Affected individuals have characteristic dysmorphic facial features and persistently large head, but increased birth weight normalizes with age. Additional neurologic features, including seizures, hypotonia, and gait ataxia, may also occur. Patients show severe intellectual impairment (summary by Ortega-Recalde et al., 2015). [from OMIM]

Clinical features

From HPO
Arachnodactyly
MedGen UID:
2047
Concept ID:
C0003706
Congenital Abnormality
Abnormally long and slender fingers (spider fingers).
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Large hands
MedGen UID:
98097
Concept ID:
C0426870
Finding
Long foot
MedGen UID:
154365
Concept ID:
C0576225
Finding
Increased back to front length of the foot.
Tall stature
MedGen UID:
69137
Concept ID:
C0241240
Finding
A height above that which is expected according to age and gender norms.
Disproportionate tall stature
MedGen UID:
323048
Concept ID:
C1836996
Finding
A tall and slim body build with increased arm span to height ratio (>1.05) and a reduced upper-to-lower segment ratio (<0.85), i.e., unusually long arms and legs. The extremities as well as the hands and feet are unusually slim.
Large for gestational age
MedGen UID:
341215
Concept ID:
C1848395
Finding
The term large for gestational age applies to babies whose birth weight lies above the 90th percentile for that gestational age.
Macrotia
MedGen UID:
488785
Concept ID:
C0152421
Congenital Abnormality
Median longitudinal ear length greater than two standard deviations above the mean and median ear width greater than two standard deviations above the mean (objective); or, apparent increase in length and width of the pinna (subjective).
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Communicating hydrocephalus
MedGen UID:
1058
Concept ID:
C0009451
Disease or Syndrome
A form of hydrocephalus in which there is no visible obstruction to the flow of the cerebrospinal fluid between the ventricles and subarachnoid space.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Megalencephaly
MedGen UID:
65141
Concept ID:
C0221355
Congenital Abnormality
Diffuse enlargement of the entire cerebral hemispheres leading to macrocephaly (with or without overlying cortical dysplasia).
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Cerebellar atrophy
MedGen UID:
196624
Concept ID:
C0740279
Disease or Syndrome
Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event.
Gait ataxia
MedGen UID:
155642
Concept ID:
C0751837
Sign or Symptom
A type of ataxia characterized by the impairment of the ability to coordinate the movements required for normal walking. Gait ataxia is characteirzed by a wide-based staggering gait with a tendency to fall.
Thick corpus callosum
MedGen UID:
371993
Concept ID:
C1835194
Finding
Increased vertical dimension of the corpus callosum. This feature can be visualized by sagittal sections on magnetic resonance tomography imaging of the brain.
Absent speech
MedGen UID:
340737
Concept ID:
C1854882
Finding
Complete lack of development of speech and language abilities.
Ventriculomegaly
MedGen UID:
480553
Concept ID:
C3278923
Finding
An increase in size of the ventricular system of the brain.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Cerebral cortical atrophy
MedGen UID:
1646740
Concept ID:
C4551583
Disease or Syndrome
Atrophy of the cortex of the cerebrum.
Kyphosis
MedGen UID:
44042
Concept ID:
C0022821
Anatomical Abnormality
Exaggerated anterior convexity of the thoracic vertebral column.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
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.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
The presence of an abnormal lateral curvature of the spine.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
Bilateral bulging of the lateral frontal bone prominences with relative sparing of the midline.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Malar flattening
MedGen UID:
347616
Concept ID:
C1858085
Finding
Underdevelopment of the malar prominence of the jugal bone (zygomatic bone in mammals), appreciated in profile, frontal view, and/or by palpation.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
High palate
MedGen UID:
66814
Concept ID:
C0240635
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).
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Upslanted palpebral fissure
MedGen UID:
98390
Concept ID:
C0423109
Finding
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.
Downslanted palpebral fissures
MedGen UID:
98391
Concept ID:
C0423110
Finding
The palpebral fissure inclination is more than two standard deviations below the mean.
Sparse eyebrow
MedGen UID:
371332
Concept ID:
C1832446
Finding
Decreased density/number of eyebrow hairs.
Triangular face
MedGen UID:
324383
Concept ID:
C1835884
Finding
Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin.
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Long neck
MedGen UID:
333409
Concept ID:
C1839816
Finding
Increased inferior-superior length of the neck.
Prominent nasal bridge
MedGen UID:
343051
Concept ID:
C1854113
Finding
Anterior positioning of the nasal root in comparison to the usual positioning for age.
Proptosis
MedGen UID:
41917
Concept ID:
C0015300
Disease or Syndrome
An eye that is protruding anterior to the plane of the face to a greater extent than is typical.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Professional guidelines

PubMed

Muhsin E, Basak G, Banu D, Alper G, Mustafa S
J Mol Neurosci 2022 Jan;72(1):149-157. Epub 2021 Aug 12 doi: 10.1007/s12031-021-01897-5. PMID: 34386909

Recent clinical studies

Etiology

Muhsin E, Basak G, Banu D, Alper G, Mustafa S
J Mol Neurosci 2022 Jan;72(1):149-157. Epub 2021 Aug 12 doi: 10.1007/s12031-021-01897-5. PMID: 34386909
Marczak-Hałupka A, Kalina MA, Tańska A, Chrzanowska KH
Pediatr Endocrinol Diabetes Metab 2015;20(3):101-6. doi: 10.18544/PEDM-20.03.0009. PMID: 26615046

Diagnosis

Muhsin E, Basak G, Banu D, Alper G, Mustafa S
J Mol Neurosci 2022 Jan;72(1):149-157. Epub 2021 Aug 12 doi: 10.1007/s12031-021-01897-5. PMID: 34386909
Bi W, Glass IA, Muzny DM, Gibbs RA, Eng CM, Yang Y, Sun A
Am J Med Genet A 2016 Aug;170(8):2181-5. Epub 2016 May 12 doi: 10.1002/ajmg.a.37727. PMID: 27170158
Pierson TM, Zimmerman RA, Tennekoon GI, Bönnemann CG
Neuropediatrics 2008 Apr;39(2):123-7. doi: 10.1055/s-2008-1081218. PMID: 18671190
Pivnick EK, Angle B, Kaufman RA, Hall BD, Pitukcheewanont P, Hersh JH, Fowlkes JL, Sanders LP, O'Brien JM, Carroll GS, Gunther WM, Morrow HG, Burghen GA, Ward JC
Am J Med Genet 2000 Jan 17;90(2):131-40. PMID: 10607952
Young TL, Ziylan S, Schaffer DB
J Pediatr Ophthalmol Strabismus 1993 Jan-Feb;30(1):48-52. doi: 10.3928/0191-3913-19930101-12. PMID: 8455127

Prognosis

Kárteszi J, Kosztolányi G, Czakó M, Hadzsiev K, Morava É
Clin Dysmorphol 2006 Jan;15(1):29-31. doi: 10.1097/01.mcd.0000175605.10844.3e. PMID: 16317304
Boente MC, Carrero-Valenzuela RD, Frontini MV, Asial RA
Eur J Dermatol 2001 Sep-Oct;11(5):453-7. PMID: 11525956
Orstavik KH, Strømme P, Ek J, Torvik A, Skjeldal OH
J Med Genet 1997 Oct;34(10):849-51. doi: 10.1136/jmg.34.10.849. PMID: 9350820Free PMC Article

Clinical prediction guides

Baena N, Monk D, Aguilera C, Fraga MF, Fernández AF, Gabau E, Corripio R, Capdevila N, Trujillo JP, Ruiz A, Guitart M
Clin Epigenetics 2024 May 7;16(1):62. doi: 10.1186/s13148-024-01652-8. PMID: 38715103Free PMC Article
Muhsin E, Basak G, Banu D, Alper G, Mustafa S
J Mol Neurosci 2022 Jan;72(1):149-157. Epub 2021 Aug 12 doi: 10.1007/s12031-021-01897-5. PMID: 34386909
Mubungu G, Lukute G, Makay P, Songo C, Lukusa P, Devriendt K, Lumaka A
Am J Med Genet A 2020 Jul;182(7):1572-1575. Epub 2020 May 14 doi: 10.1002/ajmg.a.61617. PMID: 32406590
Bi W, Glass IA, Muzny DM, Gibbs RA, Eng CM, Yang Y, Sun A
Am J Med Genet A 2016 Aug;170(8):2181-5. Epub 2016 May 12 doi: 10.1002/ajmg.a.37727. PMID: 27170158
Pavone P, Praticò AD, Campisi C, Falsaperla R
BMJ Case Rep 2016 Apr 18;2016:10.1136/bcr-2016-214388. doi: 10.1136/bcr-2016-214388. PMID: 27090543Free PMC Article

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