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PubMed This is a summary of 7 peer-reviewed journal articles Updated
Pediatrics

Recognizing the Physical Signs of Microform HPE

At a Glance

Microform holoprosencephaly (mHPE) is diagnosed by midline facial clues rather than brain abnormalities. The most recognizable sign is a single upper front tooth (SMMCI). Because the face and pituitary gland develop together, these signs indicate a need to monitor hormone levels and growth.

When a child is diagnosed with microform holoprosencephaly (mHPE), the diagnosis is usually based on physical signs rather than brain abnormalities. It is important to remember that in mHPE, these facial features exist even though the brain has successfully divided into two hemispheres [1]. These signs are not evidence of brain damage; instead, they are “midline clues” that tell us about how the face and certain glands formed during early development [2].

The Single Middle Tooth (SMMCI)

One of the most common and recognizable signs of mHPE is a solitary median maxillary central incisor (SMMCI) [3]. In most people, there are two separate front teeth in the upper jaw. In children with SMMCI, there is only one single tooth, and it is located exactly in the center of the mouth [2][4].

This applies to both primary (baby) and secondary (adult) teeth—meaning one baby tooth will eventually fall out and be replaced by one single adult tooth [3].

  • Who notices it?: Because this is a dental feature, pediatricians or pediatric dentists are often the first to identify it during routine checkups [3].
  • Why it matters: The upper jaw and the teeth form along the midline of the face. Having a single middle tooth is a signal to doctors to look closer at other midline structures, such as the pituitary gland [4].

Closely Spaced Eyes (Hypotelorism)

Another frequent sign is ocular hypotelorism, which is the medical term for eyes that are positioned closer together than average [5][6]. This is a subtle feature that may not be obvious to everyone, but it is measured by doctors during a physical exam to help confirm a diagnosis within the holoprosencephaly spectrum [5].

Other Midline Features

Because mHPE affects the development of the center of the face, doctors look for several other minor signs:

  • Nasal Shape: The nose may have a very narrow or sharp bridge, or there may be general nasal airway narrowing [6].
  • The Philtrum: This is the small groove between the bottom of the nose and the top of the lip. In some children with mHPE, this groove may be flat or missing [6].
  • Clefts: Sometimes a small cleft (a gap or opening) may be present exactly in the middle of the lip or the roof of the mouth [6].

Sense of Smell (Anosmia)

Some children within the holoprosencephaly spectrum have a reduced or absent sense of smell, known as anosmia [7]. This happens because the olfactory bulbs, which sit near the midline of the brain, may be underdeveloped. This is important to monitor as it can impact a child’s appetite and safety (for instance, the inability to smell smoke) [7].

Why We Monitor These Signs

It can be confusing to have a diagnosis based on a tooth or the position of the eyes. However, the reason doctors track these physical signs is that the face and the pituitary gland develop from the same embryonic tissues [4][2].

The pituitary gland is the “master gland” that controls growth and metabolism. Even if the brain is structurally normal, these facial “clues” suggest that the pituitary gland might need a check-up to ensure it is producing enough hormones for your child to grow and develop properly [2]. While the features themselves are permanent, they do not prevent your child from having a healthy, happy life with the right monitoring [1].

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Common questions in this guide

What is a solitary median maxillary central incisor (SMMCI)?
SMMCI stands for solitary median maxillary central incisor. It is a condition where a child has only one single front tooth located exactly in the center of the upper jaw, instead of the usual two. It is a key indicator of microform holoprosencephaly.
Why do doctors monitor the pituitary gland in children with mHPE?
The center of the face and the pituitary gland develop from the same embryonic tissues. Facial signs of mHPE serve as clues that the pituitary gland may need to be checked to ensure it is producing enough hormones for your child's growth and metabolism.
What other facial features are associated with microform holoprosencephaly?
Other common physical signs include closely spaced eyes (hypotelorism), a narrow or sharp nasal bridge, a flat groove above the upper lip (philtrum), or a small midline cleft in the lip or roof of the mouth. Some children may also lack a sense of smell.
Does microform holoprosencephaly mean my child has brain damage?
Unlike more severe forms of the condition, children with microform holoprosencephaly have a brain that has successfully divided into two hemispheres. The diagnosis is based on physical facial clues, not structural brain damage.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Can you confirm if my child has a solitary median maxillary central incisor (SMMCI)?
  2. 2.Since the face and the pituitary gland develop together, should we check my child's growth and thyroid hormone levels?
  3. 3.Are there any other minor midline features you notice, such as the shape of the nose or the philtrum?
  4. 4.Does my child need to see a pediatric dentist or an orthodontist for specialized dental care?
  5. 5.How do these physical signs help us understand my child's overall health and development?

Questions For You

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References

References (7)
  1. 1

    Holoprosencephaly: a survey of the entity, with embryology and fetal imaging.

    Winter TC, Kennedy AM, Woodward PJ

    Radiographics : a review publication of the Radiological Society of North America, Inc 2015; (35(1)):275-90 doi:10.1148/rg.351140040.

    PMID: 25590404
  2. 2

    Solitary median maxillary central incisor, holoprosencephaly and congenital nasal pyriform aperture stenosis in a premature infant: case report.

    Ilhan O, Pekcevik Y, Akbay S, et al.

    Archivos argentinos de pediatria 2018; (116(1)):e130-e134 doi:10.5546/aap.2018.eng.e130.

    PMID: 29333838
  3. 3

    Solitary median maxillary central incisor syndrome caused by 22q11.2 microdeletion.

    Shima H, Miura A, Kawashima S, et al.

    Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology 2025; (34(1)):54-59 doi:10.1297/cpe.2024-0024.

    PMID: 39777126
  4. 4

    The solitary median maxillary central incisor (SMMCI) syndrome: Associations, prenatal diagnosis, and outcomes.

    Garcia Rodriguez R, Garcia Cruz L, Novoa Medina Y, et al.

    Prenatal diagnosis 2019; (39(6)):415-419 doi:10.1002/pd.5451.

    PMID: 30900264
  5. 5

    Duplicated distal phalanx of thumb or hallux in trisomy 13: A recurrent feature in a series of 42 fetuses.

    Létard P, Guimiot F, Dupont C, et al.

    American journal of medical genetics. Part A 2018; (176(11)):2325-2330 doi:10.1002/ajmg.a.40505.

    PMID: 30328679
  6. 6

    Microform holoprosencephaly with bilateral congenital elbow dislocation; increasing the phenotypic spectrum of Steinfeld syndrome.

    Jones GE, Robertson L, Maniyar A, et al.

    American journal of medical genetics. Part A 2016; (170(3)):754-9 doi:10.1002/ajmg.a.37511.

    PMID: 26728615
  7. 7

    Biallelic variants in ZNF526 cause a severe neurodevelopmental disorder with microcephaly, bilateral cataract, epilepsy and simplified gyration.

    Dentici ML, Alesi V, Quinodoz M, et al.

    Journal of medical genetics 2022; (59(3)):262-269 doi:10.1136/jmedgenet-2020-107430.

    PMID: 33397746

This page provides educational information about the physical signs of microform holoprosencephaly. It is not a substitute for professional medical evaluation. Always consult a pediatrician or specialist for an accurate diagnosis and monitoring plan for your child.

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