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Neurodevelopmental disorder with dysmorphic facies and distal limb anomalies(NEDDFL)

MedGen UID:
1627464
Concept ID:
C4540327
Disease or Syndrome
Synonyms: NEDDFL; NEURODEVELOPMENTAL DISORDER WITH DYSMORPHIC FACIES AND DISTAL LIMB ANOMALIES
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
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).
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
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 heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): BPTF (17q24.2)
 
Monarch Initiative: MONDO:0060596
OMIM®: 617755
Orphanet: ORPHA528084

Definition

NEDDFL is a neurodevelopmental disorder characterized by delayed psychomotor development and intellectual disability, poor growth with small head size, dysmorphic facial features, and mild abnormalities of the hands and feet (summary by Stankiewicz et al., 2017). [from OMIM]

Clinical features

From HPO
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.
Small hand
MedGen UID:
108279
Concept ID:
C0575802
Finding
Disproportionately small hand.
Overlapping toe
MedGen UID:
182531
Concept ID:
C0920299
Anatomical Abnormality
Describes a foot digit resting on the dorsal surface of an adjacent digit when the foot is at rest. Initially clawing may be dynamic and only noticeable on walking. Over time the plantar plate tears, subluxation occurs at the metatarsophalangeal joint (MTPJ), and the deformity becomes permanent.
Sandal gap
MedGen UID:
374376
Concept ID:
C1840069
Finding
A widely spaced gap between the first toe (the great toe) and the second toe.
Clinodactyly of the 5th finger
MedGen UID:
340456
Concept ID:
C1850049
Congenital Abnormality
Clinodactyly refers to a bending or curvature of the fifth finger in the radial direction (i.e., towards the 4th finger).
Slender finger
MedGen UID:
387832
Concept ID:
C1857482
Finding
Fingers that are disproportionately narrow (reduced girth) for the hand/foot size or build of the individual.
Broad hallux
MedGen UID:
401165
Concept ID:
C1867131
Finding
Visible increase in width of the hallux without an increase in the dorso-ventral dimension.
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).
Delayed speech and language development
MedGen UID:
105318
Concept ID:
C0454644
Finding
A degree of language development that is significantly below the norm for a child of a specified age.
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.
Abnormal cerebral white matter morphology
MedGen UID:
181756
Concept ID:
C0948163
Pathologic Function
An abnormality of the cerebral white matter.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
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.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Microcephaly
MedGen UID:
1644158
Concept ID:
C4551563
Finding
Head circumference below 2 standard deviations below the mean for age and gender.
Narrow mouth
MedGen UID:
44435
Concept ID:
C0026034
Congenital Abnormality
Distance between the commissures of the mouth more than 2 SD below the mean. Alternatively, an apparently decreased width of the oral aperture (subjective).
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.
Short palpebral fissure
MedGen UID:
98067
Concept ID:
C0423112
Finding
Distance between the medial and lateral canthi is more than 2 SD below the mean for age (objective); or, apparently reduced length of the palpebral fissures.
Prominent nose
MedGen UID:
98423
Concept ID:
C0426415
Finding
Distance between subnasale and pronasale more than two standard deviations above the mean, or alternatively, an apparently increased anterior protrusion of the nasal tip.
Broad nasal tip
MedGen UID:
98424
Concept ID:
C0426429
Finding
Increase in width of the nasal tip.
Epicanthus
MedGen UID:
151862
Concept ID:
C0678230
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).
Long nasal bridge
MedGen UID:
331712
Concept ID:
C1834320
Finding
Increased superior-inferior length of the nasal bridge, which is the saddle-shaped area that includes the nasal root and the lateral aspects of the nose.
Broad eyebrow
MedGen UID:
344657
Concept ID:
C1856121
Finding
Regional increase in the width (height) of the eyebrow.
Thin upper lip vermilion
MedGen UID:
355352
Concept ID:
C1865017
Finding
Height of the vermilion of the upper lip in the midline more than 2 SD below the mean. Alternatively, an apparently reduced height of the vermilion of the upper lip in the frontal view (subjective).
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).
Esodeviation
MedGen UID:
1641033
Concept ID:
C4551734
Disease or Syndrome
A manifest or latent ocular deviation in which one or both eyes tends to deviate nasally.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVNeurodevelopmental disorder with dysmorphic facies and distal limb anomalies

Professional guidelines

PubMed

Sepulveda W, Dezerega V, Horvath E, Aracena M
J Ultrasound Med 1999 Oct;18(10):707-10. doi: 10.7863/jum.1999.18.10.707. PMID: 10511304

Recent clinical studies

Etiology

Tamhankar PM, Vasudevan L, Bansal V, Menon SR, Gawde HM, D'Souza A, Babu S, Kondurkar S, Adhia R, Das DK
Eur J Med Genet 2015 Aug;58(8):392-9. Epub 2015 Jun 24 doi: 10.1016/j.ejmg.2015.06.002. PMID: 26117586
Shah N, Gupta YK, Ghose S
Int J Paediatr Dent 2004 Jan;14(1):78-85. doi: 10.1111/j.1365-263x.2004.00471.x. PMID: 14706033
Davis C, Samarakkody U
J Paediatr Child Health 2002 Jun;38(3):318-20. doi: 10.1046/j.1440-1754.2002.00820.x. PMID: 12047706
Sepulveda W, Dezerega V, Horvath E, Aracena M
J Ultrasound Med 1999 Oct;18(10):707-10. doi: 10.7863/jum.1999.18.10.707. PMID: 10511304

Diagnosis

Glinton KE, Hurst ACE, Bowling KM, Cristian I, Haynes D, Adstamongkonkul D, Schnappauf O, Beck DB, Brewer C, Parikh AS, Shinde DN, Donaldson A, Brautbar A, Koene S, van Haeringen A, Piton A, Capri Y, Furlan M, Gardella E, Møller RS, van de Beek I, Zuurbier L, Lakeman P, Bayat A, Martinez J, Signer R, Torring PM, Engelund MB, Gripp KW, Amlie-Wolf L, Henderson LB, Midro AT, Tarasów E, Stasiewicz-Jarocka B, Moskal-Jasinska D, Vos P, Boschann F, Stoltenburg C, Puk O, Mero IL, Lossius K, Mignot C, Keren B, Acosta Guio JC, Briceño I, Gomez A, Yang Y, Stankiewicz P
Am J Med Genet A 2021 May;185(5):1366-1378. Epub 2021 Jan 31 doi: 10.1002/ajmg.a.62102. PMID: 33522091Free PMC Article
Conrad S, Demurger F, Moradkhani K, Pichon O, Le Caignec C, Pascal C, Thomas C, Bayart S, Perlat A, Dubourg C, Jaillard S, Nizon M
Am J Med Genet A 2019 Jun;179(6):993-1000. Epub 2019 Mar 19 doi: 10.1002/ajmg.a.61113. PMID: 30888095
Burnside RD, Molinari S, Botti C, Brooks SS, Chung WK, Mehta L, Schwartz S, Papenhausen P
Am J Med Genet A 2018 Sep;176(9):1956-1963. Epub 2018 Aug 8 doi: 10.1002/ajmg.a.40355. PMID: 30088856
Sepulveda W, Dezerega V, Horvath E, Aracena M
J Ultrasound Med 1999 Oct;18(10):707-10. doi: 10.7863/jum.1999.18.10.707. PMID: 10511304
Pascual-Castroviejo I, Roche C, Martinez-Bermejo A, Arcas J, Lopez-Martin V, Tendero A, Esquiroz JL, Pascual-Pascual SI
Brain Dev 1998 Jan;20(1):36-43. doi: 10.1016/s0387-7604(97)00097-1. PMID: 9533559

Therapy

Wu W, Chen R
Mol Genet Genomic Med 2023 Jan;11(1):e2066. Epub 2022 Sep 24 doi: 10.1002/mgg3.2066. PMID: 36153657Free PMC Article

Prognosis

Cingöz S, Soydemir D, Öner TÖ, Karaca E, Özden B, Kurul SH, Bayram E; University of Washington Center for Mendelian Genomics, Coe BP, Nickerson DA, Eichler EE
Eur J Med Genet 2022 Jun;65(6):104497. Epub 2022 Apr 14 doi: 10.1016/j.ejmg.2022.104497. PMID: 35430327Free PMC Article
Alessandri JL, Cuillier F, Malan V, Brayer C, Grondard M, Jacquemot-Dekkak L, Kieffer-Traversier M, Pierre F, Laurain C, Samperiz S, Tiran-Rajaofera I, Ramful D
Am J Med Genet A 2014 Mar;164A(3):648-54. Epub 2013 Dec 19 doi: 10.1002/ajmg.a.36323. PMID: 24357154
Shah N, Gupta YK, Ghose S
Int J Paediatr Dent 2004 Jan;14(1):78-85. doi: 10.1111/j.1365-263x.2004.00471.x. PMID: 14706033
Davis C, Samarakkody U
J Paediatr Child Health 2002 Jun;38(3):318-20. doi: 10.1046/j.1440-1754.2002.00820.x. PMID: 12047706

Clinical prediction guides

Cingöz S, Soydemir D, Öner TÖ, Karaca E, Özden B, Kurul SH, Bayram E; University of Washington Center for Mendelian Genomics, Coe BP, Nickerson DA, Eichler EE
Eur J Med Genet 2022 Jun;65(6):104497. Epub 2022 Apr 14 doi: 10.1016/j.ejmg.2022.104497. PMID: 35430327Free PMC Article
Conrad S, Demurger F, Moradkhani K, Pichon O, Le Caignec C, Pascal C, Thomas C, Bayart S, Perlat A, Dubourg C, Jaillard S, Nizon M
Am J Med Genet A 2019 Jun;179(6):993-1000. Epub 2019 Mar 19 doi: 10.1002/ajmg.a.61113. PMID: 30888095
Burnside RD, Molinari S, Botti C, Brooks SS, Chung WK, Mehta L, Schwartz S, Papenhausen P
Am J Med Genet A 2018 Sep;176(9):1956-1963. Epub 2018 Aug 8 doi: 10.1002/ajmg.a.40355. PMID: 30088856
Alkuraya FS, Lin AE, Irons MB, Kimonis VE
Am J Med Genet A 2005 Jan 15;132A(2):226-30. doi: 10.1002/ajmg.a.30423. PMID: 15580636
Pascual-Castroviejo I, Roche C, Martinez-Bermejo A, Arcas J, Lopez-Martin V, Tendero A, Esquiroz JL, Pascual-Pascual SI
Brain Dev 1998 Jan;20(1):36-43. doi: 10.1016/s0387-7604(97)00097-1. PMID: 9533559

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